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A 71-year-old woman with dilated cardiomyopathy underwent an echocardiogram showing new onset of multiple mobile left ventricular masses. She experienced a mild COVID-19 infection 1 month before. After a multimodality imaging evaluation, vitamin K antagonist treatment was started, with progressive reduction of the masses without clinical events. A diagnosis of exclusion of left ventricular thrombosis was made., Competing Interests: This research was supported by the Italian Ministry of Health–Ricerca Corrente to Centro Cardiologico Monzino IRCCS. Publication fees for this article have been funded by Novartis Farma Italy. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. Cardiac magnetic resonance (CMR) imaging has emerged as a powerful tool for the non-invasive assessment of HCM. CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. We will study basic and advanced features of CMR in 2 groups of HCM patients with negative and positive genotype, respectively., Materials and Methods: The study population consisted in consecutive HCM patients referred to Centro Cardiologico Monzino who performed both CMR and genetic testing. Clinical CMR images were acquired at 1.5 T Discovery MR450 scanner (GE Healthcare, Milwaukee, Wisconsin)) using standardized protocols T1 mapping, T2 mapping and late gadolinium enhancement (LGE). Population was divided in 2 groups: group 1 with HCM patients with a negative genotype and group 2 with a positive genotype., Results: The analytic population consisted of 110 patients: 75 in group 1 and 35 patients in group 2. At CMR evaluation, patients with a positive genotype had higher LV mass (136 vs. 116 g, p = 0.02), LV thickness (17.5 vs. 16.9 mm), right ventricle ejection fraction (63 % vs. 58 %, p = 0.002). Regarding the LGE patients with positive genotype have a higher absolute (33.8 vs 16.7 g, p = 0.0003) and relative LGE mass (31.6 % vs 14.6 %, p = 0.0007). On a segmental analysis all the septum (segments 2, 8, 9, and 14) had a significantly increased native T1 compared to others segments. ECV in the mid antero and infero-septum (segments 8 and 9) have lower values in positive genotype HCM. Interestingly the mean T2 was lower in positive genotype HCM as compared to negative genotype HCM (50,1 ms vs 52,4)., Conclusions: Our paper identifies the mid septum (segments 8 and 9) as a key to diagnose a positive genotype HCM., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy., Methods: We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO 2 )., Results: Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO 2 of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO 2 ) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO 2 slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P < 0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161 ng/L, P < 0.001), peak heart rate (121 ± 28 vs. 115 ± 27 beats/min, P = 0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53 L/min, P < 0.0001) with earlier anaerobic threshold (VO 2 at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7 mL/min/kg, P < 0.0001) compared with HF. Between amyloid patients, AL patients (n = 27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81 years, P < 0.0001), had lower VE/VCO 2 slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P = 0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1 ± 4.8 vs. 31.4 ± 4.7 mmHg, P < 0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33 mmHg, P = 0.039) as compared with ATTR (n = 233)., Conclusions: A higher VE/VCO 2 slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

There are hundreds of genes typically overexpressed in breast cancer cells and it's often assumed that their overexpression contributes to cancer progression. However, the precise proportion of these overexpressed genes contributing to tumorigenicity remains unclear. To address this gap, we undertook a comprehensive screening of a diverse set of seventy-two genes overexpressed in breast cancer. This systematic screening evaluated their potential for inducing malignant transformation and, concurrently, assessed their impact on breast cancer cell proliferation and viability. Select genes including ALDH3B1, CEACAM5, IL8, PYGO2, and WWTR1, exhibited pronounced activity in promoting tumor formation and establishing gene dependencies critical for tumorigenicity. Subsequent investigations revealed that CEACAM5 overexpression triggered the activation of signaling pathways involving β-catenin, Cdk4, and mTOR. Additionally, it conferred a growth advantage independent of exogenous insulin in defined medium and facilitated spheroid expansion by inducing multiple layers of epithelial cells while preserving a hollow lumen. Furthermore, the silencing of CEACAM5 expression synergized with tamoxifen-induced growth inhibition in breast cancer cells. These findings underscore the potential of screening overexpressed genes for both oncogenic drivers and tumor dependencies to expand the repertoire of therapeutic targets for breast cancer treatment., (© 2024. The Author(s).)

Acute aortic syndromes comprise a range of interrelated conditions including aortic dissection, intramural hematoma, penetrating atherosclerotic ulcer, and contained or not contained aortic aneurysm rupture. These syndromes are potentially life threatening; therefore, a rapid and accurate diagnosis is crucial. A new Clinical Consensus Statement on Aortic and Peripheral Vascular Disease has recently been published, and we will try to highlight the main innovations in the document., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Nineteen consecutive patients with apical hypertrophic cardiomyopathy and apical aneurysm underwent a comprehensive echo-Doppler including continuous wave Doppler at midventricular level. Three different flow patterns, pattern A (more frequent), pattern B, and pattern C, and expression of different intracavitary pressure gradients were defined. ( Level of Difficulty: Intermediate. )., Competing Interests: This study was supported by Centro Cardiologico Fondazione Monzino Istituto di Ricovero e Cura a Carattere Scientifico. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction., Methods: A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses., Results: All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively)., Conclusions: Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI., (© 2023. The Author(s).)

Aims: COVID-19 has dramatically impacted the healthcare system. Evidence from previous studies suggests a decline in in-hospital admissions for acute myocardial infarction (AMI) during the pandemic. However, the effect of the pandemic on mechanical complications (MC) in acute ST-segment elevation myocardial infarction (STEMI) has not been comprehensively investigated. Therefore, we evaluated the impact of the pandemic on MC and in-hospital outcomes in STEMI during the second wave, in which there was a huge SARS-CoV-2 diffusion in Italy., Methods and Results: Based on a single center cohort of AMI patients admitted with STEMI between February 1, 2019, and February 28, 2021, we compared the characteristics and outcomes of STEMI patients treated during the pandemic vs. those treated before the pandemic. In total, 479 STEMI patients were included, of which 64.5% were during the pandemic. Relative to before the pandemic, primary percutaneous coronary intervention (PCI) declined (87.7 vs. 94.7%, p = 0.014) during the pandemic. Compared to those admitted before the pandemic (10/2019 to 2/2020), STEMI patients admitted during the second wave (10/2020 to 2/2021) presented with a symptom onset-to-door time greater than 24 h (26.1 vs. 10.3%, p = 0.009) and a reduction of primary PCI (85.2 vs. 97.1%, p = 0.009). MC occurred more often in patients admitted during the second wave of the pandemic than in those admitted before the pandemic (7.0 vs. 0.0%, p = 0.032). In-hospital mortality increased during the second wave (10.6 vs. 2.9%, p = 0.058)., Conclusion: Although the experience gained during the first wave and a more advanced hub-and-spoke system for cardiovascular emergencies persists, late hospitalizations and a high incidence of mechanical complications in STEMI were observed even in the second wave., Competing Interests: The 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., (Copyright © 2022 Penso, Frappampina, Cosentino, Tamborini, Celeste, Ianniruberto, Ravagnani, Troiano, Marenzi and Pepi.)

We aimed to evaluate the feasibility and accuracy of machine learning-based automated dynamic quantification of left ventricular (LV) and left atrial (LA) volumes in an unselected population. We enrolled 600 unselected patients (12% in atrial fibrillation) clinically referred for transthoracic echocardiography (2DTTE), who also underwent 3D echocardiography (3DE) imaging. LV ejection fraction (EF), LV, and LA volumes were obtained from 2D images; 3D images were analyzed using dynamic heart model (DHM) software (Philips) resulting in LV and LA volume-time curves. A subgroup of 140 patients also underwent cardiac magnetic resonance (CMR) imaging. Average time of analysis, feasibility, and image quality were recorded, and results were compared between 2DTTE, DHM, and CMR. The use of DHM was feasible in 522/600 cases (87%). When feasible, the boundary position was considered accurate in 335/522 patients (64%), while major (n = 38) or minor (n = 149) border corrections were needed. The overall time required for DHM datasets was approximately 40 seconds. As expected, DHM LV volumes were larger than 2D ones (end-diastolic volume: 173 ± 64 vs. 142 ± 58 mL, respectively), while no differences were found for LV EF and LA volumes (EF: 55% ± 12 vs. 56% ± 14; LA volume 89 ± 36 vs. 89 ± 38 mL, respectively). The comparison between DHM and CMR values showed a high correlation for LV volumes (r = 0.70 and r = 0.82, p < 0.001 for end-diastolic and end-systolic volume, respectively) and an excellent correlation for EF (r = 0.82, p < 0.001) and LA volumes. The DHM software is feasible, accurate, and quick in a large series of unselected patients, including those with suboptimal 2D images or in atrial fibrillation.

Three-dimensional echocardiographic (3DE) of right ventricle (RV) has been validated in many clinical settings. However, the necessity of complicated and off-line dedicated software has reduced its diffusion. A new simplified "on board" 3DE software (OB) has been developed to obtain RV volumes and ejection fraction (EF) together with several conventional parameters automatically derived from 3DE: tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), longitudinal strain (LS). Aims of this study were to evaluate feasibility and accuracy of OB RV analysis. A complete 2DE and 3DE with OB 3DRV evaluation was obtained in 35 normal subjects and 105 patients with different pathologies. Results were compared with the conventional off-line software (OFL) and with the 2D-derived corresponding values. A subgroup of 22 patients underwent also cardiac CMR. OB 3DRV was feasible in 133/140 cases (95%) in a mean time of 97.5 ± 33 s lower than OFL analysis (129 ± 52 s plus dataset loading 80 ± 24 s). Imaging quality was good in 84%. OB and OFL 3DE RV volumes and EF were similar. 3DE derived FSA and LS (but not TAPSE) were similar to 2DE values and correlated with tissue Doppler systolic peak velocity, dP/dt, systolic pulmonary pressure and myocardial performance index. OB RV volumes and EF well correlated with CMR. (bias + SD: - 21.5 ± 20 mL for EDV; - 8.2 ± 12.4 mL for ESV; - 1 ± 5.9% for EF). OB 3DE method is feasible, simple, time saving. It easily provides 3DE RV volumes and multiple functional parameters. Off-line operator border adjustment may improve accuracy of 3DE TAPSE.

Background: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133 + cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function., Methods: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133 + Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations., Results: Patients were treated safely with a mean number of 6.57 ± 3.45 ×  10 6 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02)., Conclusion: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations., Trial Registration: ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.

GNE myopathy is a rare, autosomal recessive, inborn error of sialic acid metabolism, caused by mutations in GNE, the gene encoding UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase. The disease manifests as an adult-onset myopathy characterized by progressive skeletal muscle weakness and atrophy. There is no medical therapy available for this debilitating disease. Hyposialylation of muscle glycoproteins likely contributes to the pathophysiology of this disease. N-acetyl-D-mannosamine (ManNAc), an uncharged monosaccharide and the first committed precursor in the sialic acid biosynthetic pathway, is a therapeutic candidate that prevents muscle weakness in the mouse model of GNE myopathy. We conducted a first-in-human, randomized, placebo-controlled, double-blind, single-ascending dose study to evaluate safety and pharmacokinetics of ManNAc in GNE myopathy subjects. Single doses of 3 and 6g of oral ManNAc were safe and well tolerated; 10g was associated with diarrhea likely due to unabsorbed ManNAc. Oral ManNAc was absorbed rapidly and exhibited a short half-life (~2.4h). Following administration of a single dose of ManNAc, there was a significant and sustained increase in plasma unconjugated free sialic acid (Neu5Ac) (T max of 8-11h). Neu5Ac levels remained above baseline 48h post-dose in subjects who received a dose of 6 or 10g. Given that Neu5Ac is known to have a short half-life, the prolonged elevation of Neu5Ac after a single dose of ManNAc suggests that intracellular biosynthesis of sialic acid was restored in subjects with GNE myopathy, including those homozygous for mutations in the kinase domain. Simulated plasma concentration-time profiles support a dosing regimen of 6g twice daily for future clinical trials., (Published by Elsevier Inc.)

This report will review the role of echocardiography in the diagnosis of cardiac sources of embolism. Embolism of cardiac origin accounts for around 15%-30% of ischemic strokes. The diagnosis of a cardioembolic source of stroke is frequently uncertain and relies on the identification of a potential cardiac source of embolism in the absence of significant autochthonous cerebrovascular occlusive disease. Transthoracic and/or transesophageal echocardiography serves as a cornerstone in the evaluation, diagnosis, and management of these patients. This article reviews potential cardiac sources of embolism and discusses the role of echocardiography in clinical practice. Recommendations for the use of echocardiography in the diagnosis of cardiac sources of embolism are given including major and minor conditions associated with the risk of embolism., Competing Interests: There are no conflicts of interest.

Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlow's disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: The exact pathomechanism of GNE myopathy remains elusive, but likely involves aberrant sialylation. We explored sialylation status of blood-based glycans as potential disease markers., Methods: We employed immunoblotting, lectin histochemistry and mass spectrometry., Results: GNE myopathy muscle showed hyposialylation of predominantly O-linked glycans. The O-linked glycome of patients' plasma compared with controls showed increased amounts of desialylated Thomsen-Friedenreich (T)-antigen, and/or decreased amounts of its sialylated form, ST-antigen. Importantly, all patients had increased T/ST ratios compared with controls. These ratios were normalized in a patient treated with intravenous immunoglobulins as a source of sialic acid., Discussion:  GNE myopathy clinical trial data will reveal whether T/ST ratios correlate to muscle function. , Conclusion: Plasma T/ST ratios are a robust blood-based biomarker for GNE myopathy, and may also help explain the pathology and course of the disease.