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Early detection of breast cancer (BC) comprises two approaches: screening of asymptomatic women in a specified target population at risk (usually a target age range for women at average risk), and early diagnosis for women with BC signs and symptoms. Screening for BC is a key health intervention for early detection. While population-based screening programs have been implemented for age-selected women, the pivotal clinical trials have not addressed the global utility nor the improvement of screening performance by utilizing more refined parameters for patient eligibility, such as individualized risk stratification. In addition, with the exception of the subset of women known to carry germline pathogenetic mutations in (high- or moderately-penetrant) cancer predisposition genes, such as BRCA1 and BRCA2, there has been less success in outreach and service provision for the unaffected relatives of women found to carry a high-risk mutation (i.e., "cascade testing") as it is in these individuals for whom such actionable information can result in cancers (and/or cancer deaths) being averted. Moreover, even in the absence of clinical cancer genetics services, as is the case for the immediate and at least near-term in most countries globally, the capacity to stratify the risk of an individual to develop BC has existed for many years, is available for free online at various sites/platforms, and is increasingly being validated for non-Caucasian populations. Ultimately, a precision approach to BC screening is largely missing. In the present chapter, we aim to address the concept of risk-adapted screening of BC, in multiple facets, and understand if there is a value in the implementation of adapted screening strategies in selected women, outside the established screening prescriptions, in the terms of age-range, screening modality and schedules of imaging., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The phosphoinositide 3-kinase (PI3K) pathway plays a key role in cancer, influencing growth, proliferation, and survival of tumor cells. PIK3CA mutations are generally oncogenic and responsible for uncontrolled cellular growth. PI3K inhibitors (PI3Ki) can inhibit the PI3K/AKT/mTOR pathway, although burdened by not easily manageable toxicity. Among PI3Ki, alpelisib, a selective p110α inhibitor, is approved for the treatment of hormone receptor (HR)+/HER2- PIK3CA mutant metastatic breast cancer (BC) that has progressed to a first line endocrine therapy. PIK3CA mutations are also present in triple negative BC (TNBC) and HER2+ BC, although the role of PI3K inhibition is not well established in these subtypes. In this review, we go through the PI3K/AKT/mTOR pathway, describing most common mutations found in PI3K genes and how they can be detected. We describe the available biological and clinical evidence of PIK3CA mutations in breast cancers other than HR+/HER2-, summarizing clinical trials investigating PI3Ki in these subtypes.

Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers; however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 after neoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequently associated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorly understood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have been suggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behind HER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples. The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of this phenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specifically addressing HER2 loss are warranted., Competing Interests: Curigliano G received honoraria for consulting/advisory role/speaker bureau and/or travel funding from Roche, Lilly, Bristol-Myers Squibb, Pfizer, Novartis, and Seagen; Criscitiello C received honoraria for consulting/advisory role/speaker bureau from Novartis, Eli-Lilly, Pfizer, MSD, Seagen and Roche; Fusco N from Merck Sharp and Dohme (MSD), Boehringer Ingelheim, Novartis, AstraZeneca, and Daiichi Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2022.)

TPX-0046 is designed to overcome resistance to FDA approved RET inhibitors Selpercatinib and Pralsetinib. Early prediction of resistance mechanisms to investigational drugs may facilitate subsequent drug and trial designs. This study aims to predict potential mutations inducing resistance to TPX-0046. We conducted an in-silico analysis of TPX-0046 macrocyclic structure and predicted the binding mode on RET. We used as reference literary examples of resistance mechanisms to other macrocyclic inhibitors (Lorlatinib on ALK/ROS1) to construct RET secondary resistance mutations. We conducted docking simulations to evaluate impact of mutations on TPX-0046 binding. TPX-0046 binding mode on RET appears to not be influenced by Solventfront G810X mutation presence. Bulky Gatekeeper V804X mutations affect predicted TPX-0046 binding mode. Mutations in Beta 7 strand region L881F and xDFG S891L impair TPX-0046 docking. Our findings suggest that development of second generation RET inhibitors focused mainly on Solventfront G810X mutations granting resistance to selective RET inhibitors Selpercatinib and Pralsetinib. If these findings are confirmed by identification of Gatekeeper V804X mutations in patients progressing to TPX-0046, explanation of acquired resistance and loss of benefit will be easier These findings might accelerate development of third generation RET inhibitors, as well as clinical trial design in precision oncology settings., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Considering the rapid improvement of cancer drugs' efficacy and the discovery of new molecular targets, the formulation of therapeutical indications based on the multidisciplinary approach of MTB is becoming increasingly important for attributing the correct salience to the targets identified in a single patient. Nevertheless, one of the biggest stumbling blocks faced by MTBs is not the bare indication, but its implementation in the clinical practice. Indeed, administering the drug suggested by MTB deals with some relevant difficulties: the economical affordability and geographical accessibility represent some of the major limits in the patient's view, while bureaucracy and regulatory procedures are often a disincentive for the physicians. In this review, we explore the current literature reporting MTB experiences and precision medicine clinical trials, focusing on the challenges that authors face in applying their therapeutical indications. Furthermore, we analyze and discuss some of the solutions devised to overcome these difficulties to support the MTBs in finding the most suitable solution for their specific situation. In conclusion, we strongly encourage regulatory agencies and pharmaceutical companies to develop effective strategies with medical centers implementing MTBs to facilitate access to innovative drugs and thereby allow broader therapeutical opportunities to patients.

Introduction: Immunotherapy through the blockade of PD1-PDL1 axis has shown to improve outcomes in advanced and early triple negative breast cancer (TNBC). To further enhance immune-stimulation, and ultimately improve patient outcomes, a wide variety of next-generation immunotherapies (NGIO) is being developed for this disease., Areas Covered: In the present article, we discuss the immune landscape of TNBC and recapitulate the rationale and available clinical evidence of NGIO under early phase development for TNBC, highlighting challenges and opportunities in this emerging field of research., Expert Opinion: Multiple immunotherapeutic strategies beyond PD-(L)1 blockade have been tested for TNBC, including the targeting of further inhibitory checkpoints, the agonism of costimulatory molecules, the intratumoral administration of immunotherapies and cancer vaccines. Most of these strategies have demonstrated to be safe in early clinical trials, with some exhibiting early signs of antitumor activity. To optimally harness the potential of NGIO, a refined patient selection based on emerging immune biomarkers will be required, through an adaptation of immunotherapeutic strategies based on patient and tumor characteristics. More mature data from ongoing clinical trials, added to the progressively increasing knowledge on breast cancer immune landscape, will hopefully clarify the role of NGIO for the treatment of TNBC.

Antibody-drug conjugates (ADCs) and immunotherapy have prompted a revolution in the treatment of cancer. However, only a limited fraction of patients obtained a long-term benefit; consequently, combination studies have become a central focus of the current preclinical and clinical research in oncology. A strong biological rationale supports the investigation of combining ADCs with immunotherapy to overcome the occurrence of resistance and improve patient outcomes. ADCs interact with cancer and immune cells by eliciting mechanisms such as immunogenic cell death, antibody-dependent cell-mediated cytotoxicity and dendritic cell activation, ultimately providing potential synergism with immunotherapy. Indeed, ADCs induce tumor-specific adaptive immunity, increasing the infiltration of T cells into the tumor microenvironment, whereas immune-checkpoint inhibitors reinvigorate exhausted T cells, enhancing antitumor immune responses. In light of the promising preclinical data, several clinical trials are currently underway in multiple tumor types to evaluate the safety and activity of combination regimens. Initial evidence from early phase clinical trials has already reported encouraging signals. This review focuses on the combination of ADCs and immunotherapy, highlighting the key mechanisms underlying the synergistic effect and providing an overview of the available clinical evidence in solid tumors. In addition, opportunities to optimize the combination are explored, such as defining the optimal dose, balancing the risks and benefits of dose modifications, and the possibility of developing novel immunoconjugates., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cardiac amyloidosis is an infiltrative disorder caused by transthyretin or immunoglobulin free light-chain deposition, which determines clinical disease with similar phenotype but different time course, prognosis and therapy. Multimodality imaging is the cornerstone for disease diagnosis and management. Multimodality imaging has revolutionized the approach to the disease favoring its awareness and simplifying its diagnosis, especially in ATTR cardiac amyloidosis. This describes the different imaging tools, from the traditional to the more novel ones, and highlights the different approach in each different setting (prognosis, subtyping, prognosis, monitoring disease progression, and response to therapy)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen (Ag)-specific T-cell responses and potentially achieve long-term clinical benefit. However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technological advances regarding vaccine delivery platforms, tools for immunogenomic profiling, and Ag/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease-2019 pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the severe acute respiratory syndrome coronavirus 2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology., Competing Interests: Disclosure JC reports consulting/advisor fees or honoraria from: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GSK, Novartis, Eisai, Pfizer, Samsung Bioepis, Ariad Pharmaceuticals, Baxalta GMBH/Servier Affaires, Bayer healthcare, Guardanth health, Piqur Therapeutics, Puma C, and Queen Mary University of London. PR serves as consultant for MaxiVax, Enterome, and Inotrem. EAM is on the SAB for AstraZeneca/Medimmune, Celgene, Genentech, Genomic Health, Merck, Peregrine Pharmaceuticals, SELLAS Lifescience, and Tapimmune and has clinical trial support to her former institution (MDACC) from AstraZeneca/Medimmune, EMD-Serono, Galena Biopharma, and Genentech as well as Genentech support to a SU2C grant, as well as sponsored research support to the laboratory from GSK and Eli Lilly. MLD has stock ownership of VentiRX and Epithany. MLD has received grant funding from EMD Serono, VentiRx, Seattle Genetics, and Celgene. GC served as consultant or advisor for Roche, Lilly, and Bristol-Myers Squibb; served on the speaker's bureau for Roche, Pfizer, and Lilly; received travel funding from Pfizer and Roche; and received honoraria from Roche, Pfizer, Lilly, Novartis, and SEAGEN, all outside the submitted work. EAM has been compensated for participation on SABs for Exact Sciences, Merch and Roche, and uncompensated participation on steering committees for BMS, Lilly, and Roche. The remaining authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Introduction: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies., Aims: This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers., Materials and Methods: The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive 99m Tc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module., Results: Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (Β = -0.55; P < 0.0001), global longitudinal strain (Β =0.35; P < 0.008), and regional relative strain ratio (Β = -0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55-0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: a GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%., Conclusions: The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA., Competing Interests: GL had travel grant from AMICUS and speaker fee from Pfizer., (Copyright: © 2021 Journal of Cardiovascular Echography.)

Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody-drug conjugates (ADCs) are a relatively new class of anticancer drugs. By merging the selectivity of monoclonal antibodies with the cytotoxic properties of chemotherapy, they improve the therapeutic index of antineoplastic agents. Three core components characterize ADCs: the antibody, directed to a target antigen; the payload, typically a cytotoxic agent; a linker, connecting the antibody to the payload. The most studied target antigen is HER2 with some agents, such as trastuzumab deruxtecan, showing activity not only in HER2-positive, but also in HER2-low BC patients, possibly due to a bystander effect. This property to provide a cytotoxic impact also against off-target cancer cells may overcome the intratumoral heterogeneity of some target antigens. Other cancer-associated antigens represent a strategy for the development of ADCs against triple-negative BC, as shown by the recent approval of sacituzumab govitecan. In this review, we discuss the current landscape of ADC development for the treatment of BC, as well as the possible limitations of this treatment.

Polycarbonate (PC) is a good material for covering and protecting cultural heritage sites because of its durability, mechanical properties, and transparency. When bisphenol A polycarbonate is subjected to weathering conditions this polymer shows several degradation processes depending on the irradiation wavelength, humidity and temperature. In particular, the combined effects of humidity and UV irradiation speed up the PC molecular weight reduction. In this work, the decomposition mechanisms associated to the hydrolysis process are scrutinized and the effects of UV irradiation on the hydrolysis process are evaluated throughout the Density Functional Theory (DFT) approach. It was found that under UV irradiation the hydrolysis process is speeded up because of the geometrical rearrangement due to the photo-Fries process induced by the UV light., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polymer films based on biodegradable polymers, polyethylene (PE) and modified PE with oxo-degradable additive were prepared by film blowing. Carbon black (1%) was added to all the films. Commercial biodegradable Ecovio ® and Mater-Bi ® samples were used. Mechanical properties, soil burial degradation and surface wettability were investigated, before and after UV irradiation. Chemical modifications induced by UV and soil degradation, or a synergic effect, were highlighted by Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR). Photo-oxidized film samples with an elongation at break equal to 50% and 0.5 the initial value were selected for the soil burial degradation test at 30 °C. Weight loss measurements were used to follow biodegradation in soil. Predictably, the degradation in soil was higher for biodegradable polymer-based films than for the PE-based ones. UV irradiation increased surface wettability and encouraged the disintegration in soil of all the samples. In fact, photo-oxidation produced a molar mass reduction and hydrophilic end groups, thus increasing surface erosion and weight loss. This paper not only supplies new criteria to evaluate the performance of biodegradable films in agriculture, before and after lifetime, but also provides a comparative analysis on the soil burial degradation behaviour with traditional ones., Competing Interests: “The authors declare no conflict of interest.”

Percutaneous mitral valve repair with the MitraClip system recently emerged as a viable and less invasive therapeutic option in patients with severe mitral regurgitation deemed to be high-risk surgical candidates. Mitral valve morphology and geometry features are key elements for MitraClip eligibility. In the setting of functional mitral regurgitation, the presence of a leaflet coaptation gap due to advanced left ventricle remodeling can be a potential exclusion criterion for MitraClip therapy. In this article, the authors present a case of successful MitraClip implantation in a patient with severe functional mitral regurgitation and a significant coaptation gap. Periprocedural and intraoperative pharmacological and anesthesiological management were fundamental for successful grasping and procedural success.

Polycarbonate is a good material for covering and protecting cultural heritage sites because of its durability, mechanical properties, and transparency. However, polycarbonate degrades under environmental weathering with a significant decrease of physical and mechanical properties and loss of transparency. In this work, the contemporary presence of ultraviolet irradiation and different temperature and moisture conditions have been taken into account to study the environmental degradation of this polymer with regard to its mechanical and optical properties. The photo-oxidation reactions cause a decrease in the molecular weight and the formation of many oxygenated species. The hydrolytic scission, instead, gives rise to a remarkable reduction in the molecular weight. These two different degradation mechanisms do not seem interconnected because at the lowest degradation temperature and high humidity levels, the reduction of the molecular weight is more pronounced than that observed at the highest temperature but at a lower humidity level. Transparency decreases with the degradative processes, but even after severe degradation the loss of transparency is only about 10%. The yellowness index increases during the first stages of degradation, which has been attributed to the fast formation of carbonyl groups due to photo-oxidation.

Infective endocarditis (IE) is a rare disease with a significant impact and an increasing mortality despite earlier diagnosis and surgical intervention. It is related to several and the main etiological agents are the Gram-positive cocci. The new guidelines propose new diagnostic criteria that consider the potentiality on integrated multimodality imaging. Echocardiography (TTE) plays a key role for the diagnosis of IE and must be performed as soon as IE is suspected. It allows to identify vegetation, abscess, new dehiscence of prosthetic valve and assesses the number, size, shape, location, echogenicity and mobility of vegetations so it also useful for prediction embolic risk. Transesophageal echocardiography (TEE) is indicated when TTE is positive or non diagnostic, in case of suspected complications and when intracardiac device leads are present. We underline the increasing role of three-dimensional (3D) echocardiography in overcoming the limit of 2DTEE in selecting the maximum true diameter of irregular masses (ie, vegetation). We also underline the diagnostic value of multislice computed tomograpfy (MSCT), cerebral magnetic resonance (RMI) and nuclear imaging and also emphasize the emerging role of particular types of endocarditis specially Lead Endocarditis. The aim of this review is to provide an overview of the imaging techniques useful for the diagnosis and identification of any complications. In our opinion, the management of IE is complex, based on an "Endocarditis team " composed by several specialist and an integrated multimodality imaging is essential for the diagnostic approach., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Cardiovascular Echography.)

Aims: Functional mitral regurgitation (FMR) is a well-known pathophysiological factor in heart failure (HF) patients, and left atrial function (LAF) is a novel determinant of clinical status and outcome in this setting. However, little is known about the pathophysiological role of FMR on LAF in HFrEF patients. Aim of this study is to explore the possible interplay between the severity of FMR and LAF in heart failure with reduce ejection fraction (HFrEF) patients and their possible consequences., Methods and Results: We studied 97 consecutive patients with FMR classified in two groups: mild-to-moderate MR ore less (FMR group, n = 38) and moderate-to-severe or more (SFMR group, n = 59). Using the phasic method, left atrial contractile, conduit, reservoir, and total emptying function (TLAEF) were calculated to assess LAF. SFMR group showed significantly lower values of LAF compared to FMR group. LA dysfunction (LA-dys) was defined for TLAEF values below the median and groups divided in four subgroups based on its presence. Patient with LA-Dys in SFMR group showed a worse clinical status, higher incidence of right ventricular dysfunction (RV-Dys), and pulmonary hypertension (PH), and a significant worse clinical survival compared to all other groups., Conclusion: In our study, the survival was significantly lower in SFMR/LA-Dys+ group. Furthermore, LA-Dys was strongly related with worse clinical status and higher incidence of PH and RV-Dys. These results suggest that in patients with SFMR and HFrEF, LA-Dys may represent both a marker of more advanced disease and a novel prognostic factor., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Atrial fibrillation is the most common cardiac arrhythmia and is associated with an increased risk of stroke and thromboembolic complications. A rhythm control strategy with both electrical and pharmacological cardioversion is recommended for patients with symptomatic atrial fibrillation. Anticoagulant therapy for 3-4 weeks prior to cardioversion is recommended in order to avoid thromboembolic events deriving from restoring sinus rhythm. Transesophageal echocardiography has a pivotal role in this setting, excluding the presence of left atrial appendage thrombus before cardioversion. The aim of this review is to discuss the epidemiology and risk factors for left atrial appendage thrombosis, the role of echocardiography in the decision making before cardioversion, and the efficacy of different anticoagulant regimens on the detection and treatment of left atrial appendage thrombosis.

Introduction: Percutaneous mitral valve repair (PMVR) using MitraClip system has emerged as a therapeutic option for patients with functional severe mitral regurgitation (FMR) at prohibitive risk for surgery. In this setting, the echocardiographic assessment of FMR severity is challenging because the traditional echocardiographic methods have important limitations. The aim of this study was to assess the accuracy and reliability of a simple Doppler index, the mitral/aortic flow velocity integral ratio (MAVIR), to evaluate residual FMR severity after PMVR., Methods: Eighty-five heart failure patients with functional MR and LV dysfunction (LVEF ≤ 40%) were included. FMR was quantified on the basis of traditional quantitative parameters of MR severity. MAVIR was expressed as the ratio of mitral and aortic time velocity integral (TVI) values. According to MR severity, 25 patients underwent MC implantation and at 6 months a complete echocardiographic follow-up was performed., Results: A significant linear relationship was found between MAVIR and both VC and EROA. A MAVIR ≥1.02 identified pts with severe MR with a sensitivity of 86.7% and a specificity of 90.9%. At the 6 months echocardiographic follow-up after the MitraClip implantation, we observed a significant reduction of LAVI, LVED and LVES volume, while LVEF improved. Furthermore, MAVIR significantly decreased its decrease showed a significant linear relationship with LAVI reduction., Conclusion: Our data show a close relationship between MAVIR and traditional indexes of MR severity in patients with FMR. This Doppler-derived index seems applicable after PMVR where traditional echocardiographic index of MR severity shows significant limitations., (© 2017, Wiley Periodicals, Inc.)

The rising concerns in terms of environmental protection and the search for more versatile polymer-based materials have led to an increasing interest in the use of polymer composites filled with natural organic fillers (biodegradable and/or coming from renewable resources) as a replacement for traditional mineral inorganic fillers. At the same time, the recycling of polymers is still of fundamental importance in order to optimize the utilization of available resources, reducing the environmental impact related to the life cycle of polymer-based items. Green composites from biopolymer matrix and wood flour were prepared and the investigation focused on several issues, such as the effect of reprocessing on the matrix properties, wood flour loading effects on virgin and reprocessed biopolymer, and wood flour effects on material reprocessability. Tensile, Dynamic-mechanical thermal (DMTA), differential scanning calorimetry (DSC) and creep tests were performed, pointing out that wood flour leads to an improvement of rigidity and creep resistance in comparison to the pristine polymer, without compromising other properties such as the tensile strength. The biopolymer also showed a good resistance to multiple reprocessing; the latter even allowed for improving some properties of the obtained green composites.

Background and Aims: Intraventricular dyssynchrony has traditionally been studied by means of contraction delays between different myocardial segments. Recently, the discoordination of opposing wall contraction throughout the cardiac cycle has been proposed as a more faithful predictor of response. Aim of the current study was to evaluate which parameters - mechanical dyssynchrony or discoordination - normalize with left ventricular response to cardiac resynchronization therapy (CRT)., Methods: Cardiac mechanics were analysed before and after 6 months of CRT in 53 patients with left bundle branch block and advanced heart failure. Discoordination was quantified by means of the transverse strain discoordination index (TSDI) at basal and mid-ventricular segments; this index takes into account the percentage of time in the cardiac cycle in which cardiac deformation (transverse strain) of the two opposing walls occurs in noncoordinated directions. Dyssynchrony indices included septal to lateral peak-to-peak transverse strain delay and the standard deviation of time to peak tissue velocity in 12 mid-basal segments (Yu index)., Results: Around 63% of patients met the response criteria. Several baseline indices were predictive of reverse remodelling; TSDI at the mid-ventricular level demonstrated the best accuracy. Time from Q to peak velocity and strain tended to increase in all explored myocardial segments; despite a trend towards a decrease in septal-to-lateral strain delay, the latter decreased equally in responders and in nonresponding patients. Yu index decreased in responders more than in nonresponders, with borderline significance. Basal and medium TSDI remained unchanged in nonresponders and consistently normalized in patients who responded to CRT. The changes in TSDI were significantly correlated with improvements in left ventricular end-systolic volume and ejection fraction; the strongest correlation was observed for changes in TSDI measured at the mid-ventricular level., Conclusion: Left ventricular reverse remodelling after CRT is accompanied by the recoordination of opposite-wall contraction, as testified by changes in mid-ventricular TSDI, which also reveals as a very good predictor of response. On the contrary, changes of segmental peak-to-peak delays (dyssynchrony indices) fail to capture the complex nature of left ventricular response to CRT.

Patients submitted to valve replacement with mechanical or biological prosthesis, may present symptoms related either to valvular malfunction or ventricular dysfunction from other causes. Because a clinical examination is not sufficient to evaluate a prosthetic valve, several diagnostic methods have been proposed to assess the functional status of a prosthetic valve. This review provides an overview of echocardiographic and Doppler techniques useful in evaluation of prosthetic heart valves. Compared to native valves, echocardiographic evaluation of prosthetic valves is certainly more complex, both for the examination and the interpretation. Echocardiography also allows discriminating between intra- and/or peri-prosthetic regurgitation, present in the majority of mechanical valves. Transthoracic echocardiography (TTE) requires different angles of the probe with unconventional views. Transesophageal echocardiography (TEE) is the method of choice in presence of technical difficulties. Three-dimensional (3D)-TEE seems to be superior to 2D-TEE, especially in the assessment of paravalvular leak regurgitation (PVL) that it provides improved localization and analysis of the PVL size and shape., Competing Interests: Conflict of Interest: None declared.

Aims: Coronary flow reserve (CFR) assessment by transthoracic ultrasound of the left anterior descending (LAD) artery during dipyridamole stress echocardiography has been shown to predict prognosis in large unselected populations. Low values of CFR are strongly correlated with significant stenosis of the LAD; aim of the present study was to assess the prognostic impact of CFR in patients recovering from an acute coronary syndrome (ACS) with proven absence of LAD disease., Methods: From an overall cohort of 325 patients with ACS who underwent a high-dose dipyridamole stress with combined assessment of CFR in the LAD and wall motion, 152 patients without LAD disease (stenosis <50%) were included in the present analysis; all subjects underwent coronary angiography and were subsequently monitored for the incidence of major cardiac events (MACE)., Results: After a median follow-up of 29 months, 22 patients developed MACE. Patients who experienced MACE differed from stable patients in terms of age, prevalence of diabetes, and CFR. Receiver-operating characteristic curve analysis defined a CFR <2.25 as the optimal cut point for prediction of MACE. Cox multivariable analysis for the prediction of MACE demonstrated independent predictive value only for CFR <2.25, smoking status, and number of stenotic vessels at angiogram., Conclusion: In high-risk patients with ACS, even in the absence of LAD disease, CFR significantly improves prediction of adverse events when added to standard evaluation. This finding supports a role of CFR in the risk stratification early after ACS and is in context with the concept that CFR reflects global atherosclerotic burden, endothelial dysfunction, and microvascular damage, more than just mirroring focal LAD disease.

The key structural factors underlying the unique black chromophore of eumelanin biopolymers have so far defied elucidation. Capitalizing on the ability of 1% polyvinylalcohol (PVA) to prevent pigment precipitation during melanogenesis in vitro, we have investigated the visible chromophore properties of soluble eumelanin-like polymers produced by biomimetic oxidation of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in 1% PVA-containing buffer at pH 7. Upon dilution DHI-eumelanin solutions exhibited almost linear visible absorbance changes, whereas DHICA-eumelanin displayed a remarkable deviation from linearity in simple buffer, but not in PVA-containing buffer. It is suggested that in DHICA polymers, exhibiting repeated interruptions of interring conjugation due to lack of planar conformations, the black chromophore is not due to an overlap of static entities defined intrinsically by the conjugation length across the carbon frame, but results largely from aggregation-related intermolecular perturbations of the π-electron systems which are extrinsic in character., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

Two hundred and 91 patients showing signs and symptoms of bacterial vaginosis (BV) were randomized to receive topical treatment with Fitostimoline (vaginal cream and vaginal ovules + vaginal washing) or benzydamine hydrochloride (vaginal cream + vaginal washing) for 7 days. Signs (leucorrhoea, erythema, oedema, and erosion) and symptoms (burning, pain, itching, vaginal dryness, dyspareunia, and dysuria) (scored 0-3) were evaluated at baseline and at the end of treatment; the total symptoms score (TSS) was also calculated. In 125 patients, a bacterial vaginosis was confirmed by vaginal swab test. The primary efficacy variable analysis, that is, the percentage of patients with therapeutic success (almost complete disappearance of signs and symptoms), demonstrated that Fitostimoline ovules and vaginal cream were therapeutically equivalent and that pooled Fitostimoline treatment was not inferior to benzydamine hydrochloride. All the treatments were well tolerated, with only minor local adverse events infrequently reported. The results of this study confirmed that gynaecological Fitostimoline is a safe and effective topical treatment for BV.

We assessed the clinical characteristics and determinants of the prognosis of patients with left ventricular ballooning syndrome (LVBS) in an European population. A total of 128 patients with LVBS (98% women, age 67 ± 11 years) were prospectively followed up for a median of 13 months. A trigger event was identifiable in 58% of the patients. Anterior ST-segment elevation was documented in 38% and negative T waves in 41% of the patients. Apical ballooning was present in 82% and midventricular ballooning in 18%. The initial LV ejection fraction was 41 ± 9%. In-hospital events included the death of 1 patient (0.8%), LV failure in 13 (10%), LV thrombi in 4 (3.1%), sustained ventricular or supraventricular tachyarrhythmias in 6 (4.7%) and asystole in 2 patients (1.6%). The extent of wall motion abnormalities (odds ratio 4.16, p = 0.012), dyspnea at presentation (odds ratio 3.42, p = 0.01), and treatment with nitrates (odds ratio 0.30, p = 0.015) were significant univariate predictors of in-hospital events. The recovery of regional wall motion abnormalities occurred within 1 month of the event in 73% of patients. During follow-up, events occurred in 7 (6%) of 121 patients, including noncardiac death in 1 (0.8%), recurrent LVBS in 2 (1.6%), heart failure in 1 (0.8%), and recurrent chest pain in 3 (2.5%). In conclusion, in a European population, LVBS was characterized by a significant rate of in-hospital events, mainly related to pump failure, and low short-term mortality. The extent of wall motion abnormalities was the best predictor of acute events. Contractile recovery occurred within 1 month in most patients. The long-term prognosis was good, with a recurrence rate of <2%/year., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In patients with idiopathic dilated cardiomyopathy (DCM) a more depressed left atrial (LA) booster pump function has been observed compared to ischemic patients although under similar loading conditions, and attributed both to altered LA overload and to LA larger involvement in the myopathic process., Aim of the Study: To detect by speckle-tracking two-dimensional strain (2DSE) LA systolic dysfunction in patients with either idiopathic or ischemic DCM, and to assess in these patients possible correlation between LA myocardial function and exercise capacity during cardiopulmonary test., Methods: Three-hundred-fourteen patients (52.4+/-11.2 years) with either idiopathic (160 patients) or ischemic (154 patients) DCM underwent cardiopulmonary stress test, standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof., Results: The two groups were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. Also LA diameter and maximal volume were similar between the two groups. Conversely, LA active empting volume and fraction were both lower in patients with idiopathic DCM (<0.001). Peak systolic myocardial atrial strain was significantly reduced in patients with idiopathic DCM compared with ischemic DCM at the level of all the analyzed atrial segments (p<0.0001). By multivariable analysis, in the overall population, ischemic aetiology of DCM (p<0.0001) and LA volume (p<0.001) were the only independent determinants of LA lateral wall systolic strain. On the other hand, LA lateral wall systolic strain (p<0.0001) and LA volume (p<0.001) were powerful independent predictors of peak oxygen consumption during cardiopulmonary exercise testing., Conclusions: Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA systolic deformation is more depressed in idiopathic compared with ischemic DCM, and is closely associated with functional capacity during effort. Future longitudinal studies are warranted to further our understanding of the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with therapy, and the possible prognostic impact of such indexes in patients with congestive heart failure.

Background: Much information is available regarding the possible negative effects of long-term right ventricular (RV) apical pacing, which may cause worsening of heart failure. However, very limited data are available regarding the effects of RV pacing in patients with a previous myocardial infarction (MI)., Methods and Results: We screened 115 consecutive post-MI patients and matched a group of 29 pacemaker (PM) recipients with a group of 49 unpaced patients, for age, left ventricular (LV) ejection fraction, and site of MI. During a median follow-up of 54 months, echocardiograms showed a decrease in LV ejection fraction in the paced group, from 51 +/- 10 to 39 +/- 11 (P < 0.01), and a minimal change in the unpaced group, from 57 +/- 8 to 56 +/- 7 (P = 0.98). Similar change was observed in systolic and diastolic diameters and volumes., Conclusions: The study showed that, in post-MI patients, RV apical pacing was associated with a worsening of LV function, suggesting that, among MI survivors, the need for a PM is a marker of worse outcome.

Aims: To evaluate whether quantification of the extent of scarred left ventricular (LV) tissue by speckle-tracking strain echo (2DSE) can predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic dilated cardiomyopathy (DCM)., Methods and Results: Forty-five patients (58.3 +/- 8.3 years; 24 males) with ischaemic DCM scheduled for CRT, and 25 controls were studied. A week before implantation all the patients underwent standard Doppler echo, 2DSE, and contrast-enhanced magnetic resonance (MR). Clinical and echocardiographic evaluation was repeated 6 months after CRT. The patients were considered as responders to CRT if LV end-systolic volume decreased by 15%. In DCM patients, LV ejection fraction was 29.2 +/- 5.1%. By evaluating the 765 segments with MR, subendocardial infarct was identified in 17.0% and transmural infarct in 18.3%. With 2DSE, the average global longitudinal strain (GLS) was -23.1 +/- 3.6% in controls and -15.1 +/- 5.1% in DCM (P = 0.001). GLS showed a close correlation with total scar burden using MR (r = 0.64, P < 0.001). At follow-up, patients were subdivided into responders (n = 30; 66.7%) and non-responders (n = 15; 33.3%) to CRT. GLS was significantly different in non-responders than in responders (GLS: -10.4 +/- 5.1 in non-responders vs. -18.4 +/- 14% in responders, P < 0.001). In a multivariable analysis, GLS (P < 0.0001) and radial intraventricular dyssynchrony (P < 0.001) were powerful independent determinants of response to CRT., Conclusion: GLS is strongly associated with total scar burden assessed by MR, and is an excellent independent predictor of response to CRT.

Introduction: We evaluated whether the dobutamine stress-echo test can select responders to cardiac resynchronization therapy (CRT). Up to 50% of patients do not respond to CRT. Lack of response may be due to a significant amount of scar or fibrotic tissue at myocardial level., Methods and Results: We studied 42 CRT patients. After clinical and echocardiographic evaluation, all patients underwent a dobutamine stress-echo test to assess contractile reserve. Cut-off for the test was an increase of 25% of the left ventricular ejection fraction. Patients were implanted with a CRT-defibrillator and followed up at 6 months. Cut-off for CRT response was a reduction of 15% of left ventricular end-systolic volume. Twenty-five patients responded to CRT; all of them showed presence of contractile reserve. The test showed a sensitivity of 100% and a specificity of 88%., Conclusion: Contractile reserve was a strong predictive factor of response to CRT in the studied population.

Background: The aim of this study was to evaluate whether in patients with ischemic heart failure (HF) with mechanical dyssynchrony the echocardiographic assessment of the extent of scarred ventricular tissue by end-diastolic wall thickness (EDWT) could predict reverse remodeling (RR) after cardiac resynchronization therapy (CRT). Recent studies using cardiac magnetic resonance imaging have shown that the burden of myocardial scar is an important factor influencing response to CRT, despite documented mechanical dyssynchrony. EDWT assessed by two-dimensional (2D) resting echocardiography is a simple and reliable marker to identify scar tissue in patients with ischemic left ventricular dysfunction., Methods: Seventy-four patients with ischemic HF were evaluated 1 week before and 6 months after CRT. Inclusion criteria were New York Heart Association class III or IV, ejection fraction < 35%, QRS duration > 120 ms, and mechanical intraventricular dyssynchrony >/= 65 ms. The left ventricle was divided into 16 segments; left ventricular (LV) segments with EDWT < 6 mm were considered scarred. Percentage global scar area (GSA) was calculated by dividing the number of scarred LV segments by 16., Results: RR, defined as a reduction of LV end-systolic volume >/= 15%, was found in 38 patients (51.4%) with ischemic HF. A significant inverse linear relationship was found between GSA and RR (r = -0.57; P = .0001). Mean percentage GSA was significantly higher in nonresponders (31.6 +/- 18% vs 6.4 +/- 11%; P < .001). GSA

Background: Cardiac mechanical efficiency requires that opposing left ventricular regions are coupled both in shortening and lengthening during the same phase of cardiac cycle. Aim of this study was to evaluate whether global measures of mechanical dyssynchrony are able to predict reverse remodeling of the left ventricle in patients receiving cardiac resynchronization therapy (CRT)., Methods: Sixty-two patients underwent a clinical examination, including New York Heart Association class evaluation and 6-minute walking distance and both echocardiographic study before and 6 months after CRT. Intraventricular dyssynchrony was evaluated by two-dimensional strain echocardiography, measuring the amount of uncoordinated contraction and relaxation between septum and free wall for both longitudinal and radial function and was presented as the longitudinal global dyssynchrony index (LGDI) and the radial global dyssynchrony index (RGDI). Reverse remodeling was defined by a left ventricular end systolic volume reduction >or= 15%., Results: After CRT 39 patients showed reverse remodeling. In this group, RGDI (0.74 +/- 0.26 vs 0.32 +/- 0.30; P = 0.0001) and LGDI (0.52 +/- 0.28 vs 0.30 +/- 0.24; P = 0.002) were significantly higher than in nonresponders. A receiver-operating characteristic curve analysis showed that RGDI >0.47 and LGDI >0.34 had a sensitivity and a specificity to predict reverse remodeling of 87% and 74%, 82%, and 74%, respectively. Stepwise forward multiple logistic regression analysis showed that RGDI (O.R.:13.4; 95%C.I.:4.2-120.5; P < 0.0001) was an independent determinant of a positive response to CRT., Conclusion: A radial global dyssynchrony index predicts left ventricular reverse remodeling after CRT.

Objective: To evaluate the impact of multiple cardiovascular risk factors on coronary flow reserve (CFR) in a large patient population with acute chest pain referred for coronary angiography., Methods: Three hundred and ninety-four consecutive patients (mean age 59 +/- 10 years) were enrolled in the study. Blood flow velocity was measured, using transthoracic echocardiography, in the middle-distal tract of the left anterior descending coronary artery (LAD) at rest and during infusion of high-dose dipyridamole in 6 min. CFR was calculated as the ratio of hyperaemic to basal peak diastolic flow velocity. All patients underwent coronary angiography within 48-72 h of CFR evaluation and a LAD stenosis was considered significant for lumen diameter narrowing > or =70%., Results: Out of 394 patients, 11 patients (3%) were excluded because of inadequate quality of the spectral Doppler envelope. In the group of 269 patients with LAD stenosis <70%, CFR was significantly reduced in 64 patients with >2 risk factors compared to 205 patients with < or =2 risk factors (2.24 +/- 0.48 vs. 2.52 +/- 0.53, P < 0.005). On multiple logistic regression analysis, age, hypertension and diabetes mellitus were related to reduced CFR. In 114 patients with significant LAD disease, CFR was not reduced in patients with multiple cardiovascular risk factors. On multiple logistic regression analysis, the percentages of stenosis and diabetes mellitus were independent determinants of CFR., Conclusions: In patients with acute chest pain, the occurrence of multiple cardiovascular risk factors adversely affected CFR in an additive manner, in absence of significant angiographic stenosis. Diabetes mellitus was a powerful coronary risk factor decreasing CFR both in patients with or without significant LAD disease.

We report a case of tako-tsubo cardiomyopathy, complicated by left ventricular apical thrombus.

Introduction: Permanent right ventricular (RV) pacing leads have been traditionally implanted in the right ventricular apex (RVA). Nowadays, some deleterious effects of RVA pacing have been recognized. The aim of this study was to evaluate the effect of different sites of RV pacing in patients with permanent atrial fibrillation (AF) and low ejection fraction (LEF) needing a pacemaker (PM) implantation., Methods: Two hundred seventy-three patients with permanent AF and EF <30% underwent a one-chamber rate responsive (VVIR) PM implant procedure. Patients were divided into two groups: Group A, including 113 patients with the pacing lead tip placed in the RV mid-septum, and Group B of 120 patients with the pacing lead tip placed at the apex of RV. All patients had clinical and Echo control after 1, 3, 6, 12, and 18 months after PM implantation to assess New York Heart Association (NYHA) class and EF., Results: After 18 months, NYHA class changed in Group A from 2.9 +/- 0.4 at implant to 1.7 +/- 0.3 at 18 months (P = 0.01), and in Group B from 3.0 +/- 0.5 at implant to 3.3 +/- 0.6 at 18 months (P = n.s.). EF increased in Group A: 28 +/- 2% at implant, 33 +/- 1% at 18 months (P = 0.0125), while no significant changes were observed in Group B: at implant 27 +/- 2%, 26 +/- 2% at 18 months (P = n.s.)., Conclusion: The present study suggests that more physiological pacing from the RV sept can improve EF and quality of life (QoL) in patients with permanent AF and low EF needing a PM.

Objective: The aim of this prospective, randomised study was to evaluate the efficacy, safety and long-term outcomes of the complete disappearance of local electrograms along the linear lesion using the EnSite NavX three-dimensional mapping system as compared with conventional fluoroscopy for ablation of typical atrial flutter (AFL)., Methods: Seventy-three patients with spontaneous AFL episodes were randomised to undergo fluoroscopy-guided (group I, n=35) or EnSite NavX-guided (group II, n=38) ablation. When bidirectional isthmus block was achieved, the catheter was navigated back along the ablation line to assess the presence of local potentials along the lesion line., Results: Bidirectional isthmus block was achieved in all patients. Mean total fluoroscopy time was 19.8 +/- 4.1 min in group I and 9.1 +/- 3.5 min in group II (P<0.001); mean fluoroscopy time required for radiofrequency ablation was 6.9 +/- 1.4 min in group I and 0.6 +/- 0.3 min in group II (P<0.001). During a follow-up of 16 +/- 9 months, three patients in group I (10%) experienced recurrence of AFL as opposed to none in group II (P<0.005)., Conclusions: NavX technology allows accurate re-navigation of the lesion line to assess the presence of local potentials during an ablation procedure for typical AFL. Electroanatomic activation mapping can accurately identify gaps in the linear radiofrequency lesion with no AFL recurrence compared with 20% of recurrences after a standard procedure.

Aims: Cardiac resynchronization therapy (CRT) has become an attractive therapeutic option for patients with end-stage heart failure (HF). Currently, patients are selected for CRT on ECG and on echocardiographic criteria analysed at rest. Whether the physical effort may further increase myocardial dyssynchrony is not fully established. The aim of the study was to test by the use of Doppler myocardial imaging (DMI) if dynamic left ventricular (LV) dyssynchrony during physical effort may be a determinant of dynamic mitral regurgitation in patients with dilated cardiomyopathy and 'narrow' QRS., Methods and Results: Sixty patients (62.3 +/- 8.3 years) with idiopathic dilated cardiomyopathy and narrow QRS duration ( < 120 ms) were selected. All the patients underwent standard Doppler echo, colour DMI, supine bicycle exercise stress echocardiography, and cardiopulmonary exercise testing. Cardiac synchronicity was assessed, at rest and at peak exercise, from measurements of time intervals (Ts) between the onset of the QRS complex and the peak myocardial systolic velocity, in a six-basal-six-mid-segmental model. Standard deviation of Ts of the 12 LV segments (Ts-SD-12) was also calculated. In baseline conditions, HF patients showed an LV ejection fraction of 30.1 +/- 4%, and a significant electromechanical delay (Ts-SD-12 > or = 34.4 ms) in 20 patients (33.3%). At peak of physical exercise, a significant electromechanical delay was detected in 35 patients (58.3%), whereas in 47 patients (78.3%) exercise-induced increase in mitral valve effective regurgitant orifice (ERO) was observed. By multivariable analysis, an independent positive association between changes in Ts-SD-12 and in mitral valve ERO (P < 0.0001), as well as an independent inverse correlation of the same changes in Ts-SD-12 with LV stroke volume (P < 0.0001) were detected. In addition, changes in Ts-SD-12 were also independent determinants of peak VO(2) (P < 0.0001) during cardiopulmonary exercise testing., Conclusion: Colour DMI is an effective technique for assessing the severity of regional delay in activation of LV walls in HF patients with narrow QRS both at rest and during stress test. The increase in LV dyssynchrony during exercise strongly correlates with the increase in mitral regurgitation severity and with the impairment of LV stroke volume.

Background: Conflicting data have been reported about the nature (physiologic versus pathologic) of left ventricular (LV) hypertrophy in master athletes., Aim of the Study: To analyze LV and right ventricular (RV) myocardial function in master athletes with LV hypertrophy induced by either endurance or strength training., Methods: Standard Doppler echo and colour Doppler Myocardial Imaging (DMI) of LV and of RV basal lateral walls were performed in 40 competitive master (>45 years) endurance athletes (ATE), in 20 master strength-trained athletes (ATS) and 25 age-matched healthy sedentary subjects, all males. By use of DMI, the following parameters of myocardial function were assessed: systolic peak velocities, precontraction time, contraction time, early (E(m)) and late (A(m)) diastolic peak velocities, E(m)/A(m) ratio, relaxation time., Results: The two groups were comparable for age, but ATS at rest showed higher heart rate, systolic blood pressure, and body surface area. LV mass index did not significantly differ between the two groups of athletes. However, ATS showed increased wall thickness and relative wall thickness, while LV stroke volume and both LV and RV end-diastolic diameters were greater in ATE. All transmitral and transtricuspid Doppler indexes were higher in ATE. DMI analysis showed in ATE higher E(m) and E(m)/A(m) ratio at the level of both RV and LV lateral walls. In the overall population of athletes, linear regression models evidenced independent positive association of RV peak E(m) velocity with both LV stroke volume and maximal workload achieved by bicycle ergometer (both p<0.001)., Conclusions: RV early diastolic myocardial function is positively influenced by preload increase in master athletes and represents an independent determinant of cardiac performance during physical effort. Therefore, colour DMI may be taken into account to distinguish different cardiac adaptation to either endurance or strength sport training in master athletes.

A 60-year-old woman with severe chest pain and ECG diagnostic for acute transmural ischemia was transferred to cath lab for primary PTCA. After procedure, transesophageal echocardiography (TEE) views revealed an intramural haematoma extending from the ostium of the RCA throughout the sino-tubular junction. These findings and the stable clinical conditions of patient guided us to a conservative therapeutic approach. A TEE study, performed 5 days after admission, showed a complete resolution of intramural haematoma. A waiting strategy can be a valid therapeutic option in selected patients with iatrogenic haematoma and TEE is a useful diagnostic tool for clinical decision making.

Objective: Coronary blood flow exhibits a biphasic pattern at rest with a higher diastolic and a smaller systolic component. In the present investigation, we evaluated whether a decreased diastolic to systolic velocity ratio of basal coronary flow may be useful in the identification of subjects with significant left anterior descending coronary artery (LAD) stenosis., Methods: One hundred and twenty-nine consecutive patients (62 with unstable angina, 25 with acute myocardial infarction and 42 with chronic coronary artery disease) were included in the study. Blood flow velocities were recorded in the mid-distal portion of the LAD using an ATL 5000 CV HDI ultrasound system. All patients underwent coronary angiography and were divided into two groups according to the absence (group 1) or the presence (group 2) of significant LAD stenosis (lumen narrowing > or = 70%). In 60 of the 129 patients, coronary flow reserve was evaluated non-invasively., Results: Adequate Doppler recordings in the LAD were obtained by transthoracic echocardiography in 113 patients. There were no differences between groups with regard to sex, cardiovascular risk factors, left ventricular mass and volumes, ejection fraction, whereas the diastolic to systolic velocity ratio of basal coronary flow was significantly lower in group 2 patients (1.41 +/- 4.7 vs. 2.08 +/- 0.64, P < 0.00001). The receiver operating characteristic curve showed that a diastolic to systolic velocity ratio < 1.6 had a sensitivity of 77%, a specificity of 91%, a positive predictive value of 77%, a negative predictive value of 97%, and a diagnostic accuracy of 84% for the presence of significant LAD stenosis. In 55/60 patients, results of basal coronary flow and coronary flow reserve were concordant. On multivariate logistic regression analysis, the diastolic to systolic velocity ratio was a strong independent predictor of LAD stenosis > or = 70% (odds ratio 4.90, 95% confidence interval 1.65-7.30)., Conclusions: The present findings suggest that assessment of basal coronary flow in the LAD may be useful to rule out the presence of significant stenosis.

Aims: We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM). The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function., Methods and Results: The study population included 123 HCM patients (39.4+/-5.9 years) and 123 age- and sex-matched healthy subjects, followed up for 48.4+/-8.8 months. By use of pulsed DMI, the following regional parameters were evaluated in six different basal myocardial segments: myocardial peak velocities and systolic time-intervals; myocardial intraventricular (intra-V-Del) and interventricular (inter-V-Del) systolic delays. DMI analysis in HCM showed lower myocardial systolic and early-diastolic peak velocities of all the segments. As for time intervals, HCM showed significant inter- and intra-V delays (P<0.0001), whereas homogeneous systolic activation of the ventricular walls was assessed in controls. During the follow-up, 16 cardiac deaths (12 sudden deaths) were observed in HCM patients. InHCM, DMI intra-V-Del was the most powerful independent predictor of sudden cardiac death (P<0.0001). In particular, an intra-V-Del>45 ms is identified with high sensitivity and specificity in HCM patients at higher risk of ventricular tachycardia and sudden cardiac death (test accuracy: 88.8%)., Conclusion: In HCM patients, DMI indexes of intra-V-Del may provide additional information for selecting subgroups of HCM patients at increased risk of ventricular arrhythmias and sudden cardiac death at follow-up. Accordingly, such patients may be more actively identified for early intensive treatment and survey.

Background: Coronary flow reserve (CFR) assessment by transthoracic Doppler echocardiography has been found to be useful in subjects with suspected coronary artery disease. An important clinical question is whether such technique can be successfully applied in patients admitted to the coronary care unit with an acute coronary syndrome to detect a significant left anterior descending (LAD) disease., Methods: One hundred fifty-nine patients with acute coronary syndrome (93 patients with unstable angina, 66 with acute inferior or lateral myocardial infarction) were included in the present analysis. Patients underwent a high-dose dipyridamole stress (0.84 mg/kg) with combined assessment of CFR in the LAD and regional wall motion. Blood flow velocities were recorded in the mid-distal portion of the LAD using a digital ultrasonographic system and CFR was calculated as the ratio of hyperemia-induced peak diastolic velocity to resting peak diastolic flow velocity. All patients underwent coronary angiography and a significant LAD stenosis was classified for lumen narrowing > or = 70%., Results: Adequate Doppler recordings in the LAD were obtained in 92% of patients. A contrast agent was used in the 39% of examinations. No major adverse reaction occurred in any patient. A receiving operating characteristic curve showed that a CFR value < 1.9 had a sensitivity of 85%, a specificity of 87%, a positive predictive value of 71%, a negative predictive value of 94% and a diagnostic accuracy of 86% for identifying a significant LAD stenosis. The area under the receiving operating characteristic curve computed for CFR was significantly higher than for wall motion score index (p < 0.001). In a stepwise forward, multiple logistic regression analysis, both CFR (OR = 4.8, 95% C.I. 3.7-5.3; p < 0.00001) and the wall motion score index for the LAD territory (OR = 4.2, 95% C.I. 2.6-6.8; p < 0.0001) were independent determinants of LAD stenosis > or = 70%., Conclusion: Early assessment of CFR by transthoracic Doppler echocardiography is feasible and safe and provides additional information to identify subjects with acute coronary syndrome and significant LAD stenosis.

Aim of the Study: to evaluate determinants of myocardial activation delay of both left (LV) and right (RV) ventricle in patients with left bundle branch block (LBBB) and either normal or impaired LV ejection fraction (EF)., Methods: From an initial cohort of patients with LBBB, 42 patients with dilated cardiomyopathy (group A) and 33 with normal global LV systolic function (group B), all comparable in age and sex, underwent standard Doppler echo, pulsed Doppler myocardial imaging (DMI), and coronary angiography. Using DMI, the following regional parameters were evaluated in five different basal myocardial segments (LV anterior, inferior, septal, lateral walls-RV lateral wall): systolic (Sm), early- and late-diastolic (Em and Am) peak velocities. As index of myocardial systolic activation was calculated: precontraction time (PCTm) (from the beginning of Q-wave of ECG to the onset of Sm). Intraventricular systolic dyssynchrony was analyzed by difference of PCTm in different LV myocardial segments. Interventricular activation delay was calculated by the difference of PCTm between the most delayed LV segment and RV lateral wall., Results: Patients of group A showed increased heart rate (HR), QRS duration and LV end-diastolic diameter, and reduced LV EF. By DMI, patients of group A showed reduced myocardial peak velocities and a significant intraventricular delay in activation of LV lateral wall, with increased regional PCTm (P < 0.001). In addition, patients with dilated cardiomyopathy showed a more pronounced interventricular dyssynchrony, even after adjustment for HR and QRS duration. By receiver operating characteristic (ROC) curve analysis, a cut-off value of 55 msec of interventricular delay showed 86% sensitivity and 92% specificity in identifying patients with impaired EF. In the overall population, by use of stepwise forward multivariate linear regression analyses, LV end-diastolic diameter (beta coefficient = 0.52; P < 0.001) and LV EF (beta coefficient =-0.58; P < 0.0001) were the only independent determinants of interventricular activation delay., Conclusions: Pulsed DMI is an effective noninvasive technique for assessing the severity of regional delay in activation of LV walls in patients with LBBB. The impairment of interventricular systolic sychronicity is strongly related to LV dilatation and to the degree of global systolic dysfunction. Therefore, patients with dilated cardiomyopathy suitable for cardiac resynchronization therapy may be better selected.

Background: The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with hypertrophic cardiomyopathy (HCM), which results in regional heterogeneity of LV systolic and diastolic function. The aim of the study was to evaluate LV regional systolic asynchrony in patients with HCM by pulsed Doppler myocardial imaging (DMI)., Methods: We studied 35 HCM patients and 45 age- and sex-matched controls. By the use of DMI, the following five different basal myocardial segments were measured: systolic peak velocity (Sm); early- and late-diastolic peak velocities; pre-contraction time (Q-Sm) (from the beginning of Q-wave of ECG to the onset of Sm); intraventricular systolic delay (IntraV-Del) (difference of Q-Sm in different LV myocardial segments); interventricular delay (InterV-Del) (difference of Q-Sm between the most delayed LV segment and right ventricular lateral wall)., Results: DMI analysis showed in HCM lower myocardial systolic and early-diastolic peak velocities of all the analyzed segments. As for time intervals, controls showed homogeneous systolic activation of the ventricular walls. Conversely, HCM group, despite the absence of intraventricular conduction defects by surface ECG, showed significant both Inter- and IntraV-Del (P < 0.0001). Linear regression models pointed out independent positive associations of IntraV-Del with LV outflow gradient and septal wall thickness in HCM (P < 0.001). An IntraV-Del >30 msec well differentiated controls and HCM. In addition, an IntraV-Del > 45 msec (ROC curve) identified a subgroup of HCM patients with nonsustained ventricular tachycardia during Holter monitoring (90.9% sensitivity and 95.8% specificity)., Conclusions: The impairment of intrarventricular systolic synchronicity is strongly related to increased septal thickness and LV outflow-tract gradient in HCM. DMI analysis may be able to select subgroups of HCM patients at an increased risk of ventricular tachyarrhythmias.

Objective: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI)., Design and Setting: Multicentre clinical trial carried out in 47 Italian coronary care units., Patients: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24-48 hours after symptom onset and at discharge, six weeks, and six months after AMI., Results: Tricuspid annular plane systolic excursion (TAPSE) increased significantly during follow up (mean (SD) 1.79 (0.46) cm at 24-48 hours to 1.92 (0.46) cm at six months, p < 0.001) and the increase was already significant at discharge (1.88 (0.47) cm, p < 0.001). LV ejection fraction (LVEF) was the best correlate of TAPSE at 24-48 hours (r = 0.15, p = 0.001). TAPSE increased significantly in patients both with reduced (< 45%) and with preserved (> or = 45%) LVEF, but the magnitude of increase was higher in patients with lower initial LVEF (p = 0.001). Improvement in IVS wall motion score index (IVS-WMSI) was the only independent predictor of TAPSE changes during follow up (r = -0.12, p = 0.007)., Conclusions: In low risk patients after AMI, RV function recovered throughout six months of follow up and was already significant at discharge. TAPSE was significantly related to LVEF at 24-48 hours. The magnitude of RV functional recovery was higher in patients with lower initial LVEF. RV functional recovery is best related to IVS-WMSI improvement, suggesting that IVS motion has an important role in RV functional improvement in this setting.

We briefly describe our experience with transthoracic Doppler echocardiography for the direct evaluation of mid-distal left anterior descending coronary artery (LAD) stenosis. Three patients with previous myocardial infarction, scheduled for coronary flow reserve evaluation, underwent Doppler analysis of the mid-distal LAD. In all 3 cases, the mid-distal LAD stenosis was accurately quantified by the Doppler spectrum as confirmed by quantitative coronary angiography. Our study demonstrated the feasibility of transthoracic Doppler echocardiography in the discrimination of significant and non-significant mid-distal LAD stenosis. Limitations of such a technique could be related to the variable coronary anatomy and to the severity of the atherosclerotic process.

Background: B-mode ultrasound studies indicate that hyperhomocysteinemia is associated with preclinical structural and functional arterial abnormalities. This study was designed to evaluate the effect of elevated plasma homocysteine levels on coronary flow reserve (CFR)., Methods: A total of 20 healthy subjects aged 41 +/- 7 years were studied on 2 separate days, a week apart, before and after methionine load (100 mg/kg of body weight) or placebo in a double-blind crossover study. At each visit, homocysteine levels were measured by high performance liquid chromatography and CFR was determined by transthoracic Doppler echocardiography., Results: After methionine load, plasma homocysteine increased from 10.7 +/- 2.8 mumol/L to 30.4 +/- 5.1 mumol/L ( P < .0001) and CFR decreased from 3.0 +/- 0.4 to 2.3 +/- 0.3 ( P < .001). CFR was inversely related to postload homocysteine levels ( r = -0.21, P = .02). After placebo, there was no change in CFR., Conclusion: In asymptomatic adults, acute hyperhomocysteinemia is associated with a significant reduction in CFR.