De Chiara Dott.ssa Benedetta

Pubblicazioni su PubMed

• Determinants of invasive left atrial pressure in patients with atrial fibrillation.
  Eur Heart J Cardiovasc Imaging

  2024 Oct;25(11):1590-1598. doi: 10.1093/ehjci/jeae194.
  
  Bonelli Andrea, Degiovanni Anna, Cersosimo Angelica, Spinoni Enrico Guido, Bosco Manuel, Dell'Era Gabriele, Moreo Antonella, De Chiara Benedetta Carla, Gigli Lorenzo, Salghetti Francesca, Arabia Gianmarco, Lombardi Carlo Mario, Brangi Elisa, Giannattasio Cristina, Patti Giuseppe, Curnis Antonio, Metra Marco, Inciardi Riccardo M
  
  Abstract
  
  AIMS:
  Estimation of left ventricular (LV) filling pressures in patients with a history of atrial fibrillation (AF) is challenging due to lack of reliable parameters. This study investigates the association between cardiac structure and function and invasive mean left atrial pressure (LAP).
  
  METHODS AND RESULTS:
  This is a multi-centre prospective study enrolling patients undergoing transcatheter ablation for AF. The invasive measurement of LAP was performed at the time of the procedure while the echocardiography within the previous 24?h. A mean LAP ? 15?mmHg was considered as increased. Overall, 101 patients were included (mean age 65.8 ± 8.5 years, 68% male, mean LV ejection fraction 56.6 ± 8.0%). No significant differences regarding clinical characteristics were detected between the group of patients with normal (n = 47) or increased LAP (n = 54). The latter showed lower values of LV global longitudinal strain, larger left atrial volumes (LAVs) and worse right ventricular (RV) function. After multivariable adjustment, higher E/e' ratio (P = 0.041) and minimal LAV index (LAVI min) (P = 0.031), lower peak atrial longitudinal strain (P = 0.030), and RV free wall longitudinal strain (P = 0.037), but not maximal LAV index (LAVI max) (P = 0.137), were significantly associated with mean LAP. The associations were not modified by cardiac rhythm. Overall, LAVI min showed the best diagnostic accuracy to predict elevated LAP (area under the curve 0.703).
  
  CONCLUSION:
  LA structure and function assessment well correlates with mean LAP in patients with a history of AF. These measures may be used in the assessment of filling pressure in these patients.
  
  © The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site?for further information please contact journals.permissions@oup.com.
  
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• HFPEF and HFA-PEFF scores performance and the additional value of cardiac structure and function in patients with atrial fibrillation.
  Int J Cardiol

  2024 Oct;413():132385. doi: 10.1016/j.ijcard.2024.132385.
  
  Bonelli Andrea, Degiovanni Anna, Beretta Daniele, Cersosimo Angelica, Spinoni Enrico G, Bosco Manuel, Dell'Era Gabriele, De Chiara Benedetta C, Gigli Lorenzo, Salghetti Francesca, Lombardi Carlo M, Arabia Gianmarco, Giannattasio Cristina, Patti Giuseppe, Curnis Antonio, Metra Marco, Moreo Antonella, Inciardi Riccardo M
  
  Abstract
  
  BACKGROUND:
  The HFPEF and the HFA-PEFF scores have become useful tools to diagnose heart failure with preserved ejection fraction (HFpEF). Their accuracy in patients with a history of atrial fibrillation (AF) is less known. This study evaluates the association of these scores with invasive left atrial pressure (LAP) and the additional value of cardiac measures.
  
  METHODS:
  This is a multicenter observational prospective study involving patients undergoing ablation of AF. Patients with left ventricular ejection fraction (LVEF) 
  RESULTS:
  A total of 135 patients were enrolled in the study (mean age 65.2 ± 9.1 years, 32% female, mean LVEF 56.9 ± 7.9%). Patients with HFPEF ? 6 or HFA-PEFF ?5 had higher values of NTproBNP and more impaired cardiac function. However, neither HFPEF nor HFA-PEFF score showed a meaningful association with elevated mean LAP (respectively, OR 1.05 [95%CI 0.83-1.34] p = 0.64, and OR 1.09 [95%CI: 0.86-1.39] p = 0.45). The addition of LA indexed minimal volume (LAVi min) improved the ability of the scores (baseline C-statistic 0.51 [95%CI 0.41-0.61] for the HFPEF score and 0.53 [95%CI 0.43-0.64] for the HFA-PEFF score) to diagnose elevated filling pressure (HFPEF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.005; HFA-PEFF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.02).
  
  CONCLUSION:
  In a cohort of patients with a history of AF, the use of the available diagnostic scores did not predict elevated mean LAP. The integration of LAVi min improved the ability to correctly identify elevated filling pressure.
  
  Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
  
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• The Role of Atrial Cardiopathy as a Potential Cause of Embolic Stroke of Undetermined Source.
  J Stroke

  2024 May;26(2):330-334. doi: 10.5853/jos.2024.00031.
  
  Rizzo Angelo Cascio, Schwarz Ghil, Bonelli Andrea, Di Pietro Andrea, Di Pietro Martina, Aruta Francesco, Motto Cristina, De Chiara Benedetta, Moreo Antonella, Agostoni Elio Clemente
  
  
  
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• Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol.
  High Blood Press Cardiovasc Prev

  2023 Nov;30(6):573-583. doi: 10.1007/s40292-023-00607-z.
  
  Maloberti Alessandro, Intravaia Rita Cristina Myriam, Mancusi Costantino, Cesaro Arturo, Golia Enrica, Ilaria Fucile, Coletta Silvio, Merlini Piera, De Chiara Benedetta, Bernasconi Davide, Algeri Michela, Ossola Paolo, Ciampi Claudio, Riccio Alfonso, Tognola Chiara, Ardissino Maddalena, Inglese Elvira, Scaglione Francesco, Calabrò Paolo, De Luca Nicola, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs.
  
  AIM:
   Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors.
  
  AIM:
  Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors.
  
  METHODS:
  We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers.
  
  CONCLUSIONS:
  Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement.
  
  © 2023. The Author(s).
  
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• Bi-Caval Valve Implantation to Palliate Symptoms in a Case of Massive Tricuspid Regurgitation.
  Cardiovasc Revasc Med

  2023 Aug;53S():S139-S143. doi: 10.1016/j.carrev.2023.01.014.
  
  Galasso Michele, Cartella Iside, Soriano Francesco, Nava Stefano, Tavoletta Pasquale, De Chiara Benedetta, Oliva Fabrizio, Bruschi Giuseppe, Oreglia Jacopo A, Giannattasio Cristina, Mangieri Antonio, Montalto Claudio
  
  Abstract
  
  Severe tricuspid regurgitation is associated with the occurrence of right failure and increased morbidity and mortality. Transcatheter heterotopic bi-caval valve implantation might offer symptom relief in these patients that are often at prohibitive surgical risk.
  
  Copyright © 2023 Elsevier Inc. All rights reserved.
  
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• Prevalence and Rate of Resolution of Left Atrial Thrombus in Patients with Non-Valvular Atrial Fibrillation: A Two-Center Retrospective Real-World Study.
  J Clin Med

  2022 Mar;11(6):. doi: 1520.
  
  Faggiano Pompilio, Dinatolo Elisabetta, Moreo Antonella, De Chiara Benedetta, Sbolli Marco, Musca Francesco, Curnis Antonio, Belli Oriana, Giannattasio Cristina, Tomasi Cesare, Metra Marco, Santangelo Gloria
  
  Abstract
  
  BACKGROUND AND AIM:
  Thromboembolic events due to left atrial appendage (LAA) thrombosis are the main complication of non-valvular atrial fibrillation (NVAF). Although anticoagulants are effective in patients with NVAF, a minimal residual thromboembolic risk persists. Little is known about the prevalence of LAA thrombus and the rate of resolution after the recommended period of anticoagulation therapy, including vitamin K antagonists (VKA), heparin, and non-vitamin K antagonist oral anticoagulants (NOACs).
  
  METHODS AND RESULTS:
  We aimed to study the prevalence of LAA thrombus in an unselected cohort of patients undergoing transesophageal echocardiogram (TEE), and the determinants of LAA thrombus resolution. We retrospectively analyzed 8888 consecutive TEEs performed over five years in two high-volume centers and included all patients with LAA thrombus. A total of 265 patients (3%) had an LAA thrombus. Among these, 97% presented with AF. Fifty-eight percent of patients were on anticoagulants at least three weeks before the diagnosis. After the LAA thrombus diagnosis, VKAs were prescribed in 52%, heparin in 18.5%, and NOAC in 27% of patients. Among the 183 patients with repeat TEE, performed at (25-75th) 39 days (21-84), 67% showed resolution of the LAA thrombus. Although the rate of thrombus resolution was higher in patients treated with NOACs (NOACs 71%, VKA 66%, Heparin 60%) the difference between anticoagulants was statistically non-significant (VKA, OR 0.9, = 0.83; NOAC, OR 1.23, = 0.42; heparin, OR 0.69, = 0.35). Thus, NOACs were demonstrated to be at least as effective as other anticoagulants in the rate of LAA thrombus resolution. Upon multivariate-adjusted analysis, higher LAA emptying velocities were the only predictor of thrombus resolution. In conclusion, the majority of patients were already on anticoagulants. NOACs could be at least as effective as other anticoagulants, yielding an LAA thrombus resolution in two-thirds of patients. This may have clinical relevance, especially in patients undergoing cardioversion or catheter ablation.
  
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• Primary mediastinal large B-cell lymphoma and pregnancy: a challenging clinical scenario.
  Monaldi Arch Chest Dis

  2022 Feb;92(4):. doi: 10.4081/monaldi.2022.2198.
  
  Intravaia Rita, De Chiara Benedetta, Musca Francesco, Casadei Francesca, Santambrogio Gloria, Spanò Francesca, Belli Oriana, Quattrocchi Giuseppina, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  A 26-weeks pregnant woman presented with progressively worsening dyspnoea and poor general conditions. Using low-dose radiation multi-imaging techniques and thoracic biopsy a primary mediastinal large B cell was diagnosed. A multidisciplinary approach identified the correct hemodynamic management, the best therapeutic strategy and the timing for delivery.
  
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• Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.
  J Hum Hypertens

  2022 Jul;36(7):610-616. doi: 10.1038/s41371-021-00604-6.
  
  Maloberti Alessandro, Rebora Paola, Occhino Giuseppe, Alloni Marta, Musca Francesco, Belli Oriana, Spano Francesca, Santambrogio Gloria Maria, Occhi Lucia, De Chiara Benedetta, Casadei Francesca, Moreo Antonella, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (
  © 2021. The Author(s), under exclusive licence to Springer Nature Limited.
  
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• Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.
  Nutr Metab Cardiovasc Dis

  2021 May;31(5):1501-1508. doi: 10.1016/j.numecd.2021.01.023.
  
  Maloberti Alessandro, Bossi Irene, Tassistro Elena, Rebora Paola, Racioppi Angelo, Nava Stefano, Soriano Francesco, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo, Vallerio Paola, Pirola Roberto, De Chiara Benedetta, Oliva Fabrizio, Moreo Antonella, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIMS:
  Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation.
  
  METHODS AND RESULTS:
  231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function.
  
  CONCLUSIONS:
  In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.
  
  Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects.
  Nutr Metab Cardiovasc Dis

  2021 Apr;31(4):1044-1052. doi: 10.1016/j.numecd.2020.11.011.
  
  Maloberti Alessandro, Bombelli Michele, Vallerio Paola, Milani Martina, Cartella Iside, Tavecchia Giovanni, Tognola Chiara, Grasso Enzo, Sun Jinwei, De Chiara Benedetta, Riccobono Salvatore, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND AIMS:
  Metabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls.
  
  METHODS AND RESULTS:
  We enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p 
  CONCLUSIONS:
  the main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.
  
  Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors.
  Radiother Oncol

  2020 Nov;152():146-150. doi: 10.1016/j.radonc.2020.07.004.
  
  Vallerio Paola, Maloberti Alessandro, Palazzini Matteo, Occhi Lucia, Peretti Alessio, Nava Stefano, Soriano Francesco, Musca Francesco, De Chiara Benedetta, Belli Oriana, Moreo Antonella, Bisceglia Irma, Lestuzzi Chiara, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5-10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group.
  
  DESIGN AND METHODS:
  A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group.
  
  RESULTS:
  The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p 
  CONCLUSIONS:
  Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• [Clinical and diagnostic key points of left ventricular hypertrophy in adults: insights from the ANMCO Lombardy experience].
  G Ital Cardiol (Rome)

  2020 Jun;21(6):447-456. doi: 10.1714/3359.33329.
  
  Iacovoni Attilio, De Chiara Benedetta, Sormani Paola, Campana Marco, Agostini Francesco, Faggiano Pompilio, Occhi Lucia, Dadone Viola, Raineri Claudia, Moreo Antonella, Di Tano Giuseppe,
  
  Abstract
  
  Left ventricular hypertrophy is a common complication of different diseases. Among these, cardiac involvement of amyloidosis or Anderson-Fabry disease are often unrecognized. Early diagnosis is therefore crucial because new therapies can impact the progression of these diseases. Different specific signs unmasked by clinical, laboratory, and non-invasive diagnostic tests such as echocardiography or cardiac magnetic resonance could guide clinicians towards an appropriate diagnosis. The aim of this review is to underline the major diagnostic clues of different forms of left ventricular hypertrophy in adult patients, guiding clinicians towards a more appropriate diagnosis.
  
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• Update on the Organizational Aspects of Echocardiography in Italy (From Operator Training to the Report: 2007-2019): A Consensus Document by the "Società Italiana di Ecocardiografia e CardioVascular Imaging" Accreditation Area and Board 2017-2019.
  J Cardiovasc Echogr

  2019 ;29(4):133-138. doi: 10.4103/jcecho.jcecho_61_19.
  
  Monte Ines Paola, De Chiara Benedetta, Demicheli Gloria, Aragona Pierluigi, Ancona Roberta, Antonini-Canterin Francesco, Citro Rodolfo, Colonna Paolo, Giorgi Mauro, Mantero Antonio Giuseppe, Manuppelli Vincenzo, Petrella Licia, Posteraro Alfredo, Benedetto Frank
  
  Abstract
  
  In 2007, Società Italiana di Ecocardiografia e CardioVascular Imaging (SIECVI) already SIEC, published the document on the organization of echocardiography in Italy. In the years following the technological evolution, cultural and health factors have changed "the way, we do echo" as a tool for the different clinical pathways. The SIECVI Accreditation Area and Board 2017-2019 considered necessary to review and update the document in the light of innovation in the application of ultrasound for the heart disease assessment. In the document, we have considered the role of SIECVI in multimodal imaging, the need of training and certification of operators, the quality of echo machines, the accreditation of laboratories, the compilation of the report and its responsibility, and the presence of the sonographers in the EchoLab.
  
  Copyright: © 2020 Journal of Cardiovascular Echography.
  
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• [ANMCO/SICI-GISE/SIC/SIECVI/SIRM Consensus document: Appropriateness of multimodality imaging in cardiovascular disease].
  G Ital Cardiol (Rome)

  2020 Jan;21(1):34-88. doi: 10.1714/3285.32588.
  
  Nardi Federico, Pino Paolo Giuseppe, Gabrielli Domenico, Colivicchi Furio, Abrignani Maurizio Giuseppe, Amico Antonio Francesco, Aspromonte Nadia, Benedetto Francesco Antonio, Bertella Erika, Boccardi Lidia Maria, Bucciarelli Ducci Chiara, Caldarola Pasquale, Campana Marco, Caso Pio, Citro Rodolfo, Costante Anna Maria, De Chiara Benedetta Carla, Di Cesare Ernesto, Di Fusco Stefania Angela, Domenicucci Stefano, Enea Iolanda, Erba Paola, Faganello Giorgio, Favilli Silvia, Geraci Giovanna, Giubbini Raffaele, Giunta Nicola, Guido Vincenzo, Imazio Massimo, Khoury Georgette, La Canna Giovanni, Mele Donato, Moreo Antonella Maurizia, Mercuro Giuseppe Guglielmo, Musumeci Giuseppe, Neglia Danilo, Parrini Iris, Pinamonti Bruno, Pollarolo Luigi, Pontone Gianluca, Privitera Carmelo, Riccio Carmine, Sinagra Gianfranco, Urbinati Stefano, Varbella Ferdinando, Berisso Massimo Zoni, Zuin Guerrino, Di Lenarda Andrea, Gulizia Michele Massimo
  
  Abstract
  
  The complexity of cardiovascular diseases has led to an extensive use of technological instruments and the development of multimodality imaging. This extensive use of different cardiovascular imaging tests in the same patient has increased costs and waiting times.The concept of appropriateness has changed over time. Appropriateness criteria address the need for specific cardiovascular imaging tests in well-defined clinical scenarios, and define the kind of cardiovascular imaging that is appropriated for each clinical scenario in different stages of the disease. The concept of appropriateness criteria has replaced the old idea of appropriate use criteria and reflects the increasing effort of the international Scientific Societies to create and review in a critical way the management of diagnostic tests used by clinicians.The aim of this Italian consensus document is to address the use of multimodality imaging in the diagnosis and management of the major cardiovascular clinical scenarios, taking into consideration not only the international guidelines and scientific documents already published, but also the reality of Italian laws as well as the various professional profiles involved in patient management and availability of technological diagnostic instruments.
  
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• [Role of multimodality imaging in the clinical evaluation of hypertrophic cardiomyopathy].
  G Ital Cardiol (Rome)

  2019 Dec;20(12):746-761. doi: 10.1714/3271.32383.
  
  Guido Vincenzo, Campana Marco, Pino Paolo Giuseppe, Moreo Antonella, De Chiara Benedetta, Bertella Erika, Khoury Georgette,
  
  Abstract
  
  Sarcomeric hypertrophic cardiomyopathy is the most common cardiovascular genetic disease. Clinical evaluation and comprehensive echocardiography are crucial for the diagnosis and early evaluation of the hypertrophic phenotype, but multimodality imaging approach is often required to better define diagnosis and differential diagnosis from phenocopies. This review aims to assess the role of multimodality imaging and, in particular, advanced echocardiography and cardiac magnetic resonance in relation to differential diagnosis and preclinical diagnosis, identification of different phenotypes, and assessment of disease progression and risk of sudden cardiac death. A multimodality imaging approach is also crucial for the selection of patients amenable to surgical or percutaneous septal myectomy and for guiding both procedures.
  
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• Sequencing of NOTCH1 gene in an Italian population with bicuspid aortic valve: Preliminary results from the GISSI OUTLIERS VAR study.
  Gene

  2019 Oct;715():143970. doi: 10.1016/j.gene.2019.143970.
  
  Pileggi Silvana, De Chiara Benedetta, Magnoli Michela, Franzosi Maria Grazia, Merlanti Bruno, Bianchini Francesca, Moreo Antonella, Romeo Gabriella, Russo Claudio Francesco, Rizzo Stefania, Basso Cristina, Martinelli Luigi, Maseri Attilio,
  
  Abstract
  
  BACKGROUND:
  Bicuspid aortic valve (BAV) formation is genetically determined, with reduced penetrance and variable expressivity. NOTCH1 is a proven candidate gene and its mutations have been found in familial and sporadic cases of BAV.
  
  METHODS:
  66 BAV patients from the GISSI VAR study were genotyped for the NOTCH1 gene.
  
  RESULTS:
  We identified 63 variants, in heterozygous and homozygous states. Fifty-two are common polymorphisms present in almost all patients. Eleven variants are new and never yet reported: two are non-synonymous substitutions, Gly540Asp in exon 10 and Glu851Gln in exon 16; one is in the 3'UTR region and seven in introns, one corresponds to a T allele insertion in intron 27. We selected four statistically noteworthy and seven new variants identified in six BAV patients and correlated them with clinical and demographic variables and with imaging and histological parameters. Preliminary data show that four were BAV patients with isolated stenosis in patients over 60 aged. These variants may correlate with a later need for surgery for the presence of stenosis and not aortic valve regurgitation or ascending aortic aneurysm.
  
  CONCLUSIONS:
  Completing the genotyping of 62 BAV patients we found 11 new variants in the NOTCH1 gene never yet reported. These findings confirm that the identification of new, clinically remarkable biomarkers for BAV requires a deeper genetic understanding of the NOTCH1 gene variants, which could be targeted by future diagnostic and therapeutic strategies.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• Could two-dimensional radial strain be considered as a novel tool to identify pre-clinical hypertrophic cardiomyopathy mutation carriers?
  Int J Cardiovasc Imaging

  2019 Dec;35(12):2167-2175. doi: 10.1007/s10554-019-01668-9.
  
  Santambrogio Gloria Maria, Maloberti Alessandro, Vallerio Paola, Peritore Angelica, Spanò Francesca, Occhi Lucia, Musca Francesco, Belli Oriana, De Chiara Benedetta, Casadei Francesca, Facchetti Rita, Turazza Fabio, Manfredini Emanuela, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18%?±?9.6 vs. 44.59%?±?12.67 respectively; p-value?0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.
  
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• Pulse wave velocity progression over a medium-term follow-up in hypertensives: Focus on uric acid.
  J Clin Hypertens (Greenwich)

  2019 Jul;21(7):975-983. doi: 10.1111/jch.13603.
  
  Maloberti Alessandro, Rebora Paola, Andreano Anita, Vallerio Paola, De Chiara Benedetta, Signorini Stefano, Casati Marco, Besana Silvia, Bombelli Michele, Grassi Guido, Valsecchi Maria Grazia, Giannattasio Cristina
  
  Abstract
  
  The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P 
  ©2019 Wiley Periodicals, Inc.
  
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• Impact of serial echocardiography in the management of primary cardiac lymphoma.
  J Saudi Heart Assoc

  2018 Apr;30(2):160-163. doi: 10.1016/j.jsha.2017.08.001.
  
  Cereda Alberto Francesco, Moreo Antonella Maurizia, Sormani Paola, De Chiara Benedetta, Casadei Francesca, Zancanella Michelle, Rusconi Chiara, Cairoli Roberto, Giannattasio Cristina
  
  
  
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• Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.
  Nutrition

  2017 Jun;38():41-47. doi: 10.1016/j.nut.2016.12.018.
  
  Campolo Jonica, Bernardi Stefano, Cozzi Lorena, Rocchiccioli Silvia, Dellanoce Cinzia, Cecchettini Antonella, Tonini Annamaria, Parolini Marina, De Chiara Benedetta, Micheloni Gianpaolo, Pelosi Gualtiero, Passino Claudio, Giannattasio Cristina, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF).
  
  METHODS:
  We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000.
  
  RESULTS:
  In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (?1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively).
  
  CONCLUSIONS:
  Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Clinical imaging in patients with fever and suspected endocarditis.
  Minerva Cardioangiol

  2017 Dec;65(6):629-637. doi: 10.23736/S0026-4725.17.04423-1.
  
  DE Chiara Benedetta, Moreo Antonella
  
  Abstract
  
  Echocardiography remains the cornerstone of the diagnostic of anatomic lesions and consequences on cardiac function caused by infective endocarditis (IE). There is now evidence that other imaging techniques are useful in reducing the number of non-conclusive diagnoses, in particular when IE is suspected on prosthetic material or devices. Besides diagnosis, cardiac imaging strongly contributes to prognostic assessment, indications for early surgery and patient follow-up. It is required a specific expertise for implementing and interpreting all imaging techniques and the complexity of decision-making highlights the need for a multidisciplinary management of difficult cases in specialized endocarditis teams.
  
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• HeartWare-HVAD for end-stage heart failure: a review of clinical experiences with ?50 patients.
  Expert Rev Med Devices

  2017 Jun;14(6):423-437. doi: 10.1080/17434440.2017.1325318.
  
  Botta Luca, De Chiara Benedetta, Macera Francesca, Cannata Aldo, Costetti Alessandro, Voltolini Alessandra, Moreo Antonella, Cipriani Manlio, Frigerio Maria, Russo Claudio Francesco
  
  Abstract
  
  Despite the improvements in medical and surgical treatments, the incidence of end-stage heart failure (ESHF) continues to increase. Different mechanical systems have been adopted to support failing left ventricles. Among continuous-flow devices, the HeartWare-HVAD was the first to use a centrifugal pump rather than an axial one. Areas covered: In this review article, we provide an overview of the HeartWare-HVAD as a ventricular assist device for ESHF, discussing indications, echocardiographic assessment, surgical techniques, outcomes, concerns and controversies. Scientific literature was reviewed with a MEDLINE search strategy combining 'HeartWare' or 'HVAD' with 'heart failure'. A total of 263 papers were found using the reported search. From these, 16 were identified to provide the best evidence on the subject reporting outcomes in ?50 patients. Expert commentary: HeartWare-HVAD is a minute device that provides full circulatory support in patients with ESHF. Its main indication remains bridge to heart transplantation (HTx). Median sternotomy is the preferred technique of implantation although less invasive procedures have been described. Early outcomes are satisfactory. Nevertheless, some fearing complications still occur during the mid- and long-term follow-up. Further technical developments and optimal medical management will guarantee better outcomes.
  
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• Late Echocardiographic Study of Aortic Valve and Aortic Root after Surgery for Type A Acute Aortic Dissection.
  J Cardiovasc Echogr

  2016 ;26(3):78-82. doi: 10.4103/2211-4122.187948.
  
  Molteni Martina, De Chiara Benedetta, Casadei Francesca, Botta Luca, Merlanti Bruno, Russo Claudio Francesco, Giannattasio Cristina, Moreo Antonella
  
  Abstract
  
  OBJECTIVE:
  In case of concomitant aortic regurgitation (AR) valve, sparing operation is considered the first choice in selected patients. The aim of this retrospective clinical and echocardiographic study was to evaluate the long-term survival results of conservative approach and the determinants of recurrent AR.
  
  METHODS:
  From 2000 to 2011, fifty patients (median: 63 years and interquartile range: 53-72) underwent an aortic valve-sparing procedure for acute aortic dissection, and discharged alive. The long-term clinical and echocardiographic outcome was analyzed.
  
  RESULTS:
  Late all-causes mortality was 18% (nine patients) at a median follow-up of 55.8 months. Ten patients (20%) underwent re-operations, five of them for aortic valve/root recurrent disease; freedom from proximal re-operation was 90%. Two-third of the patients had a preoperative AR grade
  CONCLUSIONS:
  Preoperative AR and late aortic root diameter were not the predictors of late AR. Late AR is higher in patients who underwent aortic commissures and cusps resuspension compared to the only replacement of the ascending aorta.
  
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• Mitral periprosthetic leakage: contemporary results of surgical correction at a single centre.
  Interact Cardiovasc Thorac Surg

  2017 Aug;25(2):185-190. doi: 10.1093/icvts/ivx101.
  
  Botta Luca, De Chiara Benedetta, Quattrocchi Salvina, Casadei Francesca, Borgia Francesco, Giannattasio Cristina, Moreo Antonella, Russo Claudio Francesco
  
  Abstract
  
  OBJECTIVES:
  Mitral periprosthetic leakage (PPL) is a serious complication following valve replacement. Conflicting outcomes of surgical treatment have been reported in the presence of multiple previous cardiac operations and associated co-pathological conditions.
  
  METHODS:
  Sixty-five symptomatic patients (37 women, mean age 64.8 years) underwent conventional operations at our hospital from 2006 to 2015. Mitral PPL was the leading surgical indication, although associated procedures were included. Previous transcatheter procedures and leaks involving multiple prostheses were excluded. The median number of past mitral operations was 2 (range 1-5). PPL recurrence was observed in 29% of cases. A previous operation on the aortic or tricuspid valve was performed in 31 patients.
  
  RESULTS:
  Mitral PPL involved one-, two- or three-quarters of the mitral perimeter in 46, 43 and 11% of cases. Prosthetic refixation or replacement was performed in 24 and 41 patients, respectively. Annular reconstruction was necessary in 17% of prosthetic replacements. Associated procedures were performed in 19 patients. The operation was executed through a right minithoracotomy (unclamped aorta) in 20% of patients. In-hospital deaths occurred in 3.1%. After a median follow-up of 60 months, freedom from all-cause mortality was 96.8, 91.5 and 88.8% at 1, 3 and 5 years. Lateral leaks [P?=?0.03; hazard ratio (HR)?=?4.57, 95% confidence interval (CI): 1.13-18.3] and PPL relapse (P?=?0.03; HR?=?4.33, 95% CI: 1.12-16.7) were independently associated with death. At follow-up, 4 patients had a?>2+ recurrent leak and 2 were reoperated.
  
  CONCLUSIONS:
  A customized conventional mitral reoperation still represents a satisfactory and effective treatment option for PPL and should be considered even in patients with very complex issues.
  
  © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• Infective endocarditis of an aortic intimal flap due to Streptococcus agalactiae in a patient with Sjögren's syndrome: an unusual clinical case report.
  Echocardiography

  2016 Sep;33(9):1434-5. doi: 10.1111/echo.13274.
  
  De Chiara Benedetta, Peritore Angelica, Sara Roberto, Giannattasio Cristina, Moreo Antonella
  
  
  
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• [Highlights from the 2015 ESC guidelines for the management of infective endocarditis].
  G Ital Cardiol (Rome)

  2016 Apr;17(4):245-7. doi: 10.1714/2214.23892.
  
  De Chiara Benedetta, Gerometta Piersilvio
  
  
  
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• Asymptomatic aortic mural thrombus in a minimally atherosclerotic vessel.
  Interact Cardiovasc Thorac Surg

  2016 Mar;22(3):371-3. doi: 10.1093/icvts/ivv349.
  
  Maloberti Alessandro, Oliva Fabrizio, De Chiara Benedetta, Giannattasio Cristina
  
  Abstract
  
  Aortic mural thrombi in a normal (non-aneurysmal or minimally atherosclerotic) vessel are an uncommon condition. They are usually located in the descending aorta and, less frequently, in the aortic arch or in the abdominal aorta. The typical clinical presentation is the appearance of symptoms/signs of peripheral arterial embolization, such as lower limb or visceral ischaemia, but these can also be accidentally found in asymptomatic patients. We report the case of a 40-year old man with untreated hypertension and dyslipidaemia admitted to hospital for atypical chest pain associated with an elevation in high-sensitivity troponin T with normal creatine kinase isoenzime MB creatine kinase isoenzyme. Elektrocardiogram (EKG) and transthoracic echocardiography were non-diagnostic; in order to exclude an aortic dissection, a gated chest computed tomography was performed and showed an aortic thrombus on a minimally atherosclerotic wall. Then, a transoesophageal echocardiography confirmed an aortic floating thrombus (7 × 4 mm). Cardiac surgeons advised against surgery and therapy with antiplatelet, low molecular weight heparin, ?-blocker, antihypertensive and lipid-lowering drugs was initiated. A complete resolution of the thrombus was observed at the 12-day tomographic control.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• St. Jude Medical Trifecta aortic valve: results from a prospective regional multicentre registry.
  J Cardiothorac Surg

  2015 Nov;10():169. doi: 169.
  
  Mariscalco Giovanni, Mariani Silvia, Bichi Samuele, Biondi Andrea, Blasio Andrea, Borsani Paolo, Corti Fabrizio, De Chiara Benedetta, Gherli Riccardo, Leva Cristian, Russo Claudio Francesco, Tasca Giordano, Vanelli Paolo, Alfieri Ottavio, Antona Carlo, Di Credico Germano, Esposito Giampiero, Gamba Amando, Martinelli Luigi, Menicanti Lorenzo, Paolini Giovanni, Beghi Cesare
  
  Abstract
  
  BACKGROUND:
  The Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a stented pericardial heart valve with excellent preliminary results. Aim of the study was to evaluate its early clinical and hemodynamic performances in a multicenter regional registry.
  
  METHODS:
  Between January 2011 and June 2012, 178 consecutive patients undergoing aortic valve replacement with the Trifecta bioprosthesis were prospectively enrolled at 9 Italian centers. Clinical and echocardiographic data were collectedat discharge, 6-months and at 1-year postoperatively.
  
  RESULTS:
  The average age was 75.4?±?7.7 years,and 95 (53 %) were men. Indication for valve replacement included stenosis in 123 patients (69 %), mixed lesions in 25 (14 %), and regurgitation in 30 (17 %). Ninety-three (52 %) patients were in NYHA functional class III/ IV. Hospital mortality accounted for 5 (2.8 %) patients. No valve-related perioperative complications were encountered. Median follow-up was 20.5 months (range: 1-34). Early (?6 months) complications included one thromboembolic event, one major bleeding, and 3 endocarditis (2 explants). Two late (>6 months) thromboembolic events and two endocarditis (1 explant) were registered. No valve thrombosis or structural deterioration were observed after discharge. At 30-months, freedom from all-cause mortality was 87 %, freedom from valve-related mortality 99.4 %, freedom from endocarditis 97.5 %, and freedom from valve explants 98 %. At 1-year, mean gradients ranged from 8 to 16 mmHg, and effective orifice area indexes from 1.0 to 1.2 cm(2)/m(2) for valve sizes from 19 to 27 mm, respectively. No patients had severe prosthesis-patient mismatch.
  
  CONCLUSIONS:
  Trifecta bioprosthesis provided favourable clinical and hemodynamic results over time.
  
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• Mitral valve endocarditis due to Abiotrophia defectiva in a 14th week pregnant woman.
  Interact Cardiovasc Thorac Surg

  2016 Jan;22(1):112-4. doi: 10.1093/icvts/ivv289.
  
  Botta Luca, Merati Roberto, Vignati Gabriele, Orcese Carlo Andrea, De Chiara Benedetta, Cannata Aldo, Bruschi Giuseppe, Fratto Pasquale
  
  Abstract
  
  Infective endocarditis during pregnancy carries a high mortality risk, both for the mother and for the foetus and requires a multidisciplinary team in the management of complicated cases. We report our experience with a 39-year old patient, affected by an acute active mitral endocarditis due to Abiotrophia defectiva at the 14th gestational week, strongly motivated to continue the pregnancy. Our patient successfully underwent mitral valve replacement with a normothermic high-flow cardiopulmonary bypass under continuous intraoperative foetal monitoring. Caesarean section occurred at the 38th gestational week. The delivery was uneventful and both the mother and child are doing well at the 16-month follow-up.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• [Syncope: an untreated symptom with a lifesaving intervention].
  G Ital Cardiol (Rome)

  2015 Sep;16(9):517-8. doi: 10.1714/1988.21532.
  
  Giupponi Luca, De Chiara Benedetta, Spanò Francesca, Giannattasio Cristina, Taglieri Corrado, Moreo Antonella
  
  Abstract
  
  We report the case of a 61-year-old woman referred to our center for cardiac evaluation after a syncope, with echocardiographic findings of a papillary fibroelastoma on the edge of the non-coronary aortic cusp. The three-dimensional transesophageal approach provided a unique understanding of the size and shape of the mass and it favorably directed the surgeon towards treatment with conservative surgery.
  
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• [The conundrum of therapeutic management in acute myocardial infarction complicated by endoventricular thrombosis: moving between different risks].
  G Ital Cardiol (Rome)

  2015 ;16(7-8):437-41. doi: 10.1714/1954.21248.
  
  Varrenti Marisa, Morici Nuccia, De Chiara Benedetta, Oreglia Jacopo Andrea, Pedrotti Patrizia, Giannattasio Cristina, Klugmann Silvio, Roghi Alberto
  
  Abstract
  
  Coronary artery disease is a rare entity in young patients and accurate assessment of its prevalence is difficult. Although coronary artery disease is frequently a silent process, it may also acutely present with myocardial infarction (MI). One of the most feared complications of MI is left ventricular thrombus formation. Transthoracic echocardiography is recommended for all patients with MI, and cardiac magnetic resonance should be considered because of its higher sensitivity if thrombus cannot clearly be demonstrated. The optimal treatment is based on anticoagulant therapy that should be started early and maintained for 3-4 months after the index event. We report the case of a 35-year-old male patient with anterior MI, complicated by left ventricular thrombus formation, extensive edema, microvascular obstruction and hemorrhagic core of the apical septum on cardiac magnetic resonance assessment.
  
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• Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve patients: prospective longitudinal, multicenter study to investigate correlation between surgical, echo distinctive features, histologic and genetic findings in phenotypically homogeneous outlier cases.
  Int J Cardiol

  2015 Nov;199():180-5. doi: 10.1016/j.ijcard.2015.06.182.
  
  Merlanti Bruno, De Chiara Benedetta, Maggioni Aldo Pietro, Moreo Antonella, Pileggi Silvana, Romeo Gabriella, Russo Claudio Francesco, Rizzo Stefania, Martinelli Luigi, Maseri Attilio,
  
  Abstract
  
  BACKGROUND/OBJECTIVES:
  Bicuspid aortic valve (BAV) is the most common congenital heart disorder, affecting up to 2% of the population. Involvement of aortic root and ascending aorta (aneurysm or, eventually, dissection) is frequent in patients with pathologic or normal functioning BAV. Unfortunately, there are no well-known correlations between valvular and vascular diseases. In VAR protocol, with a new strategy of research, we analysemultiple aspects of BAV disease through correlation between surgical, echo, histologic and genetic findings in phenotypically homogeneous outlier cases.
  
  METHODS:
  VAR protocol is a prospective, longitudinal, multicenter study. It observes 4 homogeneous small groups of BAV surgical patients (15 patients each): isolated aortic regurgitation, isolated ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm, isolated aortic stenosis in older patients (>60years). Echo analysis is extended to first-degree relatives and, in case of BAV, genetic test is performed. Patients and relatives are enrolled in 10 cardiac surgery/cardiologic centers throughout Italy.
  
  CONCLUSIONS:
  The aim of the study is to identify predictors of favorable or unfavorable evolution of BAV in terms of valvular dysfunction and/or aortic aneurysm. Correlations between different features could help in identification of various BAV risk groups, rationalizing follow-up and treatment.
  
  Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
  
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• Clinical impact and evolution of mitral regurgitation following transcatheter aortic valve replacement: a meta-analysis.
  Heart

  2015 Sep;101(17):1395-405. doi: 10.1136/heartjnl-2014-307120.
  
  Nombela-Franco Luis, Eltchaninoff Hélène, Zahn Ralf, Testa Luca, Leon Martin B, Trillo-Nouche Ramiro, D'Onofrio Augusto, Smith Craig R, Webb John, Bleiziffer Sabine, De Chiara Benedetta, Gilard Martine, Tamburino Corrado, Bedogni Francesco, Barbanti Marco, Salizzoni Stefano, García del Blanco Bruno, Sabaté Manel, Moreo Antonella, Fernández Cristina, Ribeiro Henrique Barbosa, Amat-Santos Ignacio, Urena Marina, Allende Ricardo, García Eulogio, Macaya Carlos, Dumont Eric, Pibarot Philippe, Rodés-Cabau Josep
  
  Abstract
  
  OBJECTIVES:
  Mitral regurgitation (MR) is a common entity in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but its influence on outcomes remains controversial. The purpose of this meta-analysis was to assess the clinical impact of and changes in significant (moderate-severe) MR in patients undergoing TAVR, overall and according to valve design (self-expandable (SEV) vs balloon-expandable (BEV)).
  
  METHODS:
  All national registries and randomised trials were pooled using meta-analytical guidelines to establish the impact of moderate-severe MR on mortality after TAVR. Studies reporting changes in MR after TAVR on an individual level were electronically searched and used for the analysis.
  
  RESULTS:
  Eight studies including 8015 patients (SEV: 3474 patients; BEV: 4492 patients) were included in the analysis. The overall 30-day and 1-year mortality was increased in patients with significant MR (OR 1.49, 95% CI 1.16 to 1.92; HR 1.32, 95% CI 1.12 to 1.55, respectively), but a significant heterogeneity across studies was observed (p
  CONCLUSIONS:
  Concomitant moderate-severe MR was associated with increased early and late mortality following TAVR. A significant improvement in MR severity was detected in half of the patients following TAVR, and the degree of improvement was greater in those patients who had received a BEV.
  
  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
  
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• Italian multicentre study on type A acute aortic dissection: a 33-year follow-up?.
  Eur J Cardiothorac Surg

  2016 Jan;49(1):125-31. doi: 10.1093/ejcts/ezv048.
  
  Russo Claudio F, Mariscalco Giovanni, Colli Andrea, Santè Pasquale, Nicolini Francesco, Miceli Antonio, De Chiara Benedetta, Beghi Cesare, Gerosa Gino, Glauber Mattia, Gherli Tiziano, Nappi Gianantonio, Murzi Michele, Molardi Alberto, Merlanti Bruno, Vizzardi Enrico, Bonadei Ivano, Coletti Giuseppe, Carrozzini Massimiliano, Gelsomino Sandro, Caiazzo Antonio, Lorusso Roberto
  
  Abstract
  
  OBJECTIVES:
  Despite substantial progress in surgical techniques and perioperative management, the treatment and long-term follow-up of type A acute aortic dissection (AAD) still remain a major challenge. The objective of this retrospective, multicentre study was to assess in a large series of patients the early and long-term results after surgery for type A AAD.
  
  METHODS:
  We analysed the preoperative, intraoperative and postoperative conditions of 1.148 consecutive patients surgically treated in seven large referral centres from 1981 to 2013. We applied to each patient three different multi-parameter risk profiles (preadmission risk, admission risk and post-surgery risk) in order to compare risk factors and outcome. Long-term Kaplan-Meier survival was evaluated.
  
  RESULTS:
  The median age was 64 years and the male population was predominant (66%). Identified diagnosis of collagen disease was present in 9%, and Marfan syndrome in 5%. Bicuspid aortic valve was present in 69 patients (6%). Previous cardiac surgery was identified in 10% of the patients. During surgery, the native aortic valve was preserved in 72% of the cases, including leaflet resuspension in 23% and David operation in 1.2%. Considering aortic valve replacement (AVR: 28%), bioprosthesis implantation was performed in 14.7% of the subjects. Neurological impairment at discharge was shown in 23% of the cases among which 21% of patients had new neurological impairment versus preoperative conditions. The overall 30-day mortality rate was 25.7%. All risk profiles remained independently associated with in-hospital mortality. During the available follow-up of hospital survivors (median: 70 months, interquartile range: 34-113, maximum: 396), cardiac-related death occurred in 7.9% of the subjects. The cumulative survival rate for cardiac death was 95.3% at 5 years, 92.8% at 10 years and 52.8% at 20 years. Severe aortic regurgitation (AR) (grade 3-4) at the time of surgery showed to be a significant risk factor for reintervention during the follow-up (P
  CONCLUSIONS:
  Although surgery for type A has remained challenging over more than three decades, there is a positive trend in terms of hospital mortality and long-term follow-up. About 90% of patients were free from reoperation in the long term, although late AR remains a critical issue, suggesting that a thorough debate on surgical options, assessment and results of a conservative approach should be considered.
  
  © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
  
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• [Right ventricular dysfunction in advanced heart failure].
  G Ital Cardiol (Rome)

  2014 ;15(7-8):430-40. doi: 10.1714/1596.17420.
  
  Cipriani Manlio, De Chiara Benedetta, Ammirati Enrico, Roghi Alberto, D'Angelo Luciana, Oliva Fabrizio, Moreo Antonella, Bonacina Edgardo, Martinelli Luigi
  
  Abstract
  
  The role of the right ventricle has often been underestimated in heart failure. It has been thought that the right cavity has a less prominent impact on symptoms, therapeutic approach, and prognosis. Right ventricular dysfunction is a complex issue and its diagnosis has acquired a relevant role, in particular with the improvement of new therapeutic options such as ventricular assist devices. The complex geometry of the right ventricle and its interaction with the left ventricle are still a matter of debate, leaving several open questions about the best therapeutic approach to manage right ventricular dysfunction. Echocardiography remains the first-line imaging technique, but an integrated multimodality evaluation with clinical, biochemical and hemodynamic parameters, and cardiovascular magnetic resonance imaging can provide a more comprehensive way to choose the most appropriate treatment for patients with heart failure associated with right ventricular dysfunction.
  
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• Left ventricular or Bi-ventricular assist device? How dobutamine stress echocardiography can untie the dilemma of right ventricular dysfunction.
  Int J Cardiol

  2014 Nov;177(1):e6-8. doi: 10.1016/j.ijcard.2014.07.194.
  
  Ammirati Enrico, Cipriani Manlio, De Chiara Benedetta, D'Angelo Luciana, Belli Oriana, Moreo Antonella, Oliva Fabrizio, Martinelli Luigi, Frigerio Maria
  
  
  
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• Aortic valve sclerosis as a marker of coronary artery atherosclerosis; a multicenter study of a large population with a low prevalence of coronary artery disease.
  Int J Cardiol

  2014 Mar;172(2):364-7. doi: 10.1016/j.ijcard.2014.01.024.
  
  Rossi Andrea, Gaibazzi Nicola, Dandale Raje, Agricola Eustachio, Moreo Antonella, Berlinghieri Nicola, Sartorio Daniele, Loffi Marco, De Chiara Benedetta, Rigo Fausto, Vassanelli Corrado, Faggiano Pompilio
  
  Abstract
  
  UNLABELLED:
  There are no studies analyzing the association between aortic valve sclerosis (AVS) and coronary artery disease (CAD) in a large and multicenter patient population with an overall low prevalence of CAD. We hypothesized that AVS could predict the presence and degree of CAD in patients with severe organic mitral regurgitation.
  
  METHODS:
  We retrospectively analyzed consecutive patients with flail mitral leaflet who had coronary angiography for pre-surgical screening and not because suspect of CAD. End-points were considered: 1) any degree of CAD (stenosis>20%) and 2) obstructive CAD (stenosis>75% of at least one coronary artery). AVS was defined as focal areas of increased echogenicity and thickening of the leaflets. Traditional clinical risk factors were considered: age, male gender, hypertension (>140/90 mmHg or medical therapy), hypercholesterolemia (total cholesterol>200 mg/dl or statin), diabetes, family history of CAD and smoking habit.
  
  RESULTS:
  675 patients (mean age: 64±12; 27% female) formed the study population. Among patients with AVS, 60% and 39% had any-CAD and ob-CAD respectively, on the opposite among patients without AVS 12% and 7% had any-CAD and ob-cad. After adjustment for clinical risk factors, AVS was associated with a 22.7 fold increased risk of any degree of CAD (95% CI 8.1 63.6 p
  CONCLUSION:
  In a large and multicenter sample of patient with flail mitral leaflet, AVS was strongly associated with the presence and degree of CAD independently of clinical risk factors.
  
  Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
  
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• Response to letter to the editor by Rui Baptista, M.D., Rogério Teixeira, M.D.
  Am Heart J

  2013 Sep;166(3):e15-6. doi: 10.1016/j.ahj.2013.06.015.
  
  Gargani Luna, Agoston Gergely, Pignone Alberto Moggi, Moreo Antonella, Badano Luigi P, Bazzichi Laura, Costantino Marco Fabio, Pieri Francesco, Epis Oscar, Bruschi Eleonora, De Chiara Benedetta, Mori Fabio, Bombardieri Stefano, Cerinic Marco Matucci, Bossone Eduardo, Picano Eugenio
  
  
  
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• Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: a multicenter study.
  Am Heart J

  2013 Feb;165(2):200-7. doi: 10.1016/j.ahj.2012.10.020.
  
  Gargani Luna, Pignone Alberto, Agoston Gergely, Moreo Antonella, Capati Eugenia, Badano Luigi P, Doveri Marica, Bazzichi Laura, Costantino Marco Fabio, Pavellini Andrea, Pieri Francesco, Musca Francesco, Muraru Denisa, Epis Oscar, Bruschi Eleonora, De Chiara Benedetta, Perfetto Federico, Mori Fabio, Parodi Oberdan, Sicari Rosa, Bombardieri Stefano, Varga Albert, Cerinic Marco Matucci, Bossone Eduardo, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation.
  
  AIM:
  The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc.
  
  METHODS:
  We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (
  RESULTS:
  Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ?3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ?50 mm Hg, but none of these parameters predict elevated peak PVR.
  
  CONCLUSIONS:
  Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.
  
  Copyright © 2013 Mosby, Inc. All rights reserved.
  
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• Influence of midwall fibrosis on diastolic dysfunction in non-ischemic cardiomyopathy.
  Int J Cardiol

  2013 Mar;163(3):342-344. doi: 10.1016/j.ijcard.2012.09.104.
  
  Moreo Antonella, Ambrosio Giuseppe, De Chiara Benedetta, Tran Tam, Raman Subha V
  
  
  
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• Plasma total cysteine and cardiovascular risk burden: action and interaction.
  ScientificWorldJournal

  2012 ;2012():303654. doi: 303654.
  
  De Chiara Benedetta, Sedda Valentina, Parolini Marina, Campolo Jonica, De Maria Renata, Caruso Raffaele, Pizzi Gianluigi, Disoteo Olga, Dellanoce Cinzia, Corno Anna Rosa, Cighetti Giuliana, Parodi Oberdan
  
  Abstract
  
  We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs), independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ? 3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027-1.110, P = 0.002). Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis.
  
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• Influence of CoreValve ReValving System implantation on mitral valve function: an echocardiographic study in selected patients.
  Catheter Cardiovasc Interv

  2011 Oct;78(4):638-44. doi: 10.1002/ccd.23045.
  
  De Chiara Benedetta, Moreo Antonella, De Marco Federico, Musca Francesco, Oreglia Jacopo, Lobiati Elisabetta, Bruschi Giuseppe, Belli Oriana, Mauri Francesco, Klugmann Silvio
  
  Abstract
  
  OBJECTIVES:
  The purpose of this study is to verify whether transcatheter aortic valve implantation (TAVI) determined changes in mitral valve (MV) function, in terms of mitral regurgitation (MR) and stenosis.
  
  BACKGROUND:
  Little data is available regarding the effects of TAVI on global MV function, often derived from analysis primarily focused on clinical and aortic related outcomes.
  
  METHODS:
  From May 2008 to March 2010, 73 patients with severe symptomatic aortic stenosis underwent TAVI with the CoreValve ReValving System. The study population consisted of 58 patients (27 males, mean age 82 ± 7 years) who underwent transthoracic echocardiography at least ?1 month after implantation (mean follow-up 7.8 ± 5.4 months).
  
  RESULTS:
  In patients with a left ventricular dysfunction (ejection fraction, EF,
  CONCLUSIONS:
  In the majority of patients no significant changes occurred in the degree of MR in native valve, but we found that if the aortic valve was deeply implanted in the left ventricle outflow tract, a worsening in MR can be observed. A mitral stenosis development must be sought in patients with heavy calcifications of the anterior leaflet.
  
  Copyright © 2011 Wiley-Liss, Inc.
  
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• Transcatheter aortic valve implantation after heart transplantation.
  Ann Thorac Surg

  2010 Nov;90(5):e66-8. doi: 10.1016/j.athoracsur.2010.08.021.
  
  Bruschi Giuseppe, De Marco Federico, Oreglia Jacopo, Colombo Paola, Moreo Antonella, De Chiara Benedetta, Paino Roberto, Frigerio Maria, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon. We report the case of a 67-year-old man who had severe symptomatic aortic stenosis develop 9 years after heart transplantation. After joint evaluation of the cardiovascular team, transcatheter aortic valve implantation was preferred due to patient medical conditions. The CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously into the femoral artery. At 4 months postoperatively, the patient is asymptomatic in New York Heart Association functional class II. This case report provides evidence that transcatheter aortic valve implantation is safe and suitable for selected patients with severe aortic stenosis and a history of heart transplantation that must improve allograft function.
  
  Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• The trans-subclavian retrograde approach for transcatheter aortic valve replacement: single-center experience.
  J Thorac Cardiovasc Surg

  2010 Oct;140(4):911-5, 915.e1-2. doi: 10.1016/j.jtcvs.2010.01.027.
  
  Bruschi Giuseppe, Fratto Pasquale, De Marco Federico, Oreglia Jacopo, Colombo Paola, Botta Luca, Cannata Aldo, Moreo Antonella, De Chiara Benedetta, Lullo Francesca, Paino Roberto, Martinelli Luigi, Klugmann Silvio
  
  Abstract
  
  OBJECTIVE:
  Aortic valve disease is the most common acquired valvular heart disease in adults. With the increasing elderly population, the proportion of patients with symptomatic aortic stenosis who are unsuitable for conventional surgery is increasing. Transcatheter aortic valve implantation has rapidly gained credibility as a valuable alternative to surgery to treat these patients; however, they often have severe iliac-femoral arteriopathy, which renders the transfemoral approach unusable. We report our experience with the trans-subclavian approach for transcatheter aortic valve implantation using the CoreValve (Medtronic CV Luxembourg S.a.r.l.) in 6 patients.
  
  METHODS:
  In May 2008 to September 2009, 6 patients (mean age of 82 ± 5 years), with symptomatic aortic stenosis and no reasonable surgical option because of excessive risk, were excluded from percutaneous femoral CoreValve implantation because of iliac-femoral arteriopathy. These patients underwent transcatheter aortic valve implantation via the axillary artery. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The CoreValve 18F delivery system was introduced via the left subclavian artery in 6 patients, 1 with a patent left internal thoracic to left anterior descending artery graft.
  
  RESULTS:
  Procedural success was obtained in all patients, and the mean aortic gradient decreased 5 mm Hg or less immediately after valve deployment. One patient required implantation of a permanent pacemaker. One patient required a subclavian covered stent implantation to treat a postimplant artery dissection associated with difficult surgical hemostasis. One patient was discharged in good condition but died of pneumonia 40 days after the procedure. All patients were asymptomatic on discharge, with good mid-term prosthesis performance.
  
  CONCLUSIONS:
  Transcatheter aortic valve implantation via a surgical subclavian approach seems safe and feasible, offering a new option to treat select, inoperable, and high-risk patients with severe aortic stenosis and peripheral vasculopathy.
  
  Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
  
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• Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive assessment by cardiac magnetic resonance and echo.
  Circ Cardiovasc Imaging

  2009 Nov;2(6):437-43. doi: 10.1161/CIRCIMAGING.108.838367.
  
  Moreo Antonella, Ambrosio Giuseppe, De Chiara Benedetta, Pu Min, Tran Tam, Mauri Francesco, Raman Subha V
  
  Abstract
  
  BACKGROUND:
  Fibrosis is a common end point of many pathological processes affecting the myocardium and may alter myocardial relaxation properties. By measuring myocardial fibrosis with cardiac magnetic resonance and diastolic function with Doppler echocardiography, we sought to define the influence of fibrosis on left ventricular diastolic function.
  
  METHODS AND RESULTS:
  Two hundred four eligible subjects from 252 consecutive subjects undergoing late postgadolinium myocardial enhancement (LGE) cardiac magnetic resonance and Doppler echocardiography were investigated. Subjects with normal diastolic function exhibited no or minimal fibrosis (median LGE score, 0; interquartile range, 0 to 0). In contrast, the majority of patients with cardiomyopathy (regardless of underlying cause) had abnormal diastolic function indices and substantial fibrosis (median LGE score, 3; interquartile range, 0 to 6.25). Prevalence of LGE positivity by diastolic filling pattern was 13% in normal, 48% in impaired relaxation, 78% in pseudonormal, and 87% in restrictive filling (P
  CONCLUSIONS:
  Severity of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction in a broad range of cardiac conditions. Noninvasive assessment of myocardial fibrosis may provide valuable insights into the pathophysiology of left ventricular diastolic function and therapeutic response.
  
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• Plasma glutathione levels are independently associated with gamma-glutamyltransferase activity in subjects with cardiovascular risk factors.
  Free Radic Res

  2008 Feb;42(2):135-41. doi: 10.1080/10715760701836821.
  
  Sedda Valentina, De Chiara Benedetta, Parolini Marina, Caruso Raffaele, Campolo Jonica, Cighetti Giuliana, De Maria Renata, Sachero Aldo, Donato Luigi, Parodi Oberdan
  
  Abstract
  
  To investigate whether GGT (gamma-glutamyltransferase) is associated to specific redox patterns. GGT, total and reduced aminothiols and malondialdehyde, were measured in 150 subjects (83 males, 48 (39-56) years), with none, one or more risk factors. By univariable analysis GGT was positively associated with age (p =0.001), male gender (p
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• Assessment of mitral prosthetic valve thrombosis by live three-dimensional echocardiography: comparison with transesophageal echocardiography.
  Heart Vessels

  2007 Jul;22(4):287-9.
  
  Moreo Antonella, Lobiati Elisabetta, De Chiara Benedetta, Mauri Francesco
  
  Abstract
  
  We report the feasibility of transthoracic live three-dimensional echocardiography in the diagnosis of a thrombus attached to the mitral bioprosthetic valve.
  
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• Functional derangement and cardiac innervation in the apical ballooning syndrome: a 123I-meta-iodobenzylguanidine scintigraphic and dobutamine stress echocardiographic study.
  J Cardiovasc Med (Hagerstown)

  2007 Mar;8(3):205-9.
  
  Moreo Antonella, De Chiara Benedetta, Possa Mario, Sara Roberto, Bossi Irene, Orrego Pedro Silva, Nicolosi Elisa, Mauri Francesco, Parodi Oberdan
  
  Abstract
  
  Several cases of transient left ventricular apical ballooning syndrome have already been described, but the pathophysiological mechanisms of this syndrome still remain unclear. We report the case of a patient evaluated in the acute phase of apical ballooning by coronary angiography and echocardiography who was submitted to I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy and dobutamine stress echocardiography one month after the discharge. MIBG scintigraphy demonstrated a decreased tracer uptake in the apical and periapical anterior regions, whilst myocardial perfusion at rest was normal. Dobutamine induced an increased left ventricular outflow tract gradient and hypokinesis in the apical and periapical segments, mimicking the findings that occurred in the acute phase, and in agreement with the location of MIBG abnormalities. After a two-month treatment with carvedilol, MIBG uptake increased in the apical and periapical anterior regions.
  
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• Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events.
  Coron Artery Dis

  2007 Mar;18(2):77-82.
  
  De Chiara Benedetta, Mafrici Antonio, Campolo Jonica, Famoso Gabriella, Sedda Valentina, Parolini Marina, Cighetti Giuliana, Lualdi Alessandro, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  To clarify whether an altered redox state persists in the subacute phase of myocardial infarction and if specific redox patterns are associated with later cardiac events.
  
  METHODS:
  Ninety-seven patients [80 men, median 63 (interquartile range, 53, 69) years] with a first acute myocardial infarction, with (53%) or without ST segment elevation, treated with successful percutaneous interventions, were tested at 5-6 days after admission for plasma alpha-tocopherol, ascorbic acid, total and reduced homocysteine, cysteine, glutathione, cysteinylglycine and blood-reduced glutathione, all assessed by high-pressure liquid chromatography. Free malondialdehyde was evaluated by gas chromatography. A subgroup of 14 patients had adjunctive blood samples within 1 h and at 72 h after angioplasty. Blood samples from 44 patients matched for age, sex, and risk factors served as controls. Patients were followed up for median 15 (interquartile range, 9, 17) months for cardiac events.
  
  RESULTS:
  All plasma-reduced aminothiols, vitamins and plasma total glutathione were significantly lower in myocardial infarction at 5-6 days than in controls. In the 14 myocardial infarction patients sampled repeatedly, plasma-reduced glutathione, cysteinylglycine, total glutathione, and alpha-tocopherol significantly decreased, whereas blood-reduced glutathione, total homocysteine, and cysteine significantly increased over time. During follow-up, 20 of 97 (21%) patients had adverse cardiac events. Multivariate analysis revealed that only plasma-reduced glutathione was independently associated with events (hazard ratio 0.42, 95% confidence interval 0.18-0.99, P=0.04).
  
  CONCLUSIONS:
  Acute myocardial infarction patients have an altered redox state at 5-6 days after successful reperfusion with respect to controls. Low plasma levels of reduced glutathione at discharge are associated with cardiac events at follow-up.
  
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• Plasma cysteine and glutathione are independent markers of postmethionine load endothelial dysfunction.
  Clin Biochem

  2007 Feb;40(3-4):188-93.
  
  Parodi Oberdan, De Chiara Benedetta, Baldassarre Damiano, Parolini Marina, Caruso Raffaele, Pustina Linda, Parodi Guido, Campolo Jonica, Sedda Valentina, Baudo Francesco, Sirtori Cesare
  
  Abstract
  
  OBJECTIVES:
  Oxidative stress caused by acute hyperhomocysteinemia impairs endothelial function in human arteries. We sought to identify markers of endothelial dysfunction during methionine-induced hyperhomocysteinemia.
  
  DESIGN AND METHODS:
  35 subjects underwent flow-mediated dilation (FMD) of the brachial artery by high-resolution ultrasonography and fasting blood samples before and 3 h postmethionine load (PML). Clinical, conventional biochemical, and redox status (plasma total and reduced homocysteine, glutathione, cysteine, cysteinylglycine, ascorbic acid, alpha-tocopherol, free malondialdehyde, blood glutathione) data were sequentially entered into an univariate and multivariate stepwise linear regression analysis to evaluate their relation with the dependent variable FMD.
  
  RESULTS:
  Median [interquartile range] FMD decreased from 4.1% [2.8-6.3] to 3.2% [0.7-4.3] PML (P=0.02). At the multivariate analysis PML total cysteine (beta=-0.008, P=0.002) and glutathione (beta=0.21, P=0.005) were the only independent variables associated with FMD after methionine, adjusted for baseline FMD.
  
  CONCLUSIONS:
  Elevated plasma total cysteine and decreased plasma total glutathione levels were associated with abnormal FMD PML. Cysteine and glutathione are stronger markers of endothelial dysfunction than clinical and all other biochemical variables explored.
  
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• [Prognostic value of serial measurements of left ventricular function and exercise performance in chronic heart failure].
  Rev Esp Cardiol

  2006 Sep;59(9):905-10.
  
  Moreo Antonella, de Chiara Benedetta, Cataldo Gabriella, Piccalò Giacomo, Lobiati Elisabetta, Parolini Marina, Frigerio Maria, Ciliberto Guglielma Rita, Mauri Francesco
  
  Abstract
  
  INTRODUCTION AND OBJECTIVES:
  The prognostic value of a single measurement of ejection fraction and peak oxygen uptake in chronic heart failure has been extensively investigated. The aim of our study was to evaluate the prognostic significance of serial changes in ejection fraction and exercise performance in moderate to severe chronic heart failure.
  
  METHODS:
  182 patients (156 men, 53 [47-58] years) underwent echocardiography and cardiopulmonary exercise testing at baseline and after 10 [8-12] months. Most patients had idiopathic dilated cardiomyopathy (69%) and all patients presented left ventricular ejection fraction
  RESULTS:
  During follow-up 18 patients (9.9%) died and 14 (7.7%) underwent heart transplantation. Baseline ejection fraction (HR, 0.94, 95% CI, 0.89-0.98 P=.006) and mitral regurgitation (HR, 4.22, 95% CI, 1.63-10.92, P=.003), and delta (second examination-baseline) ejection fraction (HR, 0.93, 95% CI, 0.88-0.98, P=.01) were the only significant variables at univariate analysis. Both ejection fraction and delta ejection fraction remained independently associated with events at multivariate analysis. The prognostic power significantly increased between a model including ejection fraction alone and another one including ejection fraction plus delta ejection fraction.
  
  CONCLUSIONS:
  In clinically stable patients with chronic heart failure, ejection fraction and its changes were independently associated with outcome; on the contrary, serial cardiopulmonary exercise testing did not provide significant prognostic value. Baseline plus changes in ejection fraction showed better prognostic performance than baseline ejection fraction alone.
  
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• Methionine challenge paradoxically induces a greater activation of the antioxidant defence in subjects with hyper- vs. normohomocysteinemia.
  Free Radic Res

  2006 Sep;40(9):929-35.
  
  Campolo Jonica, De Chiara Benedetta, Caruso Raffaele, De Maria Renata, Sedda Valentina, Dellanoce Cinzia, Parolini Marina, Cighetti Giuliana, Penco Silvana, Baudo Francesco, Parodi Oberdan
  
  Abstract
  
  To determine whether hyperhomocysteinemia induced post-methionine loading (PML) is associated with different response in the aminothiol redox state and oxidative stress vs. normohomocysteinemia, we assessed PML plasma thiols, vitamins, free malondialdehyde (MDA), and blood reduced glutathione (GSH) in 120 consecutive subjects (50 [35-56] years, 83 males), divided into two groups according to PML plasma total Hcy or = 35 microM (Group 2, n = 55). In the group as a whole, plasma reduced cysteine and cysteinylglycine, blood reduced GSH (all p for time = 0.0001) and plasma total GSH (p for time = 0.001) increased from baseline to PML. MDA values were unchanged. Group 1 and 2 differed in blood reduced GSH (p for group = 0.004, higher in Group 2), and MDA levels (p for group = 0.024, lower in Group 2). The oxidative stress induced by methionine challenge seems to be opposed by scavenger molecules activation, namely GSH, and lipid peroxidation does not increase. This mechanism paradoxically appears to be more efficient in hyperhomocysteinemic subjects.
  
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• Blood glutathione as independent marker of lipid peroxidation in heart failure.
  Int J Cardiol

  2007 Apr;117(1):45-50.
  
  Campolo Jonica, De Maria Renata, Caruso Raffaele, Accinni Roberto, Turazza Fabio, Parolini Marina, Roubina Elèna, De Chiara Benedetta, Cighetti Giuliana, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated.
  
  AIM:
  To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients.
  
  METHODS:
  Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III).
  
  RESULTS:
  MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM, p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels > or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026).
  
  CONCLUSIONS:
  Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.
  
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• An unusual cause of pulmonary edema: acute rupture of noncoronary sinus of valsalva aneurysm into the left atrium.
  J Am Soc Echocardiogr

  2006 Jul;19(7):938.e9-11.
  
  Moreo Antonella, De Chiara Benedetta, Bruschi Giuseppe, Tarelli Giuseppe, Parolini Marina, Mauri Francesco
  
  Abstract
  
  We present the case of a patient admitted to hospital with pulmonary edema and atrial fibrillation. The transthoracic echocardiogram showed noncoronary sinus of Valsalva aneurysm ruptured into the left atrium, with a turbulent flow directed toward the left atrium floor and the pulmonary vein, which explained the clinical presentation. Echocardiography played a crucial role in identification of the cause and correct therapeutic approach.
  
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• [Exercise electrocardiography for diagnostic and prognostic assessment of coronary disease. Recent advances].
  Recenti Prog Med

  2006 Mar;97(3):147-52.
  
  Bigi Riccardo, De Chiara Benedetta, Fiorentini Cesare
  
  Abstract
  
  This article focuses on recent advances on exercise electrocardiography (ECG) for the diagnostic and prognostic assessment of coronary artery disease. In particular, the pathophysiological background of comparative heart rate-adjusted ST-segment analysis during exercise and recovery phase is discussed. In addition, the results of recent studies dealing with the application of this ECG analysis modality to different clinical settings are presented.
  
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• Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia.
  J Cardiovasc Pharmacol

  2006 Apr;47(4):549-55.
  
  Caruso Raffaele, Campolo Jonica, Sedda Valentina, De Chiara Benedetta, Dellanoce Cinzia, Baudo Francesco, Tonini Annamaria, Parolini Marina, Cighetti Giuliana, Parodi Oberdan
  
  Abstract
  
  The endothelial dysfunction induced by hyperhomocysteinemia can be reversed by 5-methyltetrahydrofolate (5-MTHF) via homocysteine (Hcy) lowering. An additive antioxidant action of 5-MTHF has been suggested to ameliorate endothelial dysfunction through increased nitric oxide production and superoxide radical scavenging, independent of Hcy lowering. The aim of the study was to assess whether 5-MTHF affects the redox state in hyperhomocysteinemia. We examined the effect of 3 months of oral 5-MTHF treatment (15 mg/day) on the redox pattern in 48 hyperhomocysteinemic subjects compared to 24 untreated hyperhomocysteinemic subjects. By analysis of variance with repeated measures in the 72 subjects, 5-MTHF markedly decreased plasma total Hcy (p-tHcy; P = 0.0001) and blood-total glutathione (GSH; b-tGSH; P = 0.002). By multivariate linear regression in the treated subjects, p-tHcy changes from baseline to 3 months (adjusted by baseline p-tHcy levels) correlated only with changes in reduced cysteinylglycine (P = 0.001). The effects of treatment on Hcy lowering and GSH metabolism were greater in medium than in moderate hyperhomocysteinemia. In conclusion, high-dose 5-MTHF treatment for 3 months ensures marked Hcy lowering to normal values even in subjects with high Hcy levels, and should be the treatment of choice in medium hyperhomocysteinemia. Furthermore, 5-MTHF shows a favorable interaction with GSH metabolism.
  
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• [Use of imaging in the evaluation of heart transplant recipients].
  Ital Heart J Suppl

  2005 Sep;6(9):561-8.
  
  De Chiara Benedetta, Roubina Elèna, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  Common complications after heart transplantation include acute rejection and coronary allograft vasculopathy. In order to detect the presence of rejection, tissue Doppler imaging echocardiography provides high accuracy and allows to optimize the timing of endomyocardial biopsies, which remain the cornerstone in rejection diagnosis. Coronary allograft vasculopathy is often a diffuse disease so that it is difficult to recognize by imaging modalities, such as myocardial perfusion scintigraphy, which are based on intra-patient comparison of different areas. Quantitative assessment of the myocardial blood flow by positron emission tomography overcomes this issue. Dobutamine stress echocardiography provides accurate diagnosis as well as useful prognostic information. Nevertheless, intracoronary ultrasound is nowadays considered the gold standard for vasculopathy assessment, since it is able to detect a minimum intimal thickening which represents the early feature of disease. Magnetic resonance represents the most attractive approach, though it has not yet gained widespread clinical use.
  
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• Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients.
  Clin Transplant

  2005 Jun;19(3):367-71.
  
  De Chiara Benedetta, Bigi Riccardo, Campolo Jonica, Parolini Marina, Turazza Fabio, Masciocco Gabriella, Frigerio Maria, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV.
  
  METHODS:
  Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis.
  
  RESULTS:
  CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008).
  
  CONCLUSIONS:
  In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.
  
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• Early detection of cardiac dysfunction in thalassemic patients by radionuclide angiography and heart rate variability analysis.
  Eur J Haematol

  2005 Jun;74(6):517-22.
  
  De Chiara Benedetta, Crivellaro Wilma, Sara Roberto, Ruffini Livia, Parolini Marina, Fesslovà Vlasta, Carnelli Vittorio, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Cardiac dysfunction remains the major cause of death in beta-thalassemia. Aim of this study was to assess early myocardial damage in thalassemic patients with no symptoms or echocardiographic evidence of dysfunction at routine monitoring.
  
  METHODS:
  Twenty patients (seven females; median 25 yr [first quartile 22,third quartile 28]) with beta-thalassemia underwent radionuclide angiography (RNA) at rest and during low-dose dobutamine infusion (5-10 gamma/kg/min). Right and left ventricular ejection fractions (EF) were determined by first-pass method and gated equilibrium acquisition, respectively. Twenty-four-hour Holter monitoring with time-domain heart rate variability (HRV) assessment and echocardiographic follow-up (21 months [5,27]) were performed.
  
  RESULTS:
  Eleven patients showed regional wall motion abnormalities at RNA; left ventricular EF, HR and diastolic measurements significantly increased after dobutamine infusion. Patients with abnormal RNA right ventricular EF (n = 8,
  CONCLUSIONS:
  Right ventricular dysfunction and abnormal HRV may represent the early features of cardiac disease in thalassemic patients with no evidence of ventricular dysfunction at routine evaluation.
  
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• Prognostic value of noninvasive stressing modalities in patients with chest pain and normal coronary angiogram.
  Herz

  2005 Feb;30(1):61-6.
  
  Bigi Riccardo, De Chiara Benedetta
  
  Abstract
  
  Risk stratification of patients with recurrent chest pain and normal coronary angiogram is a relevant but still definitely unsolved clinical problem. In this article the relative value of mostly used noninvasive stress testing modalities is reviewed. In addition, future perspectives derived from alternative pathophysiological insights and new diagnostic approaches are briefly discussed.
  
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• Exercise versus recovery electrocardiography for predicting outcome in hypertensive patients with chest pain.
  J Hypertens

  2004 Nov;22(11):2193-9.
  
  Bigi Riccardo, Cortigiani Lauro, Gregori Dario, De Chiara Benedetta, Parodi Oberdan, Fiorentini Cesare
  
  Abstract
  
  BACKGROUND:
  Exercise electrocardiography has limited prognostic accuracy in hypertensives because of unsatisfactory specificity. We prospectively used comparative stress-recovery heart rate-adjusted ST (ST/HR) analysis to predict mortality in a consecutive population of hypertensives with chest pain.
  
  METHODS:
  The stress-recovery index (SRI), defined as the difference between ST/HR areas during exercise and recovery, was derived in 460 hypertensive with known (n=360, 78%) or suspected (n=100, 22%) coronary artery disease. To assess whether it added prognostic information to routinely obtained information, clinical data, the resting ejection fraction, and exercise testing data were entered into a sequential Cox's model; the SRI was entered last. Model validation was performed by bootstrap adjusted by the degree of optimism in estimates. Survival analysis was performed using the product-limit Kaplan-Meier method.
  
  RESULTS:
  During a median follow-up of 28 months (interquartile range, 13-44 months), 32 (7%) patients died, 23 (5%) suffered from acute myocardial infarction and 60 (13%) underwent late (> 3 months) revascularization. Male gender (hazard ratio, 1.53; 95% confidence interval, 1.01-2.34), peak double product (hazard ratio, 0.70; 95% confidence interval, 0.54-0.90) and the SRI (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81 for interquartile difference) were independent predictors of outcome. The SRI increased the prognostic power of the model on top of clinical and exercise testing variables (concordance index, + 10%; discrimination index, + 32%) and showed the widest area under the ROC curve to predict outcome as compared with exercise-only ST analysis and the ST/HR index. Moreover, it provided a significant discrimination of survival.
  
  CONCLUSIONS:
  The SRI predicts all-cause mortality in hypertensive patients with chest pain and provides additional prognostic information over clinical and standard exercise testing data.
  
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• Effect of pharmacological wash-out in patients undergoing exercise testing after acute myocardial infarction.
  Int J Cardiol

  2004 Nov;97(2):277-81.
  
  Bigi Riccardo, Verzoni Alessandro, Cortigiani Lauro, De Chiara Benedetta, Desideri Alessandro, Fiorentini Cesare
  
  Abstract
  
  STUDY OBJECTIVES:
  Pharmacological therapy can reduce diagnostic and prognostic accuracy of exercise stress testing. However, the risk of withdrawing drugs early after myocardial infarction (MI) has not been established. We assessed safety and clinical implications of drug withdrawal in patients undergoing stress testing after uncomplicated MI.
  
  METHODS:
  A total of 362 MI patients underwent ECG Holter recording before and after withdrawing beta-blockers, calcium-antagonists and nitrates. QRS (QRS/h) and ventricular premature beats (VPB/h) count per hour, repetitive ventricular arrhythmias, ST segment changes and patient complaints were evaluated for reproducibility using kappa statistics and Bland-Altman method.
  
  RESULTS:
  No major complications occurred. Forty-three patients complained of >1 symptom on and 37 off therapy. QRS/h and VPB/h count were significantly (p
  CONCLUSIONS:
  The withdrawal of therapy is well tolerated soon after uncomplicated MI; however, a generic but not individual risk of ventricular arrhythmias and/or transient myocardial ischemia has to be taken into account.
  
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• Exercise versus recovery electrocardiography in predicting mortality in patients with uncomplicated myocardial infarction.
  Eur Heart J

  2004 Apr;25(7):558-64.
  
  Bigi Riccardo, Cortigiani Lauro, Gregori Dario, De Chiara Benedetta, Fiorentini Cesare
  
  Abstract
  
  BACKGROUND:
  Exercise testing after acute myocardial infarction has limited prognostic accuracy. We prospectively used stress-recovery, heart rate-adjusted, ST-segment analysis to predict cardiac death in this clinical setting.
  
  METHODS:
  The stress-recovery index, defined as the difference in absolute values of the areas designated by ST depression in the heart-rate domain during exercise and recovery, was derived in 708 survivors of a first myocardial infarction. To assess whether it contributed additional prognostic information to routinely obtained information, clinical data, resting ejection fraction, and exercise testing data were entered into a sequential Cox model; the stress-recovery index was entered last. Model validation was performed by bootstrapping adjusted for the degree of optimism in estimates. Survival curves were set up using Kaplan-Meier analysis and compared by the log-rank test.
  
  RESULTS:
  Hypertension (OR 1.3, 95%CI 0.9-4.6), exercise capacity (OR 0.6, 95%CI 0.3-1.1 for the interquartile difference in kilopounds per minute), and the stress-recovery index (OR 0.7, 95%CI 0.5-0.9 for the interquartile difference) were independent predictors of cardiac death at a median follow-up of 32 months. However, the stress-recovery index enhanced the prognostic power of the model on top of clinical and exercise testing variables in all diagnostic subgroups according to ST-segment analysis and significantly discriminated survival. A simple nomogram was generated from the fitted Cox model to estimate risk in individual patients.
  
  CONCLUSIONS:
  Stress-recovery, heart rate-adjusted, ST-segment analysis predicts cardiac death after acute myocardial infarction and provides additional prognostic information over clinical and exercise testing data.
  
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• Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.
  Am J Cardiol

  2003 Oct;92(8):1001-4.
  
  De Chiara Benedetta, Bigi Riccardo, Devoto Emmanuela, Cavenaghi Giorgio, Turazza Fabio, Sara Roberto, Colombo Tiziano, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.
  
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