Dott.ssa Sicari Rosa

Pubblicazioni su PubMed

• Cancer Risk in Patients With Congenital Heart Disease Exposed to Radiation From Cardiac Procedures.
  J Am Coll Cardiol

  2023 Mar;81(11):1133-1134. doi: 10.1016/j.jacc.2022.12.028.
  
  Borghini Andrea, Campolo Jonica, Annoni Giuseppe, Giuli Valentina, Sicari Rosa, Peretti Alessio, Mercuri Antonella, Picano Eugenio, Andreassi Maria Grazia
  
  
  
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• Of high water, stress echo, and diastole.
  Eur Heart J Cardiovasc Imaging

  2023 Feb;():. doi: jead029.
  
  Sicari Rosa
  
  
  
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• Prognostic Role of Sonographic Decongestion in Patients with Acute Heart Failure with Reduced and Preserved Ejection Fraction: A Multicentre Study.
  J Clin Med

  2023 Jan;12(3):. doi: 773.
  
  Pugliese Nicola R, Mazzola Matteo, Bandini Giulia, Barbieri Greta, Spinelli Stefano, De Biase Nicolò, Masi Stefano, Moggi-Pignone Alberto, Ghiadoni Lorenzo, Taddei Stefano, Sicari Rosa, Pang Peter S, De Carlo Marco, Gargani Luna
  
  Abstract
  
  BACKGROUND:
  We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF).
  
  METHODS:
  In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings.
  
  RESULTS:
  We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70-84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80,
  CONCLUSIONS:
  The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.
  
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• Non-Invasive Imaging in Coronary Syndromes: Recommendations of The European Association of Cardiovascular Imaging and the American Society of Echocardiography, in Collaboration with The American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.
  J Cardiovasc Comput Tomogr

  2022 ;16(4):362-383. doi: 10.1016/j.jcct.2022.05.006.
  
  Edvardsen Thor, Asch Federico M, Davidson Brian, Delgado Victoria, DeMaria Anthony, Dilsizian Vasken, Gaemperli Oliver, Garcia Mario J, Kamp Otto, Lee Daniel C, Neglia Danilo, Neskovic Aleksandar N, Pellikka Patricia A, Plein Sven, Sechtem Udo, Shea Elaine, Sicari Rosa, Villines Todd C, Lindner Jonathan R, Popescu Bogdan A
  
  
  
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• Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome.
  Int J Cardiol

  2022 Aug;361():14-17. doi: 10.1016/j.ijcard.2022.05.027.
  
  Myhre Peder L, Røsjø Helge, Sarvari Sebastian I, Ukkonen Heikki, Rademakers Frank, Engvall Jan E, Hagve Tor-Arne, Nagel Eike, Sicari Rosa, Zamorano Jose L, Monaghan Mark, D'hooge Jan, Edvardsen Thor, Omland Torbjørn
  
  Abstract
  
  BACKGROUND:
  Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear.
  
  METHODS:
  Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples.
  
  RESULTS:
  We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p 90%.
  
  CONCLUSION:
  cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.
  
  Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
  
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• Diagnosing HCM severity: The role of microvascular impairment.
  Int J Cardiol

  2022 Aug;360():44. doi: 10.1016/j.ijcard.2022.05.017.
  
  Sicari Rosa
  
  
  
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• Non-Invasive Imaging in Coronary Syndromes: Recommendations of The European Association of Cardiovascular Imaging and the American Society of Echocardiography, in Collaboration with The American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.
  J Am Soc Echocardiogr

  2022 Apr;35(4):329-354. doi: 10.1016/j.echo.2021.12.012.
  
  Edvardsen Thor, Asch Federico M, Davidson Brian, Delgado Victoria, DeMaria Anthony, Dilsizian Vasken, Gaemperli Oliver, Garcia Mario J, Kamp Otto, Lee Daniel C, Neglia Danilo, Neskovic Aleksandar N, Pellikka Patricia A, Plein Sven, Sechtem Udo, Shea Elaine, Sicari Rosa, Villines Todd C, Lindner Jonathan R, Popescu Bogdan A
  
  
  
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• Phenotyping heart failure with preserved ejection fraction with exercise stress echocardiography.
  Eur Heart J Cardiovasc Imaging

  2022 Jul;23(8):1053-1054. doi: 10.1093/ehjci/jeac053.
  
  Sicari Rosa
  
  
  
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• Non-invasive imaging in coronary syndromes: recommendations of the European Association of Cardiovascular Imaging and the American Society of Echocardiography, in collaboration with the American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance.
  Eur Heart J Cardiovasc Imaging

  2022 Jan;23(2):e6-e33. doi: 10.1093/ehjci/jeab244.
  
  Edvardsen Thor, Asch Federico M, Davidson Brian, Delgado Victoria, DeMaria Anthony, Dilsizian Vasken, Gaemperli Oliver, Garcia Mario J, Kamp Otto, Lee Daniel C, Neglia Danilo, Neskovic Aleksandar N, Pellikka Patricia A, Plein Sven, Sechtem Udo, Shea Elaine, Sicari Rosa, Villines Todd C, Lindner Jonathan R, Popescu Bogdan A
  
  
  
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• The evolving role of cardiac imaging in patients with myocardial infarction and non-obstructive coronary arteries.
  Prog Cardiovasc Dis

  2021 ;68():78-87. doi: 10.1016/j.pcad.2021.08.004.
  
  Montone Rocco A, Jang Ik-Kyung, Beltrame John F, Sicari Rosa, Meucci Maria Chiara, Bode Michael, Gaibazzi Nicola, Niccoli Giampaolo, Bucciarelli-Ducci Chiara, Crea Filippo
  
  Abstract
  
  Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%-8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.
  
  Copyright © 2021 Elsevier Inc. All rights reserved.
  
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• A randomized multicenter trial on a lung ultrasound-guided treatment strategy in patients on chronic hemodialysis with high cardiovascular risk.
  Kidney Int

  2021 Dec;100(6):1325-1333. doi: 10.1016/j.kint.2021.07.024.
  
  Zoccali Carmine, Torino Claudia, Mallamaci Francesca, Sarafidis Pantelis, Papagianni Aikaterini, Ekart Robert, Hojs Radovan, Klinger Marian, Letachowicz Krzysztof, Fliser Danilo, Seiler-Mußler Sarah, Lizzi Fabio, Wiecek Andrzej, Miskiewicz Agata, Siamopoulos Kostas, Balafa Olga, Slotki Itzchak, Shavit Linda, Stavroulopoulos Aristeidis, Covic Adrian, Siriopol Dimitrie, Massy Ziad A, Seidowsky Alexandre, Battaglia Yuri, Martinez-Castelao Alberto, Polo-Torcal Carolina, Coudert-Krier Marie-Jeanne, Rossignol Patrick, Fiaccadori Enrico, Regolisti Giuseppe, Hannedouche Thierry, Bachelet Thomas, Jager Kitty J, Dekker Friedo W, Tripepi Rocco, Tripepi Giovanni, Gargani Luna, Sicari Rosa, Picano Eugenio, London Gérard Michel
  
  Abstract
  
  Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.
  
  Copyright © 2021. Published by Elsevier Inc.
  
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• Exercise and coronary flow velocity reserve: these are words that go together well.
  Acta Cardiol

  2022 Aug;77(6):564. doi: 10.1080/00015385.2021.1963097.
  
  Sicari Rosa
  
  
  
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• Training, training and more training.
  Int J Cardiovasc Imaging

  2021 Jul;37(7):2169. doi: 10.1007/s10554-021-02264-6.
  
  Sicari Rosa
  
  
  
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• Prognostic value of lung ultrasound in patients hospitalized for heart disease irrespective of symptoms and ejection fraction.
  ESC Heart Fail

  2021 Aug;8(4):2660-2669. doi: 10.1002/ehf2.13206.
  
  Gargani Luna, Pugliese Nicola Riccardo, Frassi Francesca, Frumento Paolo, Poggianti Elisa, Mazzola Matteo, De Biase Nicolò, Landi Patrizia, Masi Stefano, Taddei Stefano, Pang Peter S, Sicari Rosa
  
  Abstract
  
  AIMS:
  Lung ultrasound B-lines are the sonographic sign of pulmonary congestion and can be used in the differential diagnosis of dyspnoea to rule in or rule out acute heart failure (AHF). Our aim was to assess the prognostic value of B-lines, integrated with echocardiography, in patients admitted to a cardiology department, independently of the initial clinical presentation, thus in patients with and without AHF, and in AHF with reduced and preserved ejection fraction (HFrEF and HFpEF).
  
  METHODS AND RESULTS:
  We enrolled consecutive patients admitted for various cardiac conditions. Patients were classified into three groups: (i) acute HFrEF; (ii) acute HFpEF; and (iii) non-AHF. All patients underwent an echocardiogram coupled with lung ultrasound at admission, according to standardized protocols. We followed up 1021 consecutive inpatients (69 ± 12 years) for a median of 14.4 months (interquartile range 4.6-24.3) for death and rehospitalization for AHF. During the follow-up, 126 events occurred. Admission B-lines > 30, ejection fraction  2.8 m/s, and tricuspid annular plane systolic excursion  30 had a strong predictive value in HFpEF and non-AHF, but not in HFrEF.
  
  CONCLUSIONS:
  Ultrasound B-lines can detect subclinical pulmonary interstitial oedema in patients thought to be free of congestion and provide useful information not only for the diagnosis but also for the prognosis in different cardiac conditions. Their added prognostic value among standard echocardiographic parameters is more robust in patients with HFpEF compared with HFrEF.
  
  © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
  
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• The curious incident of CFVR in clinical practice.
  Eur Heart J

  2021 Jan;42(3):240-242. doi: 10.1093/eurheartj/ehaa1006.
  
  Sicari Rosa
  
  
  
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• Inflammation is an amplifier of lung congestion by high lv filling pressure in hemodialysis patients: a longitudinal study.
  J Nephrol

  2020 Jun;33(3):583-590. doi: 10.1007/s40620-019-00696-x.
  
  Torino Claudia, Gargani Luna, Sicari Rosa, Letachowicz Krzysztof, Ekart Robert, Fliser Danilo, Covic Adrian, Siamopoulos Kostas, Stavroulopoulos Aristeidis, Massy Ziad A, Fiaccadori Enrico, Regolisti Giuseppe, Bachelet Thomas, Slotki Itzchak, Martinez-Castelao Alberto, Coudert-Krier Marie-Jeanne, Rossignol Patrick, Hannedouche Thierry, Wiecek Andrzej, Sarafidis Pantelis, Battaglia Yuri, Prohi? Nejra, Klinger Marian, Hojs Radovan, Seiler-Mußler Sarah, Lizzi Fabio, Siriopol Dimitrie, Balafa Olga, Shavit Linda, Loutradis Charalampos, Seidowsky Alexandre, Tripepi Rocco, Mallamaci Francesca, Tripepi Giovanni, Picano Eugenio, London Gérard Michel, Zoccali Carmine
  
  Abstract
  
  INTRODUCTION:
  Since inflammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifier of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients.
  
  OBJECTIVE AND METHODS:
  We investigated the effect modification by systemic inflammation (serum CRP) on the relationship between a surrogate of the filling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantified by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model.
  
  RESULTS:
  At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r?=?0.23, P?0.001) and serum CRP was a robust modifier of this relationship (P?0.001). Similarly, in fully adjusted longitudinal analyses US-B lines associated with simultaneous estimates of LAVI (P?=?0.002) and again CRP was a strong modifier of this relationship in adjusted analyses (P???0.01). Overall, at comparable LAVI levels, lung congestion was more pronounced in inflamed than in non-inflamed patients.
  
  CONCLUSION:
  In ESKD systemic inflammation is a modifier of the relationship between LAVI, an integrate measure of LV filling pressure, and lung water. For any given pressure, lung water is increased with higher CRP levels, likely reflecting a higher permeability of the alveolar-capillary barrier.
  
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• Anatomical and functional coronary imaging to predict long-term outcome in patients with suspected coronary artery disease: the EVINCI-outcome study.
  Eur Heart J Cardiovasc Imaging

  2020 Oct;21(11):1273-1282. doi: 10.1093/ehjci/jez248.
  
  Neglia Danilo, Liga Riccardo, Caselli Chiara, Carpeggiani Clara, Lorenzoni Valentina, Sicari Rosa, Lombardi Massimo, Gaemperli Oliver, Kaufmann Philipp A, Scholte Arthur J H A, Underwood S Richard, Knuuti Juhani,
  
  Abstract
  
  AIMS:
  To investigate the prognostic relevance of coronary anatomy, coronary function, and early revascularization in patients with stable coronary artery disease (CAD).
  
  METHODS AND RESULTS:
  From March 2009 to June 2012, 430 patients with suspected CAD (61?±?9?years, 62% men) underwent coronary anatomical imaging by computed tomography coronary angiography (CTCA) and coronary functional imaging followed by invasive coronary angiography (ICA) if at least one non-invasive test was abnormal. Obstructive CAD was documented by ICA in 119 patients and 90 were revascularized within 90?days of enrolment. Core laboratory analysis showed that 134 patients had obstructive CAD by CTCA (>50% stenosis in major coronary vessels) and 79 significant ischaemia by functional imaging [>10% left ventricular (LV) myocardium]. Over mean follow-up of 4.4 years, major adverse events (AEs) (all-cause death, non-fatal myocardial infarction, or hospital admission for unstable angina or heart failure) or AEs plus late revascularization (LR) occurred in 40 (9.3%) and 58 (13.5%) patients, respectively. Obstructive CAD at CTCA was the only independent imaging predictor of AEs [hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.10-9.30; P?=?0.033] and AEs plus LR (HR 4.3, 95% CI 1.56-11.81; P?=?0.005). Patients with CAD in whom early revascularization was performed in the presence of ischaemia and deferred in its absence had fewer AEs, similar to patients without CAD (HR 2.0, 95% CI 0.71-5.51; P?=?0.195).
  
  CONCLUSION:
  Obstructive CAD imaged by CTCA is an independent predictor of clinical outcome. Early management of CAD targeted to the combined anatomical and functional disease phenotype improves clinical outcome.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
  
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• Usefulness of dual imaging stress echocardiography for the diagnosis of coronary allograft vasculopathy in heart transplant recipients.
  Int J Cardiol

  2019 Dec;296():109-112. doi: 10.1016/j.ijcard.2019.06.081.
  
  Pichel Irene Álvarez, Fernández Cimadevilla Oliva C, de la Hera Galarza Jesús María, Pasanisi Emilio, Ruiz José Manuel García, Molina Beatriz Díaz, Rodriguez José Luis Lambert, Sicari Rosa, Fernández María Martín
  
  Abstract
  
  BACKGROUND:
  Coronary allograft vasculopathy (CAV) is the main factor limiting long-term survival after cardiac transplantation. Dual imaging stress echocardiography with wall motion and Doppler-derived coronary flow reserve (CRF) of the left anterior descending artery (LAD) is a state-of-the-art methodology during dipyridamole stress echocardiography (DiSE). This study involving 74 heart transplanted patients has the purpose to assess the diagnostic value of dipyridamole stress echocardiography with evaluation of wall motion (WM) and Doppler-derived coronary flow reserve for the diagnosis of coronary allograft vasculopathy.
  
  METHODS AND RESULTS:
  All patients underwent DiSE and coronary angiography. Moderate-severe CAV was defined according to International Society of Heart and Lung Transplant (ISHLT) recommended nomenclature for CAV, and CFR?2 was considered to be impaired. Moderate-severe CAV was present in 11 patients. WM analysis revealed four patients (5%) with rest WM abnormalities. CFR analysis revealed that 40 (54%) individuals had an abnormal result. The combined evaluation of WM analysis and CFR resulted in a sensitivity of 72.7% (95% CI: 39.3 to 92.6%), a specificity of 49.2% (95% CI: 36.5 to 61.9%), a positive predictive value of 20% (95% CI: 9.6 to 36.1%), and negative predictive value of 91.1% (95% CI: 75.1 to 97.6%) for the diagnosis of CAV.
  
  CONCLUSIONS:
  Our results support the inclusion of DiSE performance in Heart transplant follow up protocol. The addition of CFR evaluation offers valuable information to the angiography findings in the detection of CAV and could be helpful in selected patients to adjust the time and indications of coronary angiography.
  
  Copyright © 2019 Elsevier B.V. All rights reserved.
  
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• The Prognostic Value of Coronary Flow Velocity Reserve in Two Coronary Arteries During Vasodilator Stress Echocardiography.
  J Am Soc Echocardiogr

  2019 Jan;32(1):81-91. doi: 10.1016/j.echo.2018.09.002.
  
  Cortigiani Lauro, Rigo Fausto, Bovenzi Francesco, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Vasodilator stress echocardiography (SE) allows combined evaluation of regional wall motion and Doppler coronary flow velocity reserve (CFVR) of both the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). The aim of this study was to prospectively assess the prognostic correlates of LAD and RCA CFVR on SE.
  
  METHODS:
  A total of 1,365 patients with known or suspected coronary artery disease underwent dipyridamole SE with combined evaluation of CFVR in both the LAD and the RCA.
  
  RESULTS:
  Ischemia was present on SE in 263 patients (19%). CFVR was abnormal (?2.0) in 545 patients (40%): 172 in the LAD only, 149 in the RCA only, and 224 in both the LAD and the RCA. During a median follow-up period of 20 months, 44 deaths and 98 myocardial infarctions occurred. In the overall population, LAD CFVR ? 2.0 (hazard ratio [HR], 3.93) and inducible ischemia (HR, 2.74) were multivariate prognostic predictors. In the subset with ischemia on SE, CFVR did not add to peak wall motion score index (HR, 2.23). In patients without ischemia on SE, age (HR, 1.04), anti-ischemic therapy at the time of testing (HR, 1.6) and LAD CFVR ? 2.0 (HR, 10.8) were independent prognostic indicators. In patients without ischemia on SE and LAD CFVR >2.0, the 4-year event rate was 4% in those with RCA CFVR > 2.0 and 18% in those with RCA CFVR ? 2.0 (P 
  CONCLUSIONS:
  Ischemia on SE with high peak wall motion score index identifies a high-risk subset regardless of the underlying CFVR response. Absence of ischemia on SE is associated with intermediate risk, and LAD CFVR is essential to identify a truly low-risk subset. RCA CFVR is less useful than LAD CFVR but may have a role for further risk stratification in patients without ischemia and normal LAD CFVR.
  
  Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
  
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• The use of handheld ultrasound devices: a position statement of the European Association of Cardiovascular Imaging (2018 update).
  Eur Heart J Cardiovasc Imaging

  2019 Mar;20(3):245-252. doi: 10.1093/ehjci/jey145.
  
  Cardim Nuno, Dalen Havard, Voigt Jens-Uwe, Ionescu Adrian, Price Susanna, Neskovic Alexsandar N, Edvardsen Thor, Galderisi Maurizio, Sicari Rosa, Donal Erwan, Stefanidis Alexandros, Delgado Victoria, Zamorano Jose, Popescu Bogdan A
  
  Abstract
  
  Recent technological advances in echocardiography, with progressive miniaturization of ultrasound machines, have led to the development of handheld ultrasound devices (HUD). These devices, no larger than some mobile phones, can be used to perform partial, focused exams as an extension to the physical examination. The European Association of Cardiovascular Imaging (EACVI) acknowledges that the dissemination of appropriate HUD use is inevitable and desirable, because of its potential impact on patient management. However, as a scientific society of cardiac imaging, our role is to provide guidance in order to optimize patient benefit and minimize drawbacks from inappropriate use of this technology. This document provides updated recommendations for the use of HUD, including nomenclature, appropriateness, indications, operators, clinical environments, data management and storage, educational needs, and training of potential users. It also addresses gaps in evidence, controversial issues, and future technological developments.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
  
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• Prognostic value of dual imaging stress echocardiography following coronary bypass surgery.
  Int J Cardiol

  2019 Feb;277():266-271. doi: 10.1016/j.ijcard.2018.09.105.
  
  Cortigiani Lauro, Ciampi Quirino, Rigo Fausto, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  AIMS:
  To assess the prognostic value of dual imaging stress echocardiography after coronary artery bypass grafting (CABG). Dual imaging stress echocardiography, combining the evaluation of regional wall motion and Doppler echocardiographic derived coronary flow velocity reserve (CFVR) of the left anterior descending artery (LAD), is the state-of-the-art methodology during vasodilatory stress.
  
  METHODS AND RESULTS:
  In a prospective, multicenter, observational study, 349 patients (270 men; 69?±?9?years; 262 symptomatic) with history of CABG underwent high-dose dipyridamole (0.84?mg/kg over 6?min) stress echocardiography with CFVR evaluation of LAD by Doppler. The composite endpoint of death and myocardial infarction was considered in the survival analysis. Positivity rate with either criteria was 13% in the 262 symptomatic patients with appropriate and 6% in the 87 asymptomatic patients with maybe/rarely appropriate indications on the basis of 2014 American College of Cardiology Foundation guidelines. During a median follow-up of 22?months (1st quartile 8, 3rd quartile 44), there were 56 (16%) events: 21 deaths, and 35 nonfatal myocardial infarctions. At Cox analysis, ischemia at stress echo (HR 4.80, 95% CI 2.69-8.55; p?0.0001), and CFVR of LAD ?2 (HR 2.28, 95% CI 1.32-3.95; p?=?0.003) were multivariable prognostic predictors. Considering the group with no ischemia, patients with CFVR ?2 showed 2.5 fold higher yearly hard events as compared to those with CFVR >2 (7.5 vs 2.9%; p?=?0.002).
  
  CONCLUSIONS:
  Dual imaging stress echocardiography provides useful prognostic information following CABG. Inducible ischemia and abnormal CFVR are strong and independent prognostic indicators in patients with appropriate and rarely/maybe appropriate indications.
  
  Copyright © 2018. Published by Elsevier B.V.
  
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• Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.
  Clin Chem

  2018 Sep;64(9):1370-1379. doi: 10.1373/clinchem.2018.288894.
  
  Myhre Peder L, Omland Torbjørn, Sarvari Sebastian I, Ukkonen Heikki, Rademakers Frank, Engvall Jan E, Hagve Tor-Arne, Nagel Eike, Sicari Rosa, Zamorano Jose L, Monaghan Mark, D'hooge Jan, Edvardsen Thor, Røsjø Helge,
  
  Abstract
  
  BACKGROUND:
  Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known.
  
  METHODS:
  We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography.
  
  RESULTS:
  Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g;
  CONCLUSIONS:
  hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.
  
  © 2018 American Association for Clinical Chemistry.
  
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• Vascular Function Is Improved After an Environmental Enrichment Program: The Train the Brain-Mind the Vessel Study.
  Hypertension

  2018 Jun;71(6):1218-1225. doi: 10.1161/HYPERTENSIONAHA.117.10066.
  
  Bruno Rosa Maria, Stea Francesco, Sicari Rosa, Ghiadoni Lorenzo, Taddei Stefano, Ungar Andrea, Bonuccelli Ubaldo, Tognoni Gloria, Cintoli Simona, Del Turco Serena, Sbrana Silverio, Gargani Luna, D'Angelo Gennaro, Pratali Lorenza, Berardi Nicoletta, Maffei Lamberto, Picano Eugenio,
  
  Abstract
  
  UNLABELLED:
  Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65-89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10; =0.009); only the latter remained significant after adjustment for confounders (=0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; =0.006; =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa; =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 cells, and preserved carotid distensibility.
  
  CLINICAL TRIAL REGISTRATION:
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178.
  
  © 2018 American Heart Association, Inc.
  
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• Stress echocardiography: time for a reassessment?
  Int J Cardiol

  2018 May;259():47-48. doi: 10.1016/j.ijcard.2018.02.022.
  
  Sicari Rosa
  
  
  
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• Right atrial function: A blind spot in a blind spot.
  Int J Cardiol

  2018 Mar;255():212. doi: 10.1016/j.ijcard.2017.12.077.
  
  Sicari Rosa
  
  
  
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• Stress Echocardiography Positivity Predicts Cancer Death.
  J Am Heart Assoc

  2017 Dec;6(12):. doi: e007104.
  
  Carpeggiani Clara, Landi Patrizia, Michelassi Claudio, Andreassi Maria Grazia, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Stress echocardiography (SE) predicts cardiac death, but an increasing share of cardiac patients eventually die of cancer. The aim of the study was to assess whether SE positivity predicts cancer death.
  
  METHODS AND RESULTS:
  In a retrospective analysis of prospectively acquired single-center, observational data, we evaluated 4673 consecutive patients who underwent SE from 1983 to 2009. All patients were cancer-free at index SE and were followed up for a median of 131 months (interquartile range 134). We separately analyzed predetermined end points: cardiovascular, cancer, and noncardiovascular, noncancer death, with and without competing risk. SE was positive in 1757 and negative in 2916 patients; 869 cardiovascular, 418 cancer, and 625 noncardiovascular, noncancer deaths were registered. The 25-year mortality was higher in SE-positive than in SE-negative patients, considering cardiovascular (40% versus 31%;
  CONCLUSIONS:
  SE results predict cardiovascular and cancer mortality. SE may act as a proxy of the shared risk factor milieu for cancer or cardiovascular death.
  
  © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
  
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• Maternal Obesity and Cardiac Development in the Offspring: Study in Human Neonates and Minipigs.
  JACC Cardiovasc Imaging

  2018 Dec;11(12):1750-1755. doi: 10.1016/j.jcmg.2017.08.024.
  
  Guzzardi Maria Angela, Liistro Tiziana, Gargani Luna, Ait Ali Lamia, D'Angelo Gennaro, Rocchiccioli Silvia, La Rosa Federica, Kemeny Alessandra, Sanguinetti Elena, Ucciferri Nadia, De Simone Mariarosaria, Bartoli Antonietta, Festa Pierluigi, Salvadori Piero A, Burchielli Silvia, Sicari Rosa, Iozzo Patricia
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term).
  
  BACKGROUND:
  The epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality.
  
  METHODS:
  Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood.
  
  RESULTS:
  In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p 
  CONCLUSIONS:
  Neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function.
  
  Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Simple six-item clinical score improves risk prediction capability of stress echocardiography.
  Heart

  2018 May;104(9):760-766. doi: 10.1136/heartjnl-2017-312122.
  
  Cortigiani Lauro, Carpeggiani Clara, Sicari Rosa, Michelassi Claudio, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  OBJECTIVES:
  To assess the value of a simple score integrating non-ischaemia-related variables in expanding the wall motion abnormalities risk power during stress echocardiography (SE).
  
  METHODS:
  Study includes 14?279 patients who underwent SE for evaluation of coronary artery disease. All-cause death was the end point. Patients were randomly divided into the modelling and validation group of equal size. In the modelling group, multivariate analysis was conducted using clinical, rest and SE data, and a score was obtained from the number of non-ischaemia-related independent prognostic predictors. The score prognostic capability was compared in both groups.
  
  RESULTS:
  During a median follow-up of 31 months, 1230 patients died: 622 (9%) in the modelling and 608 (9%) in the validation group (p=0.68). Independent predictors of mortality were ischaemia at SE (HR 1.77, 95%?CI 1.49 to 2.12; p
  CONCLUSIONS:
  Simple clinical variables may be able to optimise SE risk stratification.
  
  © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
  
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• Association Between Elevated Pulse Pressure and High Resting Coronary Blood Flow Velocity in Patients With Angiographically Normal Epicardial Coronary Arteries.
  J Am Heart Assoc

  2017 Jun;6(7):. doi: e005710.
  
  Lembo Maria, Sicari Rosa, Esposito Roberta, Rigo Fausto, Cortigiani Lauro, Lo Iudice Francesco, Picano Eugenio, Trimarco Bruno, Galderisi Maurizio
  
  Abstract
  
  BACKGROUND:
  The aim of our study was to evaluate the relationship of pulse pressure (PP), a raw index of arterial stiffness, with noninvasively determined coronary flow reserve (CFR) and its components, in patients with angiographically normal epicardial coronary arteries.
  
  METHODS AND RESULTS:
  The study population included 398 patients without angiographic evidence of coronary stenosis, who underwent high-dose dipyridamole stress echocardiography with transthoracic-derived CFR evaluation on the left anterior descending artery. CFR was calculated as the ratio between high-dose dipyridamole and resting coronary diastolic peak velocities. Patients were divided into 2 groups: the first group included the first and second PP tertiles (n=298, PP ?60 mm Hg) and the second group included the highest PP tertile (n=100, PP >60 mm Hg). Mean blood pressure, systolic blood pressure (both
  CONCLUSIONS:
  In patients without epicardial coronary artery stenosis, the highest PP tertile is associated with an increased coronary flow velocity at rest.
  
  © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
  
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• Stress echo in Italy: state-of-the-art 2015.
  J Cardiovasc Med (Hagerstown)

  2017 Aug;18(8):637-639. doi: 10.2459/JCM.0000000000000530.
  
  Ciampi Quirino, Citro Rodolfo, Severino Sergio, Labanti Graziana, Cortigiani Lauro, Sicari Rosa, Gaibazzi Nicola, Galderisi Maurizio, Bossone Eduardo, Colonna Paolo, Picano Eugenio,
  
  
  
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• Pulmonary congestion evaluated by lung ultrasound predicts decompensation in heart failure outpatients.
  Int J Cardiol

  2017 Aug;240():271-278. doi: 10.1016/j.ijcard.2017.02.150.
  
  Miglioranza Marcelo H, Picano Eugenio, Badano Luigi P, Sant'Anna Roberto, Rover Marciane, Zaffaroni Facundo, Sicari Rosa, Kalil Renato K, Leiria Tiago L, Gargani Luna
  
  Abstract
  
  BACKGROUND:
  Pulmonary congestion is the main cause of hospital admission among heart failure (HF) patients. Lung ultrasound (LUS) assessment of B-lines has been recently proposed as a reliable and easy tool for evaluating pulmonary congestion.
  
  OBJECTIVE:
  To determine the prognostic value of LUS in predicting adverse events in HF outpatients.
  
  METHODS:
  Single-center prospective cohort of 97 moderate-to-severe systolic HF patients (53±13years; 61% males) consecutively enrolled between November 2011 and October 2012. LUS evaluation was performed during the regular outpatient visit to evaluate the presence of pulmonary congestion, determined by B-lines number. Patients were followed up for 4months to assess admission due to acute pulmonary edema.
  
  RESULTS:
  During follow-up period (106±12days), 21 hospitalizations for acute pulmonary edema occurred. At Cox regression analysis, B-lines number?30 (HR 8.62; 95%CI: 1.8-40.1; p=0.006) identified a group at high risk for acute pulmonary edema admission at 120days, and was the strongest predictor of events compared to other established clinical, laboratory and instrumental findings. No acute pulmonary edema occurred in patients without significant pulmonary congestion at LUS (number of B-lines
  CONCLUSION:
  In a HF outpatient setting, B-line assessment by LUS identifies patients more likely to be admitted for decompensated HF in the following 4months. This simple evaluation could allow prompt therapy optimization in those patients who, although asymptomatic, carry a significant degree of extravascular lung water.
  
  CONDENSED ABSTRACT:
  Pulmonary congestion is the main cause of hospital admissions among heart failure patients. Lung ultrasound can be used as a reliable and easy way to evaluate pulmonary congestion through assessment of B-lines. In a cohort of heart failure outpatients, a B-lines cutoff?30 (HR 8.62; 95%CI: 1.8-40.1) identified patients most likely to develop acute pulmonary edema at 120-days.
  
  Copyright © 2017 Elsevier B.V. All rights reserved.
  
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• Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function.
  Eur J Neurosci

  2017 May;45(10):1279-1288. doi: 10.1111/ejn.13565.
  
  Tonacci Alessandro, Bruno Rosa M, Ghiadoni Lorenzo, Pratali Lorenza, Berardi Nicoletta, Tognoni Gloria, Cintoli Simona, Volpi Leda, Bonuccelli Ubaldo, Sicari Rosa, Taddei Stefano, Maffei Lamberto, Picano Eugenio
  
  Abstract
  
  Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (? =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI.
  
  © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
  
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• The clinical use of stress echocardiography in ischemic heart disease.
  Cardiovasc Ultrasound

  2017 Mar;15(1):7. doi: 7.
  
  Sicari Rosa, Cortigiani Lauro
  
  Abstract
  
  Stress echocardiography is an established technique for the assessment of extent and severity of coronary artery disease. The combination of echocardiography with a physical, pharmacological or electrical stress allows to detect myocardial ischemia with an excellent accuracy. A transient worsening of regional function during stress is the hallmark of inducible ischemia. Stress echocardiography provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging or magnetic resonance, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician.The evidence on its clinical impact has been collected over 35 years, based on solid experimental, pathophysiological, technological and clinical foundations. There is the need to implement the combination of wall motion and coronary flow reserve, assessed in the left anterior descending artery, into a single test. The improvement of technology and in imaging quality will make this approach more and more feasible. The future issues in stress echo will be the possibility of obtaining quantitative information translating the current qualitative assessment of regional wall motion into a number. The next challenge for stress echocardiography is to overcome its main weaknesses: dependance on operator expertise, the lack of outcome data (a widesperad problem in clinical imaging) to document the improvement of patient outcomes. This paper summarizes the main indications for the clinical applications of stress echocardiography to ischemic heart disease.
  
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• Stress echocardiography: no more challenges!
  Eur Heart J Cardiovasc Imaging

  2017 Apr;18(4):422-423. doi: 10.1093/ehjci/jew225.
  
  Sicari Rosa
  
  
  
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• Dual-Imaging Stress Echocardiography for Prognostic Assessment of High-Risk Asymptomatic Patients with Diabetes Mellitus.
  J Am Soc Echocardiogr

  2017 Feb;30(2):149-158. doi: 10.1016/j.echo.2016.10.003.
  
  Cortigiani Lauro, Gherardi Sonia, Faggioni Michela, Bovenzi Francesco, Picano Eugenio, Petersen Christina, Molinaro Sabrina, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  In patients with diabetes, the utility of diagnostic screening cardiac tests in subjects without clinical coronary artery disease remains controversial. The aim of this study was to assess the prognostic meaning of dual-imaging stress echocardiography (conventional wall motion analysis and Doppler-derived coronary flow velocity reserve [CFVR] of the left anterior descending coronary artery) in high-risk asymptomatic individuals with diabetes.
  
  METHODS:
  This was a prospective analysis of 230 asymptomatic patients with diabetes (128 men; mean age, 66 ± 9 years) with no clinical evidence of coronary artery disease, no Q waves or deep negative waves on the electrocardiogram, and no wall motion abnormalities on resting echocardiography. Of these subjects, 147 (64%) had target organ damage and 83 (36%) had two or more associated cardiovascular risk factors. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler, and test results were entered into a database at the time of testing for a clinical and outcome follow-up (mean, 4.6 ± 2.7 years).
  
  RESULTS:
  Inducible ischemia and reduced CFVR (?2) were detected in six and 52 patients, respectively. A total of 54 subjects (23%) had abnormal test results (ischemia or reduced CFVR). During follow-up, 39 major adverse cardiac events (MACEs) occurred: 22 hard events (18 deaths and four nonfatal myocardial infarctions) and 17 coronary revascularizations. The yearly incidence rates of hard events and MACEs in the entire study population were 2.1% and 3.6%, respectively. Abnormal test results were the only multivariate indicator of both hard events (hazard ratio, 3.69; 95% CI, 1.54-8.80) and MACEs (hazard ratio, 6.12; 95% CI, 3.22-11.62).
  
  CONCLUSIONS:
  Abnormal test results were obtained in one of four cases and were a strong and independent predictor of future hard events and MACEs.
  
  Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
  
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• The declining frequency of inducible myocardial ischemia during stress echocardiography over 27 consecutive years (1983-2009).
  Int J Cardiol

  2016 Dec;224():57-61. doi: 10.1016/j.ijcard.2016.08.313.
  
  Carpeggiani Clara, Landi Patrizia, Michelassi Claudio, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Previous studies have suggested a decline in positivity of stress cardiac imaging, suggesting the need for developing better strategies for test selection to achieve acceptable cost-effectiveness balance. The aim of this retrospective study was to assess the rate of positivity of stress echocardiography (SE) over 27 consecutive years.
  
  METHODS:
  We assessed the rate of SE positivity in 2007 patients without previous myocardial infarction or coronary revascularization who performed SE in a tertiary care referral center from 1983 to 2009. SE was performed with dipyridamole (1427), dobutamine (136) or exercise (444).
  
  RESULTS:
  There was a progressive decline over time in the rate of SE positivity from 42% (1983-1991) to 22% (2001-2009), with a relative increase of patients with low pre-test probability of disease (from 5% to 27%). The percentage of patients studied with SE under anti-ischemic therapy increased markedly (from 8% in the first to 61% in the last nine years).
  
  CONCLUSION:
  Over 27 consecutive years, we observed a steady decline in SE positivity rate (with >5-fold increase of low probability patients), with almost 8-fold increase in anti-ischemic therapy at testing. We probably need refined criteria of referral for testing and/or better ways to titrate the negative response beyond wall motion abnormalities during SE.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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• Left ventricular dysfunction in repaired tetralogy of Fallot: incidence and impact on atrial arrhythmias at long term-follow up.
  Int J Cardiovasc Imaging

  2016 Sep;32(9):1441-1449.
  
  Ait Ali Lamia, Trocchio GianLuca, Crepaz Roberto, Stuefer Josef, Stagnaro Nicola, Siciliano Valeria, Molinaro Sabrina, Sicari Rosa, Festa Pierluigi
  
  Abstract
  
  Left ventricle (LV) systolic dysfunction in repaired tetralogy of Fallot (TOF) has been identified as a risk factor for functional status and adverse outcome. The aims of this cross-sectional followed by a prospective study were: (1) to evaluate the prevalence of LV systolic dysfunction in a large cohort of adults with repaired tetralogy of Fallot, (2) to test the relationship between LV systolic dysfunction and other known risk factors and (3) to evaluate the impact of LV systolic dysfunction on adverse cardiac events. In a multicenter study, 237 adults repaired TOF (58?% males, age 30?±?10 years) were evaluated by cardiac magnetic resonance (CMR). Demographics, surgical history, ECG, Echo-Color Doppler and follow-up data were recorded. LV was dilated (Z value >2) in 16 patients (6?%), however 56 patients (23.6?%) had a reduced LV systolic function left ventricle ejection fraction (LVEF) (Z value
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• Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.
  Nephrol Dial Transplant

  2016 Dec;31(12):1982-1988.
  
  Gargani Luna, Sicari Rosa, Raciti Mauro, Serasini Luca, Passera Mirko, Torino Claudia, Letachowicz Krzysztof, Ekart Robert, Fliser Danilo, Covic Adrian, Balafa Olga, Stavroulopoulos Aristeidis, Massy Ziad A, Fiaccadori Enrico, Caiazza Alberto, Bachelet Thomas, Slotki Itzchak, Shavit Linda, Martinez-Castelao Alberto, Coudert-Krier Marie-Jeanne, Rossignol Patrick, Kraemer Thomas Daniel, Hannedouche Thierry, Panichi Vincenzo, Wiecek Andrzej, Pontoriero Giuseppe, Sarafidis Pantelis, Klinger Marian, Hojs Radovan, Seiler-Mußler Sarah, Lizzi Fabio, Onofriescu Mihai, Zarzoulas Fotis, Tripepi Rocco, Mallamaci Francesca, Tripepi Giovanni, Picano Eugenio, London Gérard Michel, Zoccali Carmine
  
  Abstract
  
  Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P
  © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
  
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• The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study.
  Clin J Am Soc Nephrol

  2016 Nov;11(11):2005-2011.
  
  Torino Claudia, Gargani Luna, Sicari Rosa, Letachowicz Krzysztof, Ekart Robert, Fliser Danilo, Covic Adrian, Siamopoulos Kostas, Stavroulopoulos Aristeidis, Massy Ziad A, Fiaccadori Enrico, Caiazza Alberto, Bachelet Thomas, Slotki Itzchak, Martinez-Castelao Alberto, Coudert-Krier Marie-Jeanne, Rossignol Patrick, Gueler Faikah, Hannedouche Thierry, Panichi Vincenzo, Wiecek Andrzej, Pontoriero Giuseppe, Sarafidis Pantelis, Klinger Marian, Hojs Radovan, Seiler-Mussler Sarah, Lizzi Fabio, Siriopol Dimitrie, Balafa Olga, Shavit Linda, Tripepi Rocco, Mallamaci Francesca, Tripepi Giovanni, Picano Eugenio, London Gérard Michel, Zoccali Carmine
  
  Abstract
  
  BACKGROUND AND OBJECTIVES:
  Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown.
  
  DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
  In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema.
  
  RESULTS:
  Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and ?-statistics (? ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs.
  
  CONCLUSIONS:
  Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.
  
  Copyright © 2016 by the American Society of Nephrology.
  
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• Arsenic and subclinical vascular damage in a sample of Italian young adults: a cross-sectional analysis.
  Environ Sci Pollut Res Int

  2016 Oct;23(20):20307-20314.
  
  Stea Francesco, Faita Francesco, Borghini Andrea, Faita Francesca, Bianchi Fabrizio, Bustaffa Elisa, Minichilli Fabrizio, Andreassi Maria Grazia, Sicari Rosa
  
  Abstract
  
  Exposure to arsenic (As) increases cardiovascular risk. The purpose of this study was to evaluate the relationship between As and intima-media thickness (IMT) in the common carotid artery and common genetic variants in genes implicated in As metabolism (ASIIIMT Met287Thr, GSTT1+/-, and GSTM1+/-) and DNA repair (hOGG1 Ser326Cys and XRCC1 Arg399Ser). Two hundred and fourteen healthy volunteers, age 20-46, were recruited in four zones polluted by As. Urine samples were tested for total As, inorganic As (iAs), monomethylarsinic (MMA), and dimethylarsinic acid (DMA). Primary and secondary methylation index (PMI, SMI) were computed as MMA/iAs and DMA/MMA. Common carotid artery scans were obtained by high-resolution ultrasound. There was no correlation between IMT and total As, iAs, iAs + MMA + DMA, PMI, or SMI. However, the increase of IMT with age was higher than that observed in the healthy population, both in males (6.25 vs. 5.20 ?m/year) and, to a lesser extent, in females (5.05 vs. 4.97 ?m/year). After correction for age and gender, subjects with a high urinary As level (?3.86 ?g/L) and carriers of the GSTT1-positive (+) genotype also had higher IMT than those with a low urinary level and the GSTT1-null (-) genotype (0.56 [0.48-0.64] vs. 0.53 [0.44-0.62] mm, p = 0.010). The analysis hints at faster vascular aging as compared to the healthy population. Our findings also suggested that GSTT1 and hOGG1 gene polymorphisms might play an important role in the individual risk of As-induced carotid atherosclerosis.
  
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• Carotid-Ventricular Coupling During Exercise: A Pilot Study.
  J Ultrasound Med

  2016 Aug;35(8):1747-56. doi: 10.7863/ultra.15.08059.
  
  Bianchini Elisabetta, Bruno Rosa Maria, Pitino Annalisa, Di Lascio Nicole, Petersen Christina, Molinaro Sabrina, Faita Francesco, Gemignani Vincenzo, Ghiadoni Lorenzo, Sicari Rosa
  
  Abstract
  
  OBJECTIVES:
  To evaluate carotid elasticity and left ventricular elastance during a graded bicycle semisupine exercise test in patients with known or suspected coronary artery disease and compare them with a control group of healthy young volunteers.
  
  METHODS:
  Thirty-six elderly patients and 18 young healthy volunteers were recruited. The right carotid diameter was estimated by an automatic system applied to B-mode sonographic sequences, central mean blood and pulse pressures by radial artery tonometry, and cardiac volumes by 2-dimensional transthoracic echocardiography; from these direct measurements, the carotid cross-sectional distensibility coefficient and left ventricular elastance index were obtained. Analyses were performed at rest, at peak stress, and during the recovery phase.
  
  RESULTS:
  The elderly patients included 20 men (mean age ± SD, 61 ± 8 years); the volunteers included 9 men (mean age, 34 ± 3 years). The mean blood pressure (at rest: patients, 97 ± 7 mm Hg; controls, 93 ± 9 mm Hg; not significant) increased similarly in both groups during exercise and decreased during the recovery phase. The diameter was higher in patients than controls (7.5 ± 1.1 versus 6.2 ± 0.5 mm) and increased significantly with exercise only in the latter group (at peak: 6.5 ± 0.6 mm; P
  CONCLUSIONS:
  In older patients with multiple cardiovascular risk factors or established coronary artery disease, an abnormal carotid-ventricular adaptation to exercise was observed when compared to young healthy individuals.
  
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• Prognostic role of stress echocardiography in hypertrophic cardiomyopathy: The International Stress Echo Registry.
  Int J Cardiol

  2016 Sep;219():331-8. doi: 10.1016/j.ijcard.2016.06.044.
  
  Ciampi Quirino, Olivotto Iacopo, Gardini Chiara, Mori Fabio, Peteiro Jesus, Monserrat Lorenzo, Fernandez Xusto, Cortigiani Lauro, Rigo Fausto, Lopes Luis Rocha, Cruz Ines, Cotrim Carlos, Losi Mariangela, Betocchi Sandro, Beleslin Branko, Tesic Milorad, Dikic Ana Djordjevic, Lazzeroni Ettore, Lazzeroni Davide, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Stress echo (SE) may have a role in the outcome in patients with hypertrophic cardiomyopathy (HCM).
  
  OBJECTIVES:
  The aim was to assess the prognostic value of SE in a retrospective multicenter study in HCM.
  
  METHODS:
  We enrolled 706 HCM patients. The employed stress was exercise (n=608) and/or vasodilator (n=146, dipyridamole in 98 and adenosine in 48). We defined SE positivity according to clinical/hemodynamic criteria including: symptoms (all stress modalities), exercise-induced hypotension (failure to increase or fall >20mmHg, exercise) and exercise-induced left ventricular outflow tract obstruction (left ventricular outflow tract obstruction >50mmHg); and ischemic criteria, such as new wall motion abnormalities (new wall motion abnormality) and/or reduction of coronary flow reserve velocity (CFVR?2.0) on left anterior descending coronary artery with vasodilator stress assessed in 116 patients. All patients completed the clinical follow-up.
  
  RESULTS:
  Positive SE showed more frequently CFVR reduction, exercise-induced hypotension, left ventricular outflow tract obstruction, and symptoms (38, 23, 20 and 15% respectively), but new wall motion abnormality only in 6%. During a median follow-up of 49months 180 events were observed, including 40 deaths. Clinical/hemodynamic criteria did not predict outcome (X2 0.599, p=0.598), whereas ischemia-related SE criteria (X2: 111.120, p
  CONCLUSIONS:
  SE has an important prognostic significance in HCM patients, with ischemia-related end-points showing greater predictive accuracy than hemodynamic endpoints. New wall motion abnormalities and impairment of CFVR should be specifically included in SE protocols for HCM.
  
  Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
  
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• Hypertension in Chronic Kidney Disease Part 1: Out-of-Office Blood Pressure Monitoring: Methods, Thresholds, and Patterns.
  Hypertension

  2016 Jun;67(6):1093-101. doi: 10.1161/HYPERTENSIONAHA.115.06895.
  
  Parati Gianfranco, Ochoa Juan Eugenio, Bilo Grzegorz, Agarwal Rajiv, Covic Adrian, Dekker Friedo W, Fliser Danilo, Heine Gunnar H, Jager Kitty J, Gargani Luna, Kanbay Mehmet, Mallamaci Francesca, Massy Ziad, Ortiz Alberto, Picano Eugenio, Rossignol Patrick, Sarafidis Pantelis, Sicari Rosa, Vanholder Raymond, Wiecek Andrzej, London Gerard, Zoccali Carmine,
  
  
  
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• Hypertension in Chronic Kidney Disease Part 2: Role of Ambulatory and Home Blood Pressure Monitoring for Assessing Alterations in Blood Pressure Variability and Blood Pressure Profiles.
  Hypertension

  2016 Jun;67(6):1102-10. doi: 10.1161/HYPERTENSIONAHA.115.06896.
  
  Parati Gianfranco, Ochoa Juan Eugenio, Bilo Grzegorz, Agarwal Rajiv, Covic Adrian, Dekker Friedo W, Fliser Danilo, Heine Gunnar H, Jager Kitty J, Gargani Luna, Kanbay Mehmet, Mallamaci Francesca, Massy Ziad, Ortiz Alberto, Picano Eugenio, Rossignol Patrick, Sarafidis Pantelis, Sicari Rosa, Vanholder Raymond, Wiecek Andrzej, London Gerard, Zoccali Carmine,
  
  
  
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• Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population.
  Eur Heart J Cardiovasc Imaging

  2016 Sep;17(9):951-60. doi: 10.1093/ehjci/jew038.
  
  Liga Riccardo, Vontobel Jan, Rovai Daniele, Marinelli Martina, Caselli Chiara, Pietila Mikko, Teresinska Anna, Aguadé-Bruix Santiago, Pizzi Maria Nazarena, Todiere Giancarlo, Gimelli Alessia, Chiappino Dante, Marraccini Paolo, Schroeder Stephen, Drosch Tanja, Poddighe Rosa, Casolo Giancarlo, Anagnostopoulos Constantinos, Pugliese Francesca, Rouzet Francois, Le Guludec Dominique, Cappelli Francesco, Valente Serafina, Gensini Gian Franco, Zawaideh Camilla, Capitanio Selene, Sambuceti Gianmario, Marsico Fabio, Filardi Pasquale Perrone, Fernández-Golfín Covadonga, Rincón Luis M, Graner Frank P, de Graaf Michiel A, Stehli Julia, Reyes Eliana, Nkomo Sandy, Mäki Maija, Lorenzoni Valentina, Turchetti Giuseppe, Carpeggiani Clara, Puzzuoli Stefano, Mangione Maurizio, Marcheschi Paolo, Giannessi Daniela, Nekolla Stephan, Lombardi Massimo, Sicari Rosa, Scholte Arthur J H A, Zamorano José L, Underwood S Richard, Knuuti Juhani, Kaufmann Philipp A, Neglia Danilo, Gaemperli Oliver,
  
  Abstract
  
  AIMS:
  Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting.
  
  METHODS AND RESULTS:
  Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR?0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively.
  
  CONCLUSION:
  In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
  
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• Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.
  Arterioscler Thromb Vasc Biol

  2016 Apr;36(4):757-64. doi: 10.1161/ATVBAHA.115.306818.
  
  Caselli Chiara, Prontera Concetta, Liga Riccardo, De Graaf Michiel A, Gaemperli Oliver, Lorenzoni Valentina, Ragusa Rosetta, Marinelli Martina, Del Ry Silvia, Rovai Daniele, Giannessi Daniela, Aguade-Bruix Santiago, Clemente Alberto, Bax Jeroen J, Lombardi Massimo, Sicari Rosa, Zamorano José, Scholte Arthur J, Kaufmann Philipp A, Knuuti Juhani, Underwood S Richard, Clerico Aldo, Neglia Danilo
  
  Abstract
  
  OBJECTIVE:
  Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD.
  
  APPROACH AND RESULTS:
  Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P
  CONCLUSIONS:
  In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.
  
  © 2016 American Heart Association, Inc.
  
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• Left Bundle Branch Block Negatively Affects Coronary Flow Velocity Reserve and Myocardial Contractile Reserve in Nonischemic Dilated Cardiomyopathy.
  J Am Soc Echocardiogr

  2016 Feb;29(2):112-8. doi: 10.1016/j.echo.2015.08.012.
  
  Ciampi Quirino, Cortigiani Lauro, Pratali Lorenza, Rigo Fausto, Villari Bruno, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery (LAD) and myocardial contractile reserve are often impaired in nonischemic dilated cardiomyopathy (DCM). Whether they are affected by the presence of left bundle branch block (LBBB) remains unaddressed. The aim of the study was to investigate how LBBB influences CFVR of the LAD and myocardial contractile reserve in patients with DCM.
  
  METHODS:
  One hundred eighty-one patients with DCM (116 men; mean age, 63 ± 12 years) underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFVR evaluation of the LAD by Doppler. All patients had ejection fractions  2.0 was considered normal. Inotropic reserve was defined as rest-stress variation in wall motion score index ? 0.20. This was a prospective analysis of an unselected sample consecutively enrolled and retrospectively selected.
  
  RESULTS:
  The study group was separated on the basis of presence (n = 122) or absence (n = 59) of LBBB. Patients with LBBB were older (64 ± 11 vs 59 ± 12 years, P = .004) and had reduced resting ejection fractions (30 ± 9% vs 33 ± 7%, P = .02), CFVR of the LAD (1.96 ± 0.41 vs 2.23 ± 0.73, P = .001), and myocardial contractile reserve (variation in wall motion score index, -0.18 ± 0.17 vs -0.33 ± 0.28; P 
  CONCLUSIONS:
  CFVR during vasodilator stress echocardiography is a suitable tool for assessing microvascular dysfunction in routine clinical practice. Patients with DCM and LBBB show more severe forms of microvascular dysfunction, which is related to worse left ventricular function and lack of contractile reserve. Therapeutic interventions to restore microvascular function may improve left ventricular function parameters in patients with DCM.
  
  Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
  
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• Prognostic models in coronary artery disease: Cox and network approaches.
  R Soc Open Sci

  2015 Feb;2(2):140270. doi: 140270.
  
  Mora Antonio, Sicari Rosa, Cortigiani Lauro, Carpeggiani Clara, Picano Eugenio, Capobianco Enrico
  
  Abstract
  
  Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84?mg?kg(-1) over 6?min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic factors involved in prognostic stratification whose complexity suggests an exploration beyond the analysis provided by the still fundamental Cox approach.
  
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• A New Integrated Clinical-Biohumoral Model to Predict Functionally Significant Coronary Artery Disease in Patients With Chronic Chest Pain.
  Can J Cardiol

  2015 Jun;31(6):709-16. doi: 10.1016/j.cjca.2015.01.035.
  
  Caselli Chiara, Rovai Daniele, Lorenzoni Valentina, Carpeggiani Clara, Teresinska Anna, Aguade Santiago, Todiere Giancarlo, Gimelli Alessia, Schroeder Stephen, Casolo Giancarlo, Poddighe Rosa, Pugliese Francesca, Le Guludec Dominique, Valente Serafina, Sambuceti Gianmario, Perrone-Filardi Pasquale, Del Ry Silvia, Marinelli Martina, Nekolla Stephan, Pietila Mikko, Lombardi Massimo, Sicari Rosa, Scholte Arthur, Zamorano José, Kaufmann Philipp A, Underwood S Richard, Knuuti Juhani, Giannessi Daniela, Neglia Danilo,
  
  Abstract
  
  BACKGROUND:
  In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain.
  
  METHODS:
  In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Evaluation of Integrated Cardiac Imaging (EVINCI) study, clinical and biohumoral data were collected.
  
  RESULTS:
  Functionally significant CAD-ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR
  CONCLUSIONS:
  The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD.
  
  Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
  
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• Prediction of mortality by stress echocardiography in 2835 diabetic and 11?305 nondiabetic patients.
  Circ Cardiovasc Imaging

  2015 May;8(5):. doi: e002757.
  
  Cortigiani Lauro, Borelli Lucia, Raciti Mauro, Bovenzi Francesco, Picano Eugenio, Molinaro Sabrina, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  To compare the capability by stress echocardiography results to predict overall mortality in a large unselected cohort of diabetic and nondiabetic patients.
  
  METHODS AND RESULTS:
  The study group comprised 14?140 patients (2835 diabetics and 11?305 nondiabetics) who underwent stress echocardiography for evaluation of known (n=5671) or suspected (n=8469) coronary artery disease. Ischemia at stress echocardiography was observed in 768 (27%) diabetics and 2644 (23%) nondiabetics. During a median follow-up of 30 months (first quartile, 9; third quartile, 63), 1213 patients died. In diabetics, multivariable indicators of mortality were age (hazard ratio [HR], 1.07, 95% confidence interval [CI], 1.06-1.09), rest wall motion abnormality (HR, 2.43; 95% CI, 1.83-3.22), and ischemia at stress echocardiography (HR, 1.71; 95% CI, 1.34-2.18). In nondiabetics, multivariable indicators of mortality were age (HR, 1.07; 95% CI, 1.06-1.08), rest wall motion abnormality (HR, 2.19; 95% CI, 1.86-2.57), male sex (HR, 1.65; 95% CI, 1.41-1.93), ischemia at stress echocardiography (HR, 1.54; 95% CI, 1.32-1.80), and antischemic therapy at the time of test (HR, 1.15; 95% CI, 1.00-1.32). In stress echo negative subjects for ischemia, antischemic therapy showed increased annual mortality in nondiabetic patients with (3.8% versus 3.1%; P=0.04) or without rest wall motion abnormality (1.6% versus 0.9%; P
  CONCLUSIONS:
  Ischemia at stress echocardiography is a strong and independent predictor of total mortality in diabetic as well as nondiabetic patients. Antischemic therapy markedly affects the negative predictive value of stress echocardiography in nondiabetic patients, whereas it is prognostically neutral in the diabetic population.
  
  © 2015 American Heart Association, Inc.
  
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• Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.
  Eur Heart J Cardiovasc Imaging

  2015 Mar;16(3):281-97. doi: 10.1093/ehjci/jeu129.
  
  Valsangiacomo Buechel E R, Grosse-Wortmann L, Fratz S, Eichhorn J, Sarikouch S, Greil G F, Beerbaum P, Bucciarelli-Ducci C, Bonello B, Sieverding L, Schwitter J, Helbing W A, , Galderisi Maurizio, Miller Owen, Sicari Rosa, Rosa John, Thaulow Erik, Edvardsen Thor, Brockmeier Konrad, Qureshi Shakeel, Stein Joerg
  
  Abstract
  
  This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
  
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• Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.
  Circ Cardiovasc Imaging

  2015 Mar;8(3):. doi: e002179.
  
  Neglia Danilo, Rovai Daniele, Caselli Chiara, Pietila Mikko, Teresinska Anna, Aguadé-Bruix Santiago, Pizzi Maria Nazarena, Todiere Giancarlo, Gimelli Alessia, Schroeder Stephen, Drosch Tanja, Poddighe Rosa, Casolo Giancarlo, Anagnostopoulos Constantinos, Pugliese Francesca, Rouzet Francois, Le Guludec Dominique, Cappelli Francesco, Valente Serafina, Gensini Gian Franco, Zawaideh Camilla, Capitanio Selene, Sambuceti Gianmario, Marsico Fabio, Perrone Filardi Pasquale, Fernández-Golfín Covadonga, Rincón Luis M, Graner Frank P, de Graaf Michiel A, Fiechter Michael, Stehli Julia, Gaemperli Oliver, Reyes Eliana, Nkomo Sandy, Mäki Maija, Lorenzoni Valentina, Turchetti Giuseppe, Carpeggiani Clara, Marinelli Martina, Puzzuoli Stefano, Mangione Maurizio, Marcheschi Paolo, Mariani Fabio, Giannessi Daniela, Nekolla Stephan, Lombardi Massimo, Sicari Rosa, Scholte Arthur J H A, Zamorano José L, Kaufmann Philipp A, Underwood S Richard, Knuuti Juhani,
  
  Abstract
  
  BACKGROUND:
  The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD.
  
  METHODS AND RESULTS:
  A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ?1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ?0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P
  CONCLUSIONS:
  In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively.
  
  CLINICAL TRIAL REGISTRATION URL:
  http://www.clinicaltrials.gov. Unique identifier: NCT00979199.
  
  © 2015 American Heart Association, Inc.
  
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• Role of multimodality cardiac imaging in the management of patients with hypertrophic cardiomyopathy: an expert consensus of the European Association of Cardiovascular Imaging Endorsed by the Saudi Heart Association.
  Eur Heart J Cardiovasc Imaging

  2015 Mar;16(3):280. doi: 10.1093/ehjci/jeu291.
  
  Cardim Nuno, Galderisi Maurizio, Edvardsen Thor, Plein Sven, Popescu Bogdan A, D'Andrea Antonello, Bruder Oliver, Cosyns Bernard, Davin Laurent, Donal Erwan, Freitas Antonio, Habib Gilbert, Kitsiou Anastasia, Petersen Steffen E, Schroeder Stephen, Lancellotti Patrizio, Camici Paolo, Dulgheru Raluca, Hagendorff Andreas, Lombardi Massimo, Muraru Denisa, Sicari Rosa
  
  Abstract
  
  Taking into account the complexity and limitations of clinical assessment in hypertrophic cardiomyopathy (HCM), imaging techniques play an essential role in the evaluation of patients with this disease. Thus, in HCM patients, imaging provides solutions for most clinical needs, from diagnosis to prognosis and risk stratification, from anatomical and functional assessment to ischaemia detection, from metabolic evaluation to monitoring of treatment modalities, from staging and clinical profiles to follow-up, and from family screening and preclinical diagnosis to differential diagnosis. Accordingly, a multimodality imaging (MMI) approach (including echocardiography, cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging) is encouraged in the assessment of these patients. The choice of which technique to use should be based on a broad perspective and expert knowledge of what each technique has to offer, including its specific advantages and disadvantages. Experts in different imaging techniques should collaborate and the different methods should be seen as complementary, not as competitors. Each test must be selected in an integrated and rational way in order to provide clear answers to specific clinical questions and problems, trying to avoid redundant and duplicated information, taking into account its availability, benefits, risks, and cost.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
  
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• Prognostic value of Doppler echocardiographic-derived coronary flow velocity reserve of left anterior descending artery in octogenarians with stress echocardiography negative for wall motion criteria.
  Eur Heart J Cardiovasc Imaging

  2015 Jun;16(6):653-60. doi: 10.1093/ehjci/jeu311.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  AIMS:
  Doppler-derived coronary flow velocity reserve (CFVR) of left anterior descending (LAD) artery is an effective tool to predict overall mortality. The aim was to investigate the capability of CFVR to predict outcome in an unselected cohort of patients older than 80 years having stress echo negative by wall motion criteria.
  
  METHODS AND RESULTS:
  The study group refers to 369 patients aged > 80 years (156 men; mean age 83 ± 2 years) who had undergone dipyridamole stress echocardiography with CFVR assessment of LAD artery of known (n = 144) or suspected (n = 225) coronary artery disease. Stress echocardiography was negative for wall motion criteria in all cases. Mean CFVR was 2.07 ± 0.53. During a median follow-up of 21 months, there were 62 major adverse cardiac events (MACEs; 45 deaths and 17 non-fatal myocardial infarctions). With a receiver operating characteristic analysis, a CFVR of ? 1.93 was the best cut-off for predicting mortality and MACE. At individual patient analysis, 152 (41%) subjects had a CFVR of 1.93 (P = 0.001); an annual MACE rate was 14.8% in the former and 4.5% in the latter (P
  CONCLUSIONS:
  A reduced CFVR of LAD artery is a strong and independent indicator of both mortality and MACE, adding prognostic information over clinical evaluation and RWMA. Conversely, a preserved CFVR predicts a favourable outcome particularly in subjects with no RWMA.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
  
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• [Point-of-care ultrasound: physical examination of the third millennium? listen and look].
  G Ital Cardiol (Rome)

  2014 Nov;15(11):605-6. doi: 10.1714/1694.18502.
  
  Sicari Rosa
  
  
  
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• Role of stress echocardiography in operated fallot: feasibility and detection of right ventricular response.
  J Am Soc Echocardiogr

  2014 Dec;27(12):1319-28. doi: 10.1016/j.echo.2014.08.006.
  
  Ait-Ali Lamia, Siciliano Valeria, Passino Claudio, Molinaro Sabrina, Pasanisi Emilio, Sicari Rosa, Pingitore Alessandro, Festa Pierluigi
  
  Abstract
  
  BACKGROUND:
  Patients with repaired tetralogy of Fallot often present residual hemodynamic abnormalities leading to right ventricular (RV) burden. Semisupine exercise echocardiography (Ex-Echo) is a validated method for diagnosis and prognosis in ischemic and valvular heart diseases and has potential for the evaluation of RV burden, pressure, and function. The aims of this study were to assess the effect of exercise on the right ventricle in adults with repaired tetralogy of Fallot and to identify factors associated with decreased RV function at peak exercise in an observational study.
  
  METHODS:
  A total of 128 patients with repaired tetralogy of Fallot referred to an outpatient congenital heart disease unit were evaluated by Ex-Echo and conventional clinical and diagnostic examinations (i.e., electrocardiography, transthoracic echocardiography, cardiovascular magnetic resonance, cardiopulmonary exercise testing, and N-terminal pro-brain natriuretic peptide assay). The following Ex-Echo parameters were measured at rest and at peak exercise: tricuspid annular plane systolic excursion, RV pressure, and RV fractional area change (FAC).
  
  RESULTS:
  Interpretable images for RV FAC analysis were obtained in 123 of 128 patients. In 91 of 128 with detectable tricuspid valve regurgitation, RV systolic pressure during exercise was evaluated. According to positive or negative RV FAC variation during exercise, 74 patients were respectively defined as "responders" on stress echocardiography and 49 as "nonresponders"; the median percentage change between rest and stress was 13.8% (interquartile range, 5.9% to 26.9%) in responders and -13.5% (interquartile range, -25.4% to -7.4%) in nonresponders. Systolic RV systolic pressure increased in a similar manner in the two groups (65 ± 36% in responders vs 59 ± 39% in nonresponders, P = .45). Tricuspid annular plane systolic excursion increased significantly during peak exercise in responders from 17.2 ± 3.4 mm at rest to 19.7 ± 4.3 mm (P 
  CONCLUSIONS:
  Ex-Echo is feasible in patients with repaired tetralogy of Fallot and allows the integrated assessment of variation in RV systolic pressure, area, and function during exercise, which usefully complement more conventional indices of hemodynamic burden in these patients. Longitudinal follow-up is needed to better delineate the prognostic value of the results of Ex-Echo.
  
  Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
  
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• Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
  Eur Heart J Cardiovasc Imaging

  2014 Oct;15(10):1063-93. doi: 10.1093/ehjci/jeu192.
  
  Plana Juan Carlos, Galderisi Maurizio, Barac Ana, Ewer Michael S, Ky Bonnie, Scherrer-Crosbie Marielle, Ganame Javier, Sebag Igal A, Agler Deborah A, Badano Luigi P, Banchs Jose, Cardinale Daniela, Carver Joseph, Cerqueira Manuel, DeCara Jeanne M, Edvardsen Thor, Flamm Scott D, Force Thomas, Griffin Brian P, Jerusalem Guy, Liu Jennifer E, Magalhães Andreia, Marwick Thomas, Sanchez Liza Y, Sicari Rosa, Villarraga Hector R, Lancellotti Patrizio
  
  
  
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• Non-invasive assessment of pulse wave velocity in mice by means of ultrasound images.
  Atherosclerosis

  2014 Nov;237(1):31-7. doi: 10.1016/j.atherosclerosis.2014.08.033.
  
  Di Lascio Nicole, Stea Francesco, Kusmic Claudia, Sicari Rosa, Faita Francesco
  
  Abstract
  
  OBJECTIVE:
  Pulse wave velocity (PWV) is considered as a surrogate marker of arterial stiffness and could be useful for characterizing cardiovascular disease progression even in mouse models. Aim of this study was to develop an image process algorithm for assessing arterial PWV in mice using ultrasound images only and test it on the evaluation of age-associated differences in abdominal aorta PWV.
  
  METHODS:
  Ultrasound scans were obtained from ten adult (mean age: 5.5 months) and nine old (mean age: 15.5 months) wild type male mice (strain C57BL6) under gaseous anesthesia. For each mouse, instantaneous values of diameter and flow velocity were obtained from abdominal aorta B-mode and PW-Doppler, respectively. Single-beat mean diameter and velocity were calculated providing the velocity-diameter (lnD-V) loop. PWV values for both the early systolic phase (aaPWV) and the late systolic one (aaPWVls) were obtained from the slope of the corresponding linear parts of the loop. Relative distension (relD) was calculated from the mean diameter signal.
  
  RESULTS:
  aaPWV values for adult mice (1.91 ± 0.44 m/s) were significantly lower (p 
  CONCLUSIONS:
  The proposed system discriminates well between age groups and supplies a non-invasive evaluation of anatomical and functional parameters of the mouse abdominal aorta. Since it provides a non-invasive PWV assessment from ultrasound (US) images only, it may offer a simple and useful system for evaluation of local vascular stiffness at other arterial site in the mouse, such as the carotid artery.
  
  Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
  
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• Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
  J Am Soc Echocardiogr

  2014 Sep;27(9):911-39. doi: 10.1016/j.echo.2014.07.012.
  
  Plana Juan Carlos, Galderisi Maurizio, Barac Ana, Ewer Michael S, Ky Bonnie, Scherrer-Crosbie Marielle, Ganame Javier, Sebag Igal A, Agler Deborah A, Badano Luigi P, Banchs Jose, Cardinale Daniela, Carver Joseph, Cerqueira Manuel, DeCara Jeanne M, Edvardsen Thor, Flamm Scott D, Force Thomas, Griffin Brian P, Jerusalem Guy, Liu Jennifer E, Magalhães Andreia, Marwick Thomas, Sanchez Liza Y, Sicari Rosa, Villarraga Hector R, Lancellotti Patrizio
  
  
  
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• [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological surveillance in areas with environmental pollution by natural or anthropogenic arsenic].
  Epidemiol Prev

  2014 ;38(3-4 Suppl 1):27-94.
  
  Bustaffa Elisa, Minichilli Fabrizio, Andreassi Maria Grazia, Carone Simona, Coi Alessio, Cori Liliana, Faita Francesca, Faita Francesco, Grecchi Sabina, Minoia Claudio, Ronchi Anna, Scovassi Ivana, Sicari Rosa, Stea Francesco, Bianchi Fabrizio,
  
  Abstract
  
  INTRODUCTION:
  Arsenic and its inorganic compounds are classified as carcinogenic to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated with both carcinogenic and non-carcinogenic effects. The risk assessment of exposures to low-moderate levels of environmental arsenic (As) is a challenging objective for research and public health. The SEpiAs study, funded by the Italian Ministry of Health (CCM), was carried out in four areas with arsenic pollution prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin, Taranto and Gela.
  
  MATERIALS AND METHODS:
  271 subjects (132 men) aged 20-44, were randomly sampled stratifying by area, gender and age classes. Individual data on residential history, socio-economic status, environmental and occupational exposures, lifestyle and dietary habits, were collected through interviews using questionnaire. In urine samples of recruited subjects, the concentration of inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using inductively coupled mass spectrometer (DRCICP- MS), after chromatographic separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as markers of cardiovascular risk were measured The distributions of iAs and iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles and standard deviation (SD). The associations between As species and variables collected by questionnaire were evaluated by multiple regression analysis.
  
  RESULTS:
  Results showed a high variability of As species within and among areas. Gela and Taranto samples showed higher iAs concentration compared to Viterbo and Amiata. Subjects with iAs>1,5 ?g/L or iAs+MMA+DMA>15 ?g/L (thresholds suggested by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%), respectively. A positive association between iAs and use of drinking water emerged in the Viterbo sample, between iAs and occupational exposure in the Gela and Taranto samples. Fish consumption was associated with higher iAs concentration in the whole sample, and particularly in men of the Gela sample. Similar results were observed for iAs+MMA+DMA. Subjects with iAs or iAs+MMA+DMA values higher than the 95th percentile were 15 (6Taranto, 5 Gela, 3Viterbo, 1 Amiata). The relationships between iAs and organic species (methylation efficiency ratios) were different between sex in the four areas. The relevance of polymorphisms AS3MT Met287Thr, GST-T1, GST-M1, OGG1 was confirmed. The analysis of carotid intima-media-thickness showed normal values, but higher among man of Viterbo, Taranto and Gela areas.
  
  CONCLUSIONS:
  Results are informative of exposure to inorganic and organic As in large or at least non-negligible quotas of the samples. The SEpiAs results suggest a further deepening on routes of exposure to arsenic species, and support the recommendation to implement primary prevention measures to reduce population exposure.
  
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• Left atrial dysfunction detected by speckle tracking in patients with systemic sclerosis.
  Cardiovasc Ultrasound

  2014 Aug;12():30. doi: 10.1186/1476-7120-12-30.
  
  Agoston Gergely, Gargani Luna, Miglioranza Marcelo Haertel, Caputo Maria, Badano Luigi Paolo, Moreo Antonella, Muraru Denisa, Mondillo Sergio, Moggi Pignone Alberto, Matucci Cerinic Marco, Sicari Rosa, Picano Eugenio, Varga Albert
  
  Abstract
  
  BACKGROUND:
  Cardiac involvement is a relevant clinical finding in systemic sclerosis (SSc) and is associated with poor prognosis. Left atrial (LA) remodeling and/or dysfunction can be an early sign of diastolic dysfunction. Two-dimensional speckle tracking echocardiography (STE) is a novel and promising tool for detecting very early changes in LA myocardial performance.
  
  AIM:
  To assess whether STE strain parameters may detect early alterations in LA function in SSc patients.
  
  METHODS:
  Forty-two SSc patients (Group 1, age 50?±?14 years, 95% females) without clinical evidence for cardiac involvement and 42 age- and gender-matched control subjects (Group 2, age 49?±?13 years, 95% females) were evaluated with comprehensive 2D and Doppler echocardiography, including tissue Doppler imaging analysis. Positive peak left atrial longitudinal strain (? pos peak), second positive left atrial longitudinal strain (sec ? pos peak), and negative left atrial longitudinal strain (? neg peak) were measured using a 12-segment model for the LA, by commercially available semi-automated 2D speckle-tracking software (EchoPac PC version 108.1.4, GE Healthcare, Horten, Norway).
  
  RESULTS:
  All SSc patients had a normal left ventricular ejection fraction (63.1?±?4%). SSc patients did not differ from controls in E/A (Group 1?=?1.1?±?0.4 vs Group 2?=?1.3?±?0.4, p?=?.14) or pulmonary arterial systolic pressure (Group 1?=?24.1?±?8 mmHg vs Group 2?=?21?±?7 mmHg, p?=?.17). SSc patients did not show significantly different indexed LA volumes (Group 1?=?24.9?±?5.3 ml/m2 vs Group 2?=?24.7?±?4.4 ml/m2, p?=?.8), whereas E/e' ratio was significantly higher in SSc (Group 1?=?7.6?±?2.4 vs Group 2?=?6.5?±?1.7, p
  CONCLUSION:
  2D speckle-tracking echocardiography is a sensitive tool to assess impairment of LA mechanics, which is detectable in absence of changes in LA size and volume, and may represent an early sign of cardiac involvement in patients with SSc.
  
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• Focus cardiac ultrasound: the European Association of Cardiovascular Imaging viewpoint.
  Eur Heart J Cardiovasc Imaging

  2014 Sep;15(9):956-60. doi: 10.1093/ehjci/jeu081.
  
  Neskovic Aleksandar N, Edvardsen Thor, Galderisi Maurizio, Garbi Madalina, Gullace Giuseppe, Jurcut Ruxandra, Dalen Havard, Hagendorff Andreas, Lancellotti Patrizio, , Popescu Bogdan A, Sicari Rosa, Stefanidis Alexander
  
  Abstract
  
  The concept of point-of-care, problem-oriented focus cardiac ultrasound examination (FoCUS) is increasingly applied in the settings of medical emergencies, including cardiac diseases. The European Association of Cardiovascular Imaging (EACVI) recognizes that cardiologists are not the only medical professionals dealing with cardiovascular emergencies. In reality, emergency cardiac diagnostics and treatment are also carried out by a wide range of specialists. For the benefit of the patients, the EACVI encourages any medical professional, sufficiently trained to obtain valuable information from FoCUS, to use it in emergency settings. These medical professionals need to have the necessary knowledge to understand the obtained information entirely, and to use it correctly, thoughtfully and with care. In this document, the EACVI underlines major differences between echocardiography and FoCUS, and underscores the need for specific education and training in order to fully utilize advantages and minimize drawbacks of this type of cardiac ultrasound examination in the critically ill patients.
  
  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: Journals.permissions@oup.com.
  
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• Cardiac calcification at transthoracic echocardiography predicts stress echo results: a multicentre study.
  Int J Cardiol

  2014 Jun;174(2):393-5. doi: 10.1016/j.ijcard.2014.04.007.
  
  Gaibazzi Nicola, Sicari Rosa, Agricola Eustachio, Cioffi Giovanni, Mazzone Carmine, Albertini Lisa, Faden Giacomo, Molinaro Sabrina, Regazzoli Damiano, Di Lenarda Andrea, Faggiano Pompilio
  
  
  
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• Prognostic meaning of coronary microvascular disease in type 2 diabetes mellitus: a transthoracic Doppler echocardiographic study.
  J Am Soc Echocardiogr

  2014 Jul;27(7):742-8. doi: 10.1016/j.echo.2014.02.010.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Bovenzi Francesco, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  The prognostic value of Doppler-derived coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery in patients with type 2 diabetes with preserved left ventricular systolic function and without flow-limiting stenoses on angiography remains undetermined.
  
  METHODS:
  The study sample consisted of 144 patients with type 2 diabetes (82 men; mean age 62 ± 10 years) with chest pain or angina-equivalent symptoms, no histories of coronary artery disease, and echocardiographic ejection fractions ? 50%. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler echocardiography and coronary angiography showing normal coronary arteries or nonobstructive coronary artery disease.
  
  RESULTS:
  Mean CFVR was 2.44 ± 0.57. On individual patient analysis, 109 patients (76%) had CFVR > 2, and 35 (24%) had CFVR ? 2. During a median follow-up period of 29 months (interquartile range, 14-44 months), 17 hard events (five deaths, 12 nonfatal myocardial infarctions) occurred. The annual hard-event rate was 13.9% in subjects with CFVR ? 2 and 2.0% in those with CFVR > 2. The annual event rate associated with CFVR ? 2 was significantly higher both in patients with left ventricular hypertrophy (P
  CONCLUSIONS:
  Microvascular dysfunction before the occurrence of coronary artery involvement is a strong and independent predictor of outcomes in patients with type 2 diabetes. Vasodilator stress CFVR is a suitable tool to assess microvascular dysfunction in routine clinical practice.
  
  Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.
  
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• Preserved contractile reserve in a dobutamine test for the prediction of a response to resynchronisation therapy in ischaemic and non-ischaemic cardiomyopathy--a multicenter ViaCRT study.
  Int J Cardiol

  2014 Mar;172(2):476-7. doi: 10.1016/j.ijcard.2013.12.204.
  
  Mizia-Stec Katarzyna, Wita Krystian, Mizia Magdalena, Szwed Hanna, Nowalany-Kozielska Ewa, Chrzanowski ?ukasz, ?oboz-Grudzie? Krystyna, Gackowski Andrzej, Gilewski Wojciech, Chmiel Artur, Sicari Rosa, P?o?ska-Go?ciniak Edyta
  
  
  
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• The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology.
  Eur Heart J

  2014 Mar;35(10):665-72. doi: 10.1093/eurheartj/eht394.
  
  Picano Eugenio, Vañó Eliseo, Rehani Madan M, Cuocolo Alberto, Mont Lluis, Bodi Vicente, Bar Olivier, Maccia Carlo, Pierard Luc, Sicari Rosa, Plein Sven, Mahrholdt Heiko, Lancellotti Patrizio, Knuuti Juhani, Heidbuchel Hein, Di Mario Carlo, Badano Luigi P
  
  Abstract
  
  The benefits of cardiac imaging are immense, and modern medicine requires the extensive and versatile use of a variety of cardiac imaging techniques. Cardiologists are responsible for a large part of the radiation exposures every person gets per year from all medical sources. Therefore, they have a particular responsibility to avoid unjustified and non-optimized use of radiation, but sometimes are imperfectly aware of the radiological dose of the examination they prescribe or practice. This position paper aims to summarize the current knowledge on radiation effective doses (and risks) related to cardiac imaging procedures. We have reviewed the literature on radiation doses, which can range from the equivalent of 1-60 milliSievert (mSv) around a reference dose average of 15 mSv (corresponding to 750 chest X-rays) for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multidetector coronary angiography, or a myocardial perfusion imaging scintigraphy. We provide a European perspective on the best way to play an active role in implementing into clinical practice the key principle of radiation protection that: 'each patient should get the right imaging exam, at the right time, with the right radiation dose'.
  
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• Determining optimal noninvasive parameters for the prediction of left ventricular remodeling in chronic ischemic patients.
  Scand Cardiovasc J

  2013 Dec;47(6):329-34. doi: 10.3109/14017431.2013.857039.
  
  Rademakers Frank, Engvall Jan, Edvardsen Thor, Monaghan Mark, Sicari Rosa, Nagel Eike, Zamorano José, Ukkonen Heikki, Ebbers Tino, Di Bello Vitantonio, Voigt Jens-Uwe, Herbots Lieven, Claus Piet, D'hooge Jan
  
  Abstract
  
  OBJECTIVES:
  DOPPLER-CIP aims to determine the optimal noninvasive parameters (myocardial function, perfusion, ventricular blood flow, cell integrity) and methodology (ergometry, echocardiography, scintigraphy, MRI) in a given ischemic substrate that best predicts the impact of an intervention (or the lack thereof) on adverse morphological ventricular remodeling and functional recovery. Moreover, the relative predictive value of each of these parameters, in respect to the cost of extracting this information in order to enable optimization of cost-effectiveness for improved health care, will be determined by this project.
  
  DESIGN:
  DOPPLER-CIP is a multi-center registry study. All patients with ischemic heart disease included in this study undergo at least two noninvasive stress imaging examinations at baseline. The presence/or absence of left ventricular (LV) remodeling will be assessed after a follow-up of 2 years, during which all cardiac events will be registered.
  
  RESULTS:
  676 patients were included. Currently, baseline data analysis is almost finished and the follow-up is ongoing.
  
  CONCLUSIONS:
  After completion, DOPPLER-CIP will provide evidence-based guidelines toward the most effective use of cardiac imaging in the chronically ischemic heart disease patient. The study will generate information, knowledge, and insight into the new imaging methodologies and into the pathophysiology of chronic ischemic heart disease.
  
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• RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study.
  JACC Cardiovasc Imaging

  2013 Dec;6(12):1287-97. doi: 10.1016/j.jcmg.2013.08.007.
  
  Pratali Lorenza, Allemann Yves, Rimoldi Stefano F, Faita Francesco, Hutter Damian, Rexhaj Emrush, Brenner Roman, Bailey Damian M, Sartori Claudio, Salmon Carlos Salinas, Villena Mercedes, Scherrer Urs, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers.
  
  BACKGROUND:
  CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension.
  
  METHODS:
  In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography.
  
  RESULTS:
  Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p 
  CONCLUSIONS:
  Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).
  
  Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Effect of concomitant oral chronic dipyridamole therapy on inflammatory cytokines in heart failure patients.
  Clin Lab

  2013 ;59(7-8):843-9.
  
  Del Ry Silvia, Morales Maria Aurora, Scali Maria Chiara, Tafi Alessandro, Giustarini Carlo, Posteraro Federico, Ambrosini Vittorio, Agrusta Marco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  To assess whether dipyridamole therapy exerts a significant anti-inflammatory effect in heart failure patients.
  
  METHODS:
  We performed a retrospective analysis of the stored bio-samples of 3 groups of patients: 1) 25 normal healthy controls (N); 2) 25 heart failure patients (HF) under standard optimal therapy, including aspirin; 3) 17 HF patients with previous stroke and under clinically-driven therapy with A (Aggrenox, long-acting dipyridamole 200 mg + aspirin 25 mg, twice daily) for at least 1 month (HF-A). In all, we evaluated interleukin (IL)-6, adiponectin and C-reactive protein (CRP) as well as NT-proBNP. The same laboratory measurements were performed in the 17 HF patients with recent or previous stroke, both before and 1-month after clinically driven administration of A.
  
  RESULTS:
  All laboratory inflammatory indices were significantly higher in HF patients compared to N: IL-6 (N = 0.68 (0.3 - 12.7) vs. HF = 3.10 (0.5 - 16.7) vs. HF-A = 1.24 (0.3 - 3.3) pg/mL; p
  CONCLUSIONS:
  HF patients show an increase in inflammatory indices independently of underlying A therapy.
  
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• Lung ultrasound for the evaluation of pulmonary congestion in outpatients: a comparison with clinical assessment, natriuretic peptides, and echocardiography.
  JACC Cardiovasc Imaging

  2013 Nov;6(11):1141-51. doi: 10.1016/j.jcmg.2013.08.004.
  
  Miglioranza Marcelo Haertel, Gargani Luna, Sant'Anna Roberto Tofani, Rover Marciane Maria, Martins Vitor Magnus, Mantovani Augusto, Weber Cristina, Moraes Maria Antonieta, Feldman Carlos Jader, Kalil Renato Abdala Karam, Sicari Rosa, Picano Eugenio, Leiria Tiago Luiz Luz
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to define the performance of lung ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and echocardiography, to evaluate decompensation in patients with systolic heart failure (HF) in an outpatient clinic.
  
  BACKGROUND:
  Evaluation of pulmonary congestion in chronic HF is challenging. LUS has been recently proposed as a reliable tool for the semiquantification of extravascular lung water through assessment of B-lines.
  
  METHODS:
  This was a cohort study of patients with moderate to severe systolic HF. Receiver-operating characteristic (ROC) analyses were performed to compare LUS with a previously validated clinical congestion score (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e' ratio, chest x-ray, and 6-min walk test.
  
  RESULTS:
  Ninety-seven patients were enrolled. Decompensation was present in 57.7% of patients when estimated by CCS, 68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' ?15. The number of B-lines was correlated to NT-proBNP (r = 0.72; p 1,000 pg/ml), LUS yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing the best accuracy with a cutoff ? 15 B-lines (sensitivity 85%, specificity 83%). A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk test in different combinations as reference for decompensation also corroborated this cutoff and found a similar accuracy for LUS.
  
  CONCLUSIONS:
  In an HF outpatient clinic, B-lines were significantly correlated with more established parameters of decompensation. A B-line ?15 cutoff could be considered for a quick and reliable assessment of decompensation in outpatients with HF.
  
  Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European Renal and Cardiovascular Medicine registry.
  Nephrol Dial Transplant

  2014 Feb;29(2):232-9. doi: 10.1093/ndt/gft309.
  
  Boutouyrie Pierre, Fliser Danilo, Goldsmith David, Covic Adrian, Wiecek Andrzej, Ortiz Alberto, Martinez-Castelao Alberto, Lindholm Bengt, Massy Ziad A, Suleymanlar Gultekin, Sicari Rosa, Gargani Luna, Parati Gianfranco, Mallamaci Francesca, Zoccali Carmine, London Gerard M
  
  Abstract
  
  Epidemiological studies have highlighted the role of arterial stiffness as a risk factor for development of cardiovascular (CV) diseases. Moreover, aortic stiffness has been shown to be a significant predictive factor of all-cause and CV mortality in different populations including patients with end-stage renal disease. Pulse-wave velocity (PWV) is the most widely used technique to assess arterial stiffness. Although PWV can be measured on any artery or between any arterial sites, only carotid-to-femoral PWV, representing stiffness of the aorta and iliofemoral axes, has been shown to have predictive value for morbidity and mortality. The several available commercial devices differ according to the type of signal (pressure, distension, flow) or by recording both sites simultaneously or using ECG synchronization. It is also possible to directly measure arterial diameter changes during the cardiac cycle and link them to local pulse-pressure changes, which provides the pressure-diameter relationship and stress-strain relationship if arterial wall thickness is also measured. These techniques are based on high-precision vascular echo tracking or magnetic resonance imaging and applanation tonometry. This paper summarizes the basic principles of arterial haemodynamics and various methodologies to assess stiffness and the latest consensus recommendations for clinical applications.
  
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• End-systolic elastance and ventricular-arterial coupling reserve predict cardiac events in patients with negative stress echocardiography.
  Biomed Res Int

  2013 ;2013():235194. doi: 235194.
  
  Bombardini Tonino, Costantino Marco Fabio, Sicari Rosa, Ciampi Quirino, Pratali Lorenza, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography.
  
  METHODS:
  We enrolled 891 patients (593 males mean age 63 ± 12, ejection fraction 48 ± 17%), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (E(LV)I), ventricular arterial coupling (VAC) indexed by the ratio of the E(LV)I to arterial elastance index (E aI), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization.
  
  RESULTS:
  During a median followup of 19 months (interquartile range 8-36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors E(LV)I reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole.
  
  CONCLUSIONS:
  Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of E(LV)I reserve and VAC reserve during stress echo.
  
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• Cardiovascular effects of arsenic: clinical and epidemiological findings.
  Environ Sci Pollut Res Int

  2014 Jan;21(1):244-51. doi: 10.1007/s11356-013-2113-z.
  
  Stea Francesco, Bianchi Fabrizio, Cori Liliana, Sicari Rosa
  
  Abstract
  
  Several population studies relate exposure to high levels of arsenic with an increased incidence of ischemic heart disease and cardiovascular mortality. An association has been shown between exposure to high levels of arsenic and cardiovascular risk factors such as hypertension and diabetes mellitus, and vascular damage such as subclinical carotid atherosclerosis. The mechanisms underlying these phenomena are currently being studied and appear to indicate an alteration of vascular function. However, the effects of low levels of exposure to arsenic and their potential detrimental cardiovascular effect are less explored. The article provides an overview of the pathophysiologic mechanisms linking low-level arsenic exposure to the occurrence of cardiovascular disease and its complications, and some potential preventive strategies to implement.
  
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• Transplant of stunned donor hearts rescued by pharmacological stress echocardiography: a "proof of concept" report.
  Cardiovasc Ultrasound

  2013 Aug;11():27. doi: 10.1186/1476-7120-11-27.
  
  Bombardini Tonino, Gherardi Sonia, Leone Ornella, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  Due to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Hearts with regional or global left ventricular dysfunction are excluded from donation, but stress echo might be useful to identify patients with reversible wall motion abnormalities, potentially eligible for donation.
  
  METHODS:
  Six marginal candidate donors (mean age, 40 ± 13 years; three men) were enrolled. Resting echocardiography showed in all subjects a LV ejection fraction ? 45% (mean 51 ± 5%), but multiple risk factors were present. All donors had either global or discrete wall motion abnormalities: Wall Motion Score Index (WMSI) rest = 1.33 ± 0.25. Stress echocardiography was performed with the dipyridamole high dose of 0.84 mg/kg given over 6 min.
  
  RESULTS:
  The stress echo results were abnormal in three donors (WMSI rest = 1.51 ± 0.19 vs peak = 1.41 ± 0.30). These hearts were excluded from donation and cardiac pathology verification was available in two cases of confirmed LV myocardial fibrosis and/or severe coronary stenosis. The remaining three hearts improved during stress (WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06) and were transplanted uneventfully. Recipients (three males, mean age 53 ± 4 years) underwent post-TX coronary angiography, IVUS and endomyocardial biopsies. No recipient had primary graft failure, and all showed normal coronary angiography and normal LV function (EF = 57 ± 6%; WMSI = 1 ± 0) at 1-month post-TX. The recipients were alive at 12-month median follow-up.
  
  CONCLUSIONS:
  Dipyridamole stress echo performed in brain-dead potential donors with LV resting global or discrete wall motion abnormalities identifies hearts with severe morphologic abnormalities excluded from donation (with fixed response during stress echo) from hearts eligible for donation, showing improvement in regional wall motion during stress (viability response) and normal function and coronary anatomy following transplantation.
  
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• Ectopic fat: the true culprit linking obesity and cardiovascular disease?
  Thromb Haemost

  2013 Oct;110(4):651-60. doi: 10.1160/TH13-04-0285.
  
  Morelli Mariangela, Gaggini Melania, Daniele Giuseppe, Marraccini Paolo, Sicari Rosa, Gastaldelli Amalia
  
  Abstract
  
  Obesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardio-metabolic diseases.
  
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• Non-cancer atherosclerotic effects associated with environmental and therapeutic radiation doses: the Chernobyl thyroid cancer children study.
  Int J Cardiol

  2013 Oct;168(4):4255-7. doi: 10.1016/j.ijcard.2013.04.161.
  
  Bruno Rosa Maria, Sicari Rosa, Corciu Anca Irina, Bianchini Elisabetta, Faita Francesco, Di Stefano Rossella, Antonelli Alessandro, Ghiadoni Lorenzo, Picano Eugenio
  
  
  
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• The incremental diagnostic value of coronary flow reserve and left ventricular elastance during high-dose dipyridamole stress echocardiography in patients with normal wall motion at rest.
  Int J Cardiol

  2013 Sep;168(2):1683-4. doi: 10.1016/j.ijcard.2013.03.076.
  
  Bombardini Tonino, Gherardi Sonia, Marraccini Paolo, Schlueter Mathis Christian, Sicari Rosa, Picano Eugenio
  
  
  
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• Imaging cardiac fat.
  Eur Heart J Cardiovasc Imaging

  2013 Jul;14(7):625-30. doi: 10.1093/ehjci/jet045.
  
  Davidovich Daniel, Gastaldelli Amalia, Sicari Rosa
  
  Abstract
  
  Ectopic fat deposition has been associated with lipotoxicity and derangement in local and systemic metabolism, insulin resistance, cardiac dysfunction, atherosclerosis, local, and systemic inflammation. The mechanisms and potentially detrimental effects of such an accumulation should be fully investigated in order to establish preventive strategies. The aim of this review is to provide an overview of current knowledge regarding imaging techniques to measure cardiac fat deposition and its potential clinical relevance, if any.
  
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• Pulmonary congestion predicts cardiac events and mortality in ESRD.
  J Am Soc Nephrol

  2013 Mar;24(4):639-46. doi: 10.1681/ASN.2012100990.
  
  Zoccali Carmine, Torino Claudia, Tripepi Rocco, Tripepi Giovanni, D'Arrigo Graziella, Postorino Maurizio, Gargani Luna, Sicari Rosa, Picano Eugenio, Mallamaci Francesca,
  
  Abstract
  
  Pulmonary congestion is highly prevalent and often asymptomatic among patients with ESRD treated with hemodialysis, but whether its presence predicts clinical outcomes is unknown. Here, we tested the prognostic value of extravascular lung water measured by a simple, well validated ultrasound B-lines score (BL-US) in a multicenter study that enrolled 392 hemodialysis patients. We detected moderate-to-severe lung congestion in 45% and very severe congestion in 14% of the patients. Among those patients with moderate-to-severe lung congestion, 71% were asymptomatic or presented slight symptoms of heart failure. Compared with those patients having mild or no congestion, patients with very severe congestion had a 4.2-fold risk of death (HR=4.20, 95% CI=2.45-7.23) and a 3.2-fold risk of cardiac events (HR=3.20, 95% CI=1.75-5.88) adjusted for NYHA class and other risk factors. Including the degree of pulmonary congestion in the model significantly improved the risk reclassification for cardiac events by 10% (P
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• EuroEcho and other imaging modalities: highlights.
  Eur Heart J Cardiovasc Imaging

  2013 Mar;14(3):195-200. doi: 10.1093/ehjci/jet007.
  
  Lancellotti Patrizio, Magne Julien, Sicari Rosa, Kitsiou Anastasia, Frank Herbert, Miller Owen, Badano Luigi P
  
  Abstract
  
  The annual meeting of the European Association of Echocardiography (Euroecho and other Imaging Modalities) was held in Athens, Greece. In the present paper, we present a summary of the 'Highlights' session.
  
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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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• 2013 European Association cardiovascular imaging research grants.
  Eur Heart J Cardiovasc Imaging

  2013 Mar;14(3):294. doi: 10.1093/ehjci/jes318.
  
  Sicari Rosa, Edvardsen Thor, Badano Luigi, Lancellotti Patrizio, Habib Gilbert, Maurer Gerald
  
  
  
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• Stress echocardiography for risk assessment in octogenarians.
  Int J Cardiol

  2013 Sep;167(5):2356-8. doi: 10.1016/j.ijcard.2012.11.044.
  
  Cortigiani Lauro, Bigi Riccardo, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  
  
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• Insulin resistance and endothelial dysfunction: a mutual relationship in cardiometabolic risk.
  Curr Pharm Des

  2013 ;19(13):2420-31.
  
  Del Turco Serena, Gaggini Melania, Daniele Giuseppe, Basta Giuseppina, Folli Franco, Sicari Rosa, Gastaldelli Amalia
  
  Abstract
  
  Cardiometabolic risk comprises a cluster of traditional and emerging factors that are good indicators of a patient's overall risk for type 2 diabetes and cardiovascular disease. The insulin resistance, a key feature common to obesity and type 2 diabetes, is associated with impaired vascular response and contributes to increased cardiovascular risk. Abnormal vascular insulin signalling induces endothelial dysfunction, the initial step of atherosclerotic process, characterized by attenuated nitric oxide-mediated vasodilatation and atherogenic response. Insulin resistance and endothelial dysfunction are two pathological conditions that can co-exist, even if their cause-effect relationship is not yet clarified. Multiple signaling pathways shared by insulin resistance and endothelial dysfunction include hyperinsulinemia, glucotoxicity, lipotoxicity, and inflammation. These mechanisms selectively impair PI3K-dependent insulin in vascular endothelium harming endothelial balance and strengthening the evidence of the close association between metabolic and cardiovascular disease. The present review analyzes the close relationship between endothelial dysfunction and insulin resistance and explores the common mechanisms, with clinical considerations and pharmacological strategies.
  
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• Pulmonary hypertension in CKD.
  Am J Kidney Dis

  2013 Apr;61(4):612-22. doi: 10.1053/j.ajkd.2012.07.029.
  
  Bolignano Davide, Rastelli Stefania, Agarwal Rajiv, Fliser Danilo, Massy Ziad, Ortiz Alberto, Wiecek Andrzej, Martinez-Castelao Alberto, Covic Adrian, Goldsmith David, Suleymanlar Gultekin, Lindholm Bengt, Parati Gianfranco, Sicari Rosa, Gargani Luna, Mallamaci Francesca, London Gerard, Zoccali Carmine
  
  Abstract
  
  Pulmonary arterial hypertension is a rare disease often associated with positive antinuclear antibody and high mortality. Pulmonary hypertension, which rarely is severe, occurs frequently in patients with chronic kidney disease (CKD). The prevalence of pulmonary hypertension ranges from 9%-39% in individuals with stage 5 CKD, 18.8%-68.8% in hemodialysis patients, and 0%-42% in patients on peritoneal dialysis therapy. No epidemiologic data are available yet for earlier stages of CKD. Pulmonary hypertension in patients with CKD may be induced and/or aggravated by left ventricular disorders and risk factors typical of CKD, including volume overload, an arteriovenous fistula, sleep-disordered breathing, exposure to dialysis membranes, endothelial dysfunction, vascular calcification and stiffening, and severe anemia. No specific intervention trial aimed at reducing pulmonary hypertension in patients with CKD has been performed to date. Correcting volume overload and treating left ventricular disorders are factors of paramount importance for relieving pulmonary hypertension in patients with CKD. Preventing pulmonary hypertension in this population is crucial because even kidney transplantation may not reverse the high mortality associated with established pulmonary hypertension.
  
  Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
  
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• Coronary flow reserve during dipyridamole stress echocardiography predicts mortality.
  JACC Cardiovasc Imaging

  2012 Nov;5(11):1079-85. doi: 10.1016/j.jcmg.2012.08.007.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Bovenzi Francesco, Molinaro Sabrina, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  OBJECTIVES:
  The goal of this study was to evaluate the ability of coronary flow reserve (CFR) over regional wall motion to predict mortality in patients with known or suspected coronary artery disease (CAD).
  
  BACKGROUND:
  CFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography.
  
  METHODS:
  In a prospective, multicenter, observational study, we evaluated 4,313 patients (2,532 men; mean age 65 ± 11 years) with known (n = 1,547) or suspected (n = 2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFR evaluation of left coronary descending artery (LAD) by Doppler. Overall mortality was the only endpoint analyzed.
  
  RESULTS:
  Stress echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was 2.35 ± 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR ?2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36), 146 patients died. The 4-year mortality was markedly higher in subjects with CFR ?2 than in those with CFR >2, both considering the group with ischemia (39% vs. 7%; p
  CONCLUSIONS:
  CFR on LAD is a strong and independent indicator of mortality, conferring additional prognostic value over wall motion analysis in patients with known or suspected CAD. A negative result on stress echocardiography with a normal CFR confers an annual risk of death
  Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• [The STICH Viability substudy].
  G Ital Cardiol (Rome)

  2012 Nov;13(11):705-9. doi: 10.1714/1168.12945.
  
  Menicanti Lorenzo, Sicari Rosa
  
  
  
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• The use of echocardiography in observational clinical trials: the EURECA-m registry.
  Nephrol Dial Transplant

  2013 Jan;28(1):19-23. doi: 10.1093/ndt/gfs399.
  
  Sicari Rosa, Gargani Luna, Wiecek Andrzej, Covic Adrian, Goldsmith David, Suleymanlar Gultekin, Parati Gianfranco, Ortiz Alberto, Massy Ziad, Martinez-Castelao Alberto, Lindholm Bengt, Heine Gunnar H, Fliser Danilo, Mallamaci Francesca, London Gerard, Zoccali Carmine,
  
  Abstract
  
  Echocardiography is the most widely used non-invasive imaging technique due to its availability, low cost, transportability and lack of ionizing radiations. However, it suffers from the main limitation of being highly subjective and operator-dependent. Furthermore, specifically, population or disease-dependent issues exist which should be addressed when this technique is applied in multicenter studies. As to the population of patients with end-stage renal disease (ESRD) maintained on chronic dialysis, indexation of echocardiographic parameters and timing of echocardiography in relationship to dialysis represent a specific, main issue that needs to be carefully considered and standardized. Scientific societies recommend the set-up of core laboratories in order to reduce inter- and intra-observer variability when an echocardiographic parameter is considered as an end-point in clinical research. Several studies have shown the superiority of interpretation given by echocardiography core-lab reading. These advantages are counterbalanced by higher costs and complexity. The EURECA-m registry by the EURECA-m working group, an ERA-EDTA initiative, aimed at promoting the scientific collaboration among professionals in the field of cardiovascular and renal medicine. The registry involves several centers in Europe and one of its aims is to measure conventional echocardiographic parameters in ESRD patients on chronic dialysis. A central reading protocol has been set up for the registry in order to give robustness to the echo studies.
  
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• The role of cardiac fat in insulin resistance.
  Curr Opin Clin Nutr Metab Care

  2012 Nov;15(6):523-8. doi: 10.1097/MCO.0b013e328358be7b.
  
  Gastaldelli Amalia, Morales Maria A, Marraccini Paolo, Sicari Rosa
  
  Abstract
  
  PURPOSE OF REVIEW:
  To evaluate the relationship between cardiac fat accumulation and insulin resistance. We discuss the current knowledge regarding the different techniques for measuring, in vivo in humans, cardiac fat deposition, the effects of systemic and myocardial insulin resistance and the clinical relevance of the relation between atherosclerosis and cardiac fat in conditions of insulin resistance.
  
  RECENT FINDINGS:
  In humans, fat accumulates mainly around the heart, as epicardial, perivascular and intrathoracic fat, but also inside the cardiomyocytes. All these cardiac fat depots have been shown to be markers of cardiac lipotoxicity, mitochondrial dysfunction, inflammation and local and systemic insulin resistance as well as of atherosclerosis and cardiac dysfunction.
  
  SUMMARY:
  Although cardiac fat is associated with impairment in heart metabolism and cardiac dysfunction, the interplay among cardiac fat accumulation, insulin resistance and cardiac dysfunction remains to be fully established.
  
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• Prognostic implication of Doppler echocardiographic derived coronary flow reserve in patients with left bundle branch block.
  Eur Heart J

  2013 Feb;34(5):364-73. doi: 10.1093/eurheartj/ehs310.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Bovenzi Francesco, Molinaro Sabrina, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  AIMS:
  Myocardial ischaemia during pharmacological stress echocardiography is a strong prognostic predictor in patients with a left bundle branch block (LBBB). However, the additive value of Doppler-derived coronary flow reserve (CFR) during pharmacological stress testing remains to be investigated in this subset of patients.
  
  METHODS AND RESULTS:
  The study group consisted of 324 LBBB patients (187 men; age 68 ± 10 years) with known (n = 74) or suspected (n = 250) coronary artery disease who had undergone dipyridamole (up to 0.84 mg/kg over 6') stress echocardiography with CFR assessment of left anterior descending (LAD) by Doppler. A value of CFR ? 2.0 was considered abnormal. The median duration of follow-up was 15 months (first to third quartile: 8-34 months). Of the 324 patients, 52 (16%) had ischaemia at stress echo by wall motion criteria, and 139 (43%) had a CFR ? 2. During follow-up, 51 (16%) events occurred: 37 deaths and 14 myocardial infarctions (MIs). Age (HR: 1.09, 95% CI: 1.04-1.15, P 2 (49 vs. 6% and 56 vs. 8%, respectively; P
  CONCLUSIONS:
  Abnormal CFR on LAD is a strong and independent indicator of mortality and death or MI in patients with LBBB, and is associated with markedly increased risk also in the subset of patients with stress echo negative for ischaemia on therapy.
  
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• Real time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients.
  Cardiovasc Ultrasound

  2012 Jun;10():27. doi: 10.1186/1476-7120-10-27.
  
  Scali Maria Chiara, Basso Massimiliano, Gandolfo Alfredo, Bombardini Tonino, Bellotti Paolo, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Cardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo.
  
  AIM:
  To assess the feasibility of a comprehensive hemodynamic study with RT-3D echo.
  
  METHODS:
  We enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance (characterizing the distal impedance of the arterial system downstream of the aortic valve); ventricular-arterial coupling (a central determinant of net cardiovascular performance); systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG.
  
  RESULTS:
  A complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility?=?95?%). Standard 2D echo examination was completed in 14.8?±?2.2?min. Acquisition of 3D images required an average time of 5?±?0.9?min (range 3.5-7.5?min) and image analysis was completed in 10.1?±?2.8?min (range 6-12?min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7?±?1.5?mmHg?mL(-1)?m(-2), p
  CONCLUSION:
  RT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables--such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients.
  
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• Tissue Doppler systolic velocity change during dobutamine stress echocardiography predicts contractile reserve and exercise tolerance in patients with heart failure.
  Eur Heart J Cardiovasc Imaging

  2013 Feb;14(2):102-9. doi: 10.1093/ehjci/jes096.
  
  Ciampi Quirino, Pratali Lorenza, Porta Michele Della, Petruzziello Bruno, Manganiello Vincenzo, Villari Bruno, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  AIMS:
  Dobutamine stress echocardiography (DSE) is widely used to evaluate myocardial contractile reserve in patients with heart failure (HF). The aim of the study was to assess the relationship between the tissue Doppler (TD) mitral annulus systolic velocity (Sm) change during DSE, contractile reserve, and aerobic exercise capacity in HF patients.
  
  METHODS AND RESULTS:
  Sixty-four HF patients (age 67 ± 9 years, 58% with an ischaemic aetiology, and a mean value of the ejection fraction 29 ± 7%) underwent high-dose DSE. The mean value of the TD mitral annulus septal-lateral Sm change was analysed at rest and at peak DSE. All patients underwent also the cardiopulmonary exercise test. With a receiver operating characteristic analysis, a value of 2.02 cm/s obtained as a stress-rest difference in a mean value of the peak systolic velocity of the mitral annulus (Sm) was the best value for diagnosing the myocardial contractile reserve [area under the curve 0.69 (95% CI 0.56-0.80), sensitivity 69% (95% CI 54-81), specificity 80% (95% CI 45-97)]. The patient population was divided into two groups: with rest-stress Sm change during DSE ? 2.02 cm/s and with rest-stress Sm change >2.02 cm/s. Patients with Sm rest-stress >2.02 change during DSE, compared with patients with rest-stress change ?2.02, showed a lower incidence of severe diastolic dysfunction at rest (16 vs. 46%, P= 0.039) and lower E/Ea values (11 ± 5 vs. 15 ± 6, P = 0.005), similar ejection fraction at rest but higher ejection fraction at peak DSE (53 ± 14 vs. 41 ± 12%, P = 0.001), better myocardial contractile reserve assessed by a pressure-volume relationship (1.89 ± 2.01 vs. 0.58 ± 1.38 mmHg/mL/m(2), P = 0.004), with a lower end-systolic volume (-46 ± 20 vs. -24 ± 19%, P
  CONCLUSION:
  In patients with HF, the rest-stress variation of mitral annulus systolic velocities during DSE predicts the presence of myocardial contractile reserve and exercise tolerance.
  
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• The impact of aging and atherosclerotic risk factors on transthoracic coronary flow reserve in subjects with normal coronary angiography.
  Cardiovasc Ultrasound

  2012 May;10():20. doi: 10.1186/1476-7120-10-20.
  
  Galderisi Maurizio, Rigo Fausto, Gherardi Sonia, Cortigiani Lauro, Santoro Ciro, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  Age may affect coronary flow reserve (CFR) especially in subjects with atherosclerotic risk factors (ARFs). The aim of this prospective, multicenter, observational study was to determine the effects of aging on CFR in patients with normal epicardial coronary arteries and ARFs. Three-hundred-thirty-five subjects (mean age?=?61?years) with at least one ARF but normal coronary angiography underwent high-dose dipyridamole stress-echo with Doppler evaluation of left anterior descending artery. CFR was calculated as the ratio between hyperemic and resting coronary diastolic peak velocities. Patients were divided in age quartiles. CFR was progressively reduced with aging (1st quartile: 3.01?±?0.69, 4th quartile: 2.39?±?0.49, p?0.001). This was mainly due to a gradual increase of resting velocities (1st quartile?=?26.3?±?6.1?cm/s, 4th quartile?=?30.2?±?6.4?cm/s, p?0.001) while the reduction of hyperemic velocities remained unaffected (1st quartile?=?77.7?±?18.9?cm/s, 4th quartile?=?70.9?±?18.4?cm/s, NS). When age quartiles and ARFs were entered into a regression model, third and fourth age quartile (p?0.0005 and p?0.0001 respectively), left ventricular mass index (p?0.0001), diastolic blood pressure (p?0.001), total cholesterol (p?0.002), fasting blood glucose (p?0.01) and male gender (p?0.05) were independent determinants of CFR in the whole population. Aging reduces coronary flow reserve in patients with angiographically normal coronary arteries due to a gradual increase of resting coronary flow velocity. CFR is also affected by atherosclerotic risk factors and left ventricular hypertrophy.
  
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• Prognostic implication of appropriateness criteria for pharmacologic stress echocardiography performed in an outpatient clinic [corrected].
  Circ Cardiovasc Imaging

  2012 May;5(3):298-305. doi: 10.1161/CIRCIMAGING.111.971242.
  
  Cortigiani Lauro, Bigi Riccardo, Bovenzi Francesco, Molinaro Sabrina, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Although appropriateness criteria for stress echocardiography have been developed to deliver high-quality care, the prognostic impact of these criteria remains undefined. Therefore, we sought to assess the prognostic implication of the American College of Cardiology/American Society of Echocardiography appropriateness criteria for pharmacological stress echo in a cohort of ambulatory patients.
  
  METHODS AND RESULTS:
  The study population consisted of 1552 ambulatory patients who underwent pharmacological (752 dobutamine, 800 dipyridamole) stress echo for the evaluation of known (n=549) or suspected (n=1003) coronary artery disease at a single cardiology center. Patients were followed up for a median of 36 months. Indications were determined for consecutive studies by 2 reviewers and categorized as follows: 984 (63%) patients had appropriate, 145 (9%) uncertain, and 423 (27%) inappropriate indication for stress echo. Ischemia was present in 15% of patients with appropriate, 8% of those with uncertain, and 5% of those with inappropriate indication (P
  CONCLUSIONS:
  Inappropriate indication for pharmacological stress echo is common, being documented in about 1 of 4 patients evaluated in an ambulatory setting, and is associated with lower rate of positive results and better survival as compared with appropriate and uncertain indication.
  
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• [Endothelial dysfunction. An integrated overview of the physiopatologic and diagnostic aspects].
  Recenti Prog Med

  2012 Mar;103(3):109-18. doi: 10.1701/1046.11402.
  
  Del Turco Serena, Bianchini Elisabetta, Bucalo Rita, Basta Giuseppina, Bruno Rosa Maria, Sicari Rosa
  
  Abstract
  
  Endothelial dysfunction is an early alteration in the atherosclerotic process. Cardiovascular risk factors induce endothelial dysfunction, characterized by impaired endothelium-dependent vasodilatation and by new proatherogenic, proinflammatory and prothrombotic properties. It is evident as the study of the endothelium could play a key role in the cardiovascular research and can be an useful tool for risk stratification in primary prevention of cardiovascular disease. An ideal approach for the comprehensive evaluation on endothelial physiopathology would take into account and integrate informations about endothelial biology (activation, injury and regenerative capacity) and endothelial function, so to be correlated with clinical data.
  
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• Monocyte subpopulations and cardiovascular risk in chronic kidney disease.
  Nat Rev Nephrol

  2012 Mar;8(6):362-9. doi: 10.1038/nrneph.2012.41.
  
  Heine Gunnar H, Ortiz Alberto, Massy Ziad A, Lindholm Bengt, Wiecek Andrzej, Martínez-Castelao Alberto, Covic Adrian, Goldsmith David, Süleymanlar Gültekin, London Gérard M, Parati Gianfranco, Sicari Rosa, Zoccali Carmine, Fliser Danilo,
  
  Abstract
  
  Chronic microinflammation and its cellular hallmark, monocyte activation, contribute substantially to the tremendous burden of cardiovascular disease (CVD) in patients with chronic kidney diseases (CKD). Monocyte heterogeneity is widely acknowledged. Cell-surface expression of CD14 and CD16 defines three functionally and phenotypically distinct subsets of monocytes: classical (CD14(++)CD16(-)) monocytes, intermediate (CD14(++)CD16(+)) monocytes, and nonclassical (CD14(+)CD16(++)) monocytes. A growing body of circumstantial evidence suggests that intermediate monocytes, in particular, contribute to the development of atherosclerosis in the general population as well as in patients with CKD. Intermediate monocytes express a unique pattern of chemokine receptors that have been implicated in atherogenesis. Moreover, this subset of monocytes is predisposed to secrete proinflammatory cytokines. Findings from epidemiological studies indicate that numbers of intermediate monocytes increase with worsening renal function, and that high cell counts predict adverse outcomes in patients undergoing dialysis as well as in patients at early stages of CKD. Based on laboratory and clinical data, intermediate monocytes are a promising therapeutic target for CVD in patients with CKD.
  
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• Assessment of carotid elasticity during exercise: a reproducibility study.
  Ultrasound Med Biol

  2012 Feb;38(2):223-30. doi: 10.1016/j.ultrasmedbio.2011.10.023.
  
  Bianchini Elisabetta, Bruno Rosa Maria, Corciu Anca Irina, Faita Francesco, Gemignani Vincenzo, Ghiadoni Lorenzo, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  The study aimed to evaluate the reproducibility of carotid elasticity during exercise. Eighteen healthy volunteers (nine males, age 34 ± 3 years, BMI 22 ± 6 kg/m(2)) underwent maximal exercise testing on a graded semi-supine cycle ergometer in two different sessions 3 days apart. Ultrasound B-mode image sequences of the right common carotid were acquired at different steps and analyzed by an automatic system; pressures were estimated by tonometry. Compliance (CC) and distensibility (DC) were significantly decreased at exercise peak and in the first recovery minute (CC from 1.6 ± 0.8 to 1 ± 0.6 mm^(2)/KPa, DC from 56.2 ± 25.3 to 34.5 ± 20 10^(-3)/KPa, p
  Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
  
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• European Association of Echocardiography: Research Grant Programme.
  Eur Heart J Cardiovasc Imaging

  2012 Jan;13(1):47-50. doi: 10.1093/ejechocard/jer266.
  
  Gargani Luna, Muraru Denisa, Badano Luigi P, Lancellotti Patrizio, Sicari Rosa,
  
  Abstract
  
  The European Society of Cardiology (ESC) offers a variety of grants/fellowships to help young professionals in the field of cardiological training or research activities throughout Europe. The number of grants has significantly increased in recent years with contributions from the Associations, Working Groups and Councils of the ESC. The European Association of Echocardiography (EAE) is a registered branch of the ESC and actively takes part in this initiative. One of the aims of EAE is to promote excellence in research in cardiovascular ultrasound and other imaging modalities in Europe. Therefore, since 2008, the EAE offers a Research Grant Programme to help young doctors to obtain research experience in a high standard academic centre (or similar institution oriented to clinical or pre-clinical research) in an ESC member country other than their own. This programme can be considered as a valorization of the geographical mobility as well as cultural exchanges and professional practice in the field of cardiovascular imaging. The programme has been very successful so far, therefore in 2012 the EAE has increased its offer to two grants of 25,000 euros per annum each.
  
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• Abnormal shortened diastolic time length at increasing heart rates in patients with abnormal exercise-induced increase in pulmonary artery pressure.
  Cardiovasc Ultrasound

  2011 Nov;9():36. doi: 10.1186/1476-7120-9-36.
  
  Bombardini Tonino, Sicari Rosa, Bianchini Elisabetta, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  The degree of pulmonary hypertension is not independently related to the severity of left ventricular systolic dysfunction but is frequently associated with diastolic filling abnormalities. The aim of this study was to assess diastolic times at increasing heart rates in normal and in patients with and without abnormal exercise-induced increase in pulmonary artery pressure (PASP).
  
  METHODS:
  We enrolled 109 patients (78 males, age 62 ± 13 years) referred for exercise stress echocardiography and 16 controls. The PASP was derived from the tricuspid Doppler tracing. A cut-off value of PASP ? 50 mmHg at peak stress was considered as indicative of abnormal increase in PASP. Diastolic times and the diastolic/systolic time ratio were recorded by a precordial cutaneous force sensor based on a linear accelerometer.
  
  RESULTS:
  At baseline, PASP was 30 ± 5 mmHg in patients and 25 ± 4 in controls. At peak stress the PASP was normal in 95 patients (Group 1); 14 patients (Group 2) showed an abnormal increase in PASP (from 35 ± 4 to 62 ± 12 mmHg; P
  CONCLUSION:
  The first and second heart sound vibrations non-invasively monitored by a force sensor are useful for continuously assessing diastolic time during exercise. Exercise-induced abnormal PASP was associated with reduced diastolic time at heart rates beyond 100 beats per minute.
  
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• Is viability still viable after the STICH trial?
  Eur Heart J Cardiovasc Imaging

  2012 Mar;13(3):219-26. doi: 10.1093/ejechocard/jer237.
  
  Cortigiani Lauro, Bigi Riccardo, Sicari Rosa
  
  Abstract
  
  Stunning and hibernation represent two different forms of tissue viability identifiable in acute coronary syndromes and chronic ischaemic cardiomyopathy, respectively. Functional recovery occurs spontaneously with myocardial stunning, while it generally follows revascularization in case of hibernating myocardium. Low-dose dobutamine stress echocardiography is an accurate modality for identifying myocardial stunning and provides important information on ventricular remodelling after both systemic thrombolysis and primary angioplasty. In patients with conservatively treated infarction, the prognostic significance of viability by dobutamine stress echocardiography correlates with residual pump function. Substantial contractile reserve is predictive of favourable outcome in patients with poor but not in those with preserved or slightly reduced left ventricular function. Non-invasive assessment of coronary flow reserve with transthoracic Doppler echocardiography of the left anterior descending coronary artery allows to distinguish between necrotic and stunned myocardium and predicts ventricular remodelling following primary angioplasty. Resting echocardiographic examination can provide information on hibernating myocardium. In particular, systolic thickening
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• Additive value of severe diastolic dysfunction and contractile reserve in the identification of responders to cardiac resynchronization therapy.
  Eur J Heart Fail

  2011 Dec;13(12):1323-30. doi: 10.1093/eurjhf/hfr132.
  
  Ciampi Quirino, Pratali Lorenza, Citro Rodolfo, Villari Bruno, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  AIM:
  The identification of responders remains challenging in cardiac resynchronization therapy (CRT). In this study we assessed the role of myocardial contractile reserve (CR) during dobutamine stress echocardiography (DSE) and resting severe diastolic dysfunction for identifying responders to CRT.
  
  METHODS AND RESULTS:
  Sixty-nine patients (59% with ischaemic aetiology, ejection fraction: 26 ± 5%) referred for CRT underwent high-dose DSE. Contractile reserve was evaluated using a pressure-volume relationship, defined as systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. We defined severe diastolic dysfunction as the presence of restrictive patterns and/or E/E' > 15. We divided the patients into four groups as follows: presence (CR+) or absence (CR-) of myocardial CR and presence (Diast+) or absence (Diast-) of severe diastolic dysfunction. Patients with CR+ Diast- showed higher percentage of clinical responders (91 vs. 46%, P= 0.002) and echocardiographic responders (90 vs. 25%, P= 0.001) to CRT, compared with patients with CR- Diast+. By log-rank analysis, event-free survival was significantly poorer in patients with CR- Diast+ (log rank = 18.36, P= 0.0004).
  
  CONCLUSION:
  Heart failure patients with severe diastolic dysfunction and absence of myocardial CR during DSE had a poorer clinical and echocardiographic response to CRT. The associated evaluations of diastolic function and CR had an additive value in the identification of responders to CRT.
  
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• Maternal and sex dependency of insulin resistance: longitudinal PET and echocardiography study from the healthy fetus to the adult minipig.
  J Nucl Med

  2011 Dec;52(12):1993-2000. doi: 10.2967/jnumed.111.087882.
  
  Guiducci Letizia, Burchielli Silvia, Chubuchny Vlad, Sicari Rosa, Liistro Tiziana, Corciu Anca I, Pardini Silvia, Di Cecco Pietro, Manfredi Samantha, Bucci Marco, Salvadori Piero A, Andreassi Maria Grazia, Iozzo Patricia
  
  Abstract
  
  UNLABELLED:
  Cardiovascular and metabolic vulnerability have an early developmental origin. We evaluated the potential influence of innate life factors, including the metabolism of the mother and the sex of the offspring, on cardiometabolic risk, including organ-specific insulin resistance, subclinical cardiac dysfunction, and DNA oxidative damage throughout the lifespan.
  
  METHODS:
  Two female minipigs were studied during late pregnancy, and their offspring were restudied at the ages of 1 mo (n = 11), 6 mo (n = 9), and 9 mo (n = 10, 6 offspring and 4 age-matched animals). We measured insulin-mediated glucose disposal in skeletal muscle, adipose tissue, liver, and myocardium using (18)F-FDG PET; cardiac function using 2-dimensional strain echocardiography; and DNA damage using the comet assay.
  
  RESULTS:
  Glucose metabolism showed the 2 sows to have differences similar to those in their respective 1-mo-old offspring. Over time, compared with female animals, male animals developed myocardial insulin resistance (male animals vs. female animals: 34 ± 5 vs. 58 ± 8 ?mol/min/kg at 6 mo, P = 0.03; 29 ± 8 vs. 60 ± 7 ?mol/min/kg at 9 mo, P = 0.02). Cardiac function progressively deteriorated in male animals from 1 mo (radial strain, -60% ± 7%; strain rate, -5.4 ± 0.9 s(-1)) to 6 mo (radial strain, -41% ± 5%; strain rate, -2.5 ± 0.2 s(-1), P
  CONCLUSION:
  The metabolism of minipig offspring is influenced by maternal insulin sensitivity during early life stages. Sex-related effects prevail thereafter in healthy minipigs, documenting a precocious onset of cardiometabolic vulnerability in male offspring.
  
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• [Role of pharmacologic or exercise stress echocardiography for the assessment of hemodynamics in valvular heart disease].
  G Ital Cardiol (Rome)

  2011 Oct;12(10):645-51. doi: 10.1714/945.10349.
  
  Sicari Rosa, La Falce Sabrina
  
  Abstract
  
  Stress echocardiography is emerging as an important component of stress testing in patients with valvular heart disease. Its role is not established in the routine assessment of patients, but its use is appealing for the possibility of objectively evaluating symptoms, hemodynamic changes, left ventricular function. Stress echocardiography has the advantages of being widely available, low cost and versatile for the assessment of disease severity. Nevertheless, there is a lack of convincing evidence that stress echocardiography may lead to clinical decisions and better outcomes. Therefore, large-scale prospective randomized studies focusing on patient outcomes are needed in the future.
  
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• Exercise induces rapid interstitial lung water accumulation in patients with chronic mountain sickness.
  Chest

  2012 Apr;141(4):953-958. doi: 10.1378/chest.11-0084.
  
  Pratali Lorenza, Rimoldi Stefano F, Rexhaj Emrush, Hutter Damian, Faita Francesco, Salmòn Carlos Salinas, Villena Mercedes, Sicari Rosa, Picano Eugenio, Allemann Yves, Scherrer Urs, Sartori Claudio
  
  Abstract
  
  BACKGROUND:
  Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise.
  
  METHODS:
  We assessed extravascular lung water (chest ultrasonography), pulmonary artery pressure, and left ventricular function in 15 patients with CMS and 20 control subjects at rest and during exercise at 3,600 m.
  
  RESULTS:
  Exercise at high altitude rapidly induced pulmonary interstitial fluid accumulation in all patients but one (14 of 15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in patients with CMS was accompanied by a more than two times larger increase of pulmonary artery pressure than in control subjects (P
  CONCLUSIONS:
  To our knowledge, these findings provide the first direct evidence that exercise induces rapid interstitial lung fluid accumulation and hypoxemia in patients with CMS that appear to be related to exaggerated pulmonary hypertension. We suggest that this problem contributes to exercise intolerance in patients with CMS.
  
  TRIAL REGISTRY:
  ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.
  
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• Ectopic fat storage, insulin resistance, and hypertension.
  Curr Pharm Des

  2011 ;17(28):3074-80.
  
  Sironi Anna Maria, Sicari Rosa, Folli Franco, Gastaldelli Amalia
  
  Abstract
  
  Obesity, insulin resistance, glucose intolerance/type 2 diabetes and hypertension are clustered in the metabolic syndrome representing critical risk factors for increased incidence cardio-cerebro-vascular diseases, kidney failure and cancer. Ectopic fat accumulation, i.e., accumulation in the mediastinum, liver and the abdomen, as well as generalized fat accumulation are associated with arterial hypertension, either systolic or diastolic. Several mechanisms including insulin resistance, sub-inflammatory state, increased Renin- Angiotensin-Aldosterone System (RAAS) system activity, oxidative stress, autonomic dysregulation as well as mechanical compression on the kidneys are all activated by obesity. Interestingly angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (ATII) receptor blockers, while correcting arterial hypertension, also have a positive effect on glucose metabolism and diabetes prevention, in high risk patients. The implementation of dietary, medical and surgical strategies to prevent and treat obesity, are cornerstones for the primary prevention as well as treatment of arterial hypertension.
  
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• Diagnostic and prognostic value of Doppler echocardiographic coronary flow reserve in the left anterior descending artery in hypertensive and normotensive patients [corrected].
  Heart

  2011 Nov;97(21):1758-65. doi: 10.1136/heartjnl-2011-300178.
  
  Cortigiani Lauro, Rigo Fausto, Galderisi Maurizio, Gherardi Sonia, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Vasodilator stress echocardiography allows dual imaging of regional wall motion and coronary flow reserve (CFR) on left anterior descending (LAD) artery. Hypertension may affect CFR independently of obstructive coronary artery disease (CAD) through coronary microcirculatory damage.
  
  AIMS:
  The authors sought to determine the best value of Doppler-echocardiography-derived coronary flow reserve (CFR) for detecting ?75% stenosis of the left anterior descending artery (LAD) and assessing the risk in patients with and without hypertension. Participants The study group was formed by 2089 patients (1411 hypertensive patients and 678 normotensive patients) with known or suspected coronary artery disease who underwent dipyridamole (up to 0.84 mg/kg over 6 min) stress echo with CFR assessment of LAD by Doppler and coronary angiography.
  
  RESULTS:
  Mean CFR was 2.20±0.62 in hypertensive patients and 2.36±0.70 in normotensive patients (p
  CONCLUSIONS:
  CFR on LAD provides useful information for vessel stenosis and prognostic assessment in both hypertensive and normotensive patients. However, diagnostic specificity is reduced in hypertensive.
  
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• Pericardial rather than epicardial fat is a cardiometabolic risk marker: an MRI vs echo study.
  J Am Soc Echocardiogr

  2011 Oct;24(10):1156-62. doi: 10.1016/j.echo.2011.06.013.
  
  Sicari Rosa, Sironi Anna Maria, Petz Roberta, Frassi Francesca, Chubuchny Vladislav, De Marchi Daniele, Positano Vincenzo, Lombardi Massimo, Picano Eugenio, Gastaldelli Amalia
  
  Abstract
  
  BACKGROUND:
  Several studies using echocardiography identified epicardial adipose tissue (EPI) as an important cardiometabolic risk marker. However, validation compared with magnetic resonance imaging (MRI) or computed tomography has not been performed. Moreover, pericardial adipose tissue (PERI) has recently been shown to have some correlation with cardiovascular disease risk factors. The aims of this study were to validate echocardiographic analyses compared with MRI and to evaluate which cardiac fat depot (EPI or PERI) is the most appropriate cardiovascular risk marker.
  
  METHODS:
  Forty-nine healthy subjects were studied (age range, 25-68 years; body mass index, 21-40 kg/m(2)), and PERI and EPI fat depots were measured using echocardiography and MRI. Findings were correlated with MRI visceral fat and subcutaneous fat, blood pressure, insulin sensitivity, triglycerides, cholesterol, insulin, glucose, and 10-year coronary heart disease risk.
  
  RESULTS:
  Most cardiac fat was constituted by PERI (about 77%). PERI thickness by echocardiography was well correlated with MRI area (r = 0.36, P = .009), and independently of the technique used for quantification, PERI was correlated with body mass index, waist circumference, visceral fat, subcutaneous fat, blood pressure, insulin sensitivity, triglycerides, cholesterol, glucose, and coronary heart disease risk. On the contrary, EPI thicknesses correlated only with age did not correlate significantly with MRI EPI areas, which were found to correlate with age, body mass index, subcutaneous fat, and hip and waist circumferences.
  
  CONCLUSIONS:
  Increased cardiac fat in the pericardial area is strongly associated with features of the metabolic syndrome, whereas no correlation was found with EPI, indicating that in clinical practice, PERI is a better cardiometabolic risk marker than EPI.
  
  Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.
  
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• N-terminal pro-B-type natriuretic peptide plasma levels as a potential biomarker for cardiac damage after radiotherapy in patients with left-sided breast cancer.
  Int J Radiat Oncol Biol Phys

  2012 Feb;82(2):e239-46. doi: 10.1016/j.ijrobp.2011.03.058.
  
  D'Errico Maria P, Grimaldi Luca, Petruzzelli Maria F, Gianicolo Emilio A L, Tramacere Francesco, Monetti Antonio, Placella Roberto, Pili Giorgio, Andreassi Maria Grazia, Sicari Rosa, Picano Eugenio, Portaluri Maurizio
  
  Abstract
  
  PURPOSE:
  Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B?type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer.
  
  METHODS AND MATERIALS:
  NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography.
  
  RESULTS:
  NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7?333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0?172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V(3 Gy)(%) (p = 0.001), the ratios (p = 0.01), the ratios D(15 cm)(3)/D(50%) (Gy) (p = 0.008) for the heart and correlations between plasma levels and V(2 Gy) (%) (p = 0.002), the ratios (p = 0.03), and the ratios (p = 0.05) for the ventricle.
  
  CONCLUSIONS:
  Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non?RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small percentage of organ volumes (heart or ventricle) receiving high dose levels, supporting the notion that the heart behaves as a serial organ.
  
  Copyright © 2012 Elsevier Inc. All rights reserved.
  
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• Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy.
  Pharmacogenet Genomics

  2011 Aug;21(8):469-75. doi: 10.1097/FPC.0b013e328347d2c6.
  
  Andreassi Maria Grazia, Laghi Pasini Franco, Picano Eugenio, Capecchi Pier Leopoldo, Pompella Gerarda, Foffa Ilenia, Borghini Andrea, Sicari Rosa
  
  Abstract
  
  OBJECTIVES:
  Patients with non ischemic-dilated cardiomyopathy (DCM) are characterized by an activation of the adenosinergic system and reduced coronary flow reserve (CFR) evaluated by transthoracic Doppler echocardiography during vasodilator adenosinergic stress (dipyridamole administration). The aim of this study was to assess whether genetic polymorphisms (263C>T and 1976C>T) of the A2(A) receptor gene affect CFR response in patients with DCM.
  
  METHODS:
  We enrolled a group of 80 patients with DCM (55 male; age, 62±10.3 years) and 162 healthy volunteers (55 male; age, 45.1±9.5 years). Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was determined in DCM. A2(A) receptor genotyping was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism analysis. The expression of A2(A) protein and mRNA was also assessed in healthy controls.
  
  RESULTS:
  The genotype distribution of the 263C>T (P=0.5) and 1976C>T (P=0.8) polymorphisms was not significantly different between patients and controls. Patients with 1976TT genotype had significantly lower CFR value than 1976CC patients (2.3±0.7, 2.0±0.5 and 1.9±0.4, P
  CONCLUSION:
  These data demonstrate that A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in patients with DCM, and support a direct consequences of this single nucleotide polymorphism for protein expression. Additional studies are needed to better define the functional role of this genetic variant as well as to clarify the potential clinical impact of genetics during pharmacological stress cardiac imaging.
  
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• Recommendations of the European Association of Echocardiography: how to use echo-Doppler in clinical trials: different modalities for different purposes.
  Eur J Echocardiogr

  2011 May;12(5):339-53. doi: 10.1093/ejechocard/jer051.
  
  Galderisi Maurizio, Henein Michael Y, D'hooge Jan, Sicari Rosa, Badano Luigi P, Zamorano Josè Luis, Roelandt Jos R T C,
  
  Abstract
  
  The European Association of Echocardiography (EAE) has developed the present recommendations to assist clinical researchers in the design, implementation, and conduction of echocardiographic protocols for clinical trials and to guarantee their quality. Clinical trials should be designed and conducted based on the knowledge of the pathophysiology of the clinical condition studied, the technical characteristics of the echo-Doppler modalities, and the variability of the tested parameters. These procedures are important to choose the most reliable and reproducible techniques and parameters. Quality assurance must be guaranteed by adequate training of peripheral site operators to obtain optimal echo-Doppler data and by using a core laboratory for accurate and reproducible data analysis.
  
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• Prognostic implication of stress echocardiography in 6214 hypertensive and 5328 normotensive patients.
  Eur Heart J

  2011 Jun;32(12):1509-18. doi: 10.1093/eurheartj/ehr060.
  
  Cortigiani Lauro, Bigi Riccardo, Landi Patrizia, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  Aims To compare the prognostic implication of stress echocardiography (SE) in a large cohort of hypertensive and normotensive patients with known or suspected coronary artery disease (CAD). The relative prognostic meaning of the SE result in hypertensive and normotensive patients remains to be addressed. Methods and results The study group was formed by 11 542 patients (6214 hypertensive patients; 5328 normotensive patients) who underwent exercise (n= 686), dobutamine (n= 2524), or dipyridamole (n= 8332) SE for evaluation of known (n= 4563) or suspected (n= 6979) CAD. Patients were followed up for a median of 25 months (1st quartile, 7; 3rd quartile, 57). Ischaemia on SE (new wall motion abnormality) was detected in 3209 (28%) patients. During follow-up, 1587 events (924 deaths, 663 non-fatal infarctions) occurred. Patients (n= 2764) undergoing revascularization were censored. The annual event rate was 7.0% in hypertensive and 5.7% in normotensive patients (P = 0.02) with known CAD, and 3.7% in hypertensive and 2.4% in normotensive patients (P
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• Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography.
  Eur J Echocardiogr

  2011 Mar;12(3):167-205. doi: 10.1093/ejechocard/jer021.
  
  Mor-Avi Victor, Lang Roberto M, Badano Luigi P, Belohlavek Marek, Cardim Nuno Miguel, Derumeaux Genevieve, Galderisi Maurizio, Marwick Thomas, Nagueh Sherif F, Sengupta Partho P, Sicari Rosa, Smiseth Otto A, Smulevitz Beverly, Takeuchi Masaaki, Thomas James D, Vannan Mani, Voigt Jens-Uwe, Zamorano Jose Luis
  
  Abstract
  
  Echocardiographic imaging is ideally suited for the evaluation of cardiac mechanics because of its intrinsically dynamic nature. Because for decades, echocardiography has been the only imaging modality that allows dynamic imaging of the heart, it is only natural that new, increasingly automated techniques for sophisticated analysis of cardiac mechanics have been driven by researchers and manufacturers of ultrasound imaging equipment. Several such techniques have emerged over the past decades to address the issue of reader's experience and inter-measurement variability in interpretation. Some were widely embraced by echocardiographers around the world and became part of the clinical routine, whereas others remained limited to research and exploration of new clinical applications. Two such techniques have dominated the research arena of echocardiography: (1) Doppler-based tissue velocity measurements, frequently referred to as tissue Doppler or myocardial Doppler, and (2) speckle tracking on the basis of displacement measurements. Both types of measurements lend themselves to the derivation of multiple parameters of myocardial function. The goal of this document is to focus on the currently available techniques that allow quantitative assessment of myocardial function via image-based analysis of local myocardial dynamics, including Doppler tissue imaging and speckle-tracking echocardiography, as well as integrated back- scatter analysis. This document describes the current and potential clinical applications of these techniques and their strengths and weaknesses, briefly surveys a selection of the relevant published literature while highlighting normal and abnormal findings in the context of different cardiovascular pathologies, and summarizes the unresolved issues, future research priorities, and recommended indications for clinical use.
  
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• Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography.
  J Am Soc Echocardiogr

  2011 Mar;24(3):277-313. doi: 10.1016/j.echo.2011.01.015.
  
  Mor-Avi Victor, Lang Roberto M, Badano Luigi P, Belohlavek Marek, Cardim Nuno Miguel, Derumeaux Geneviève, Galderisi Maurizio, Marwick Thomas, Nagueh Sherif F, Sengupta Partho P, Sicari Rosa, Smiseth Otto A, Smulevitz Beverly, Takeuchi Masaaki, Thomas James D, Vannan Mani, Voigt Jens-Uwe, Zamorano José Luis
  
  Abstract
  
  Echocardiographic imaging is ideally suited for the evaluation of cardiac mechanics because of its intrinsically dynamic nature. Because for decades, echocardiography has been the only imaging modality that allows dynamic imaging of the heart, it is only natural that new, increasingly automated techniques for sophisticated analysis of cardiac mechanics have been driven by researchers and manufacturers of ultrasound imaging equipment.Several such technique shave emerged over the past decades to address the issue of reader's experience and inter measurement variability in interpretation.Some were widely embraced by echocardiographers around the world and became part of the clinical routine,whereas others remained limited to research and exploration of new clinical applications.Two such techniques have dominated the research arena of echocardiography: (1) Doppler based tissue velocity measurements,frequently referred to as tissue Doppler or myocardial Doppler, and (2) speckle tracking on the basis of displacement measurements.Both types of measurements lend themselves to the derivation of multiple parameters of myocardial function. The goal of this document is to focus on the currently available techniques that allow quantitative assessment of myocardial function via image-based analysis of local myocardial dynamics, including Doppler tissue imaging and speckle-tracking echocardiography, as well as integrated backscatter analysis. This document describes the current and potential clinical applications of these techniques and their strengths and weaknesses,briefly surveys a selection of the relevant published literature while highlighting normal and abnormal findings in the context of different cardiovascular pathologies, and summarizes the unresolved issues, future research priorities, and recommended indications for clinical use.
  
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• The use of pocket-size imaging devices: a position statement of the European Association of Echocardiography.
  Eur J Echocardiogr

  2011 Feb;12(2):85-7. doi: 10.1093/ejechocard/jeq184.
  
  Sicari Rosa, Galderisi Maurizio, Voigt Jens-Uwe, Habib Gilbert, Zamorano Jose L, Lancellotti Patrizio, Badano Luigi P
  
  Abstract
  
  Pocket-size imaging devices are a completely new type of echo machines which have recently reached the market. They are very cheap, smartphone-size hand-held echo machines with limited technical capabilities. The aim of this European Association of Echocardiography (EAE) position paper is to provide recommendations on the use of pocket-size imaging devices in the clinical arena by profiling the educational needs of potential users other than cardiologists experts in echo. EAE recommendations about pocket-size imaging devices can be summarized in: (1) pocket-size imaging devices do not provide a complete diagnostic echocardiographic examination. The range of indications for their use is therefore limited. (2) Imaging assessment with pocket-size imaging devices should be reported as part of the physical examination of the patient. Image data should be stored according to the applicable national rules for technical examinations. (3) With the exception of cardiologists who are certified for transthoracic echocardiography according to national legislation, specific training and certification is recommended for all users. The certification should be limited to the clinical questions that can potentially be answered by pocket-size devices. (4) The patient has to be informed that an examination with the current generation of pocket-size imaging devices does not replace a complete echocardiogram.
  
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• Prognostic value of left and right coronary flow reserve assessment in nonischemic dilated cardiomyopathy by transthoracic Doppler echocardiography.
  J Card Fail

  2011 Jan;17(1):39-46. doi: 10.1016/j.cardfail.2010.08.003.
  
  Rigo Fausto, Ciampi Quirino, Ossena Giovanni, Grolla Elisabetta, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can be reduced in nonischemic dilated cardiomyopathy (DCM). The aim of this study was to assess the prognostic value of CFR in LAD and in the posterior descending artery (PD) in DCM patients.
  
  METHODS:
  Seventy-two DCM patients (44 men, mean age 64 ± 13 years) underwent dipyridamole (0.84 mg/kg in 6 minutes) stress echo. CFR was defined as the ratio between maximal vasodilation and rest peak diastolic flow velocity in LAD and PD.
  
  RESULTS:
  CFR was abnormal in LAD in 42 out of 72 patients and in PD in 31 out of 55. All patients completed the clinical follow-up, and 56 patients completed the echocardiographic follow-up. During median follow-up of 42 months, 33 events (7 deaths, 26 major cardiac events) occurred. Event rate was markedly higher for patients with reduced CFR compared with DCM patients with normal CRF in LAD (0 vs 19 events; P
  CONCLUSIONS:
  In DCM patients, impairment of CFR in LAD and PD is related to a worse outcome; CFR impairment is more relevant when it occurs in LAD. PD evaluation may be redundant and time-consuming, because the additive value is small and the feasibility suboptimal.
  
  Copyright © 2011 Elsevier Inc. All rights reserved.
  
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• [Common pathogenetic features between calcific aortic stenosis and atherosclerosis: role of receptor for advanced glycation end-products].
  Recenti Prog Med

  2010 Oct;101(10):413-7.
  
  Corciu Anca Irina, Del Turco Serena, Sicari Rosa, Basta Giuseppina
  
  Abstract
  
  Clinical and experimental studies identified several similarities between calcific aortic stenosis and atherosclerosis, suggesting the involvement of similar pathogenic pathways in both conditions.There are several molecules involved in regulating the development, progression and calcification of the valve sclerosis and in growth and complications of atherosclerotic plaque. Among these molecules, the receptor of advanced glycation end-products, a multi-ligand receptor involved in the pathogenesis of several degenerative, inflammatory and immune diseases, could have an important regulatory role in both diseases and therefore worthy of study as a potential target therapeutic for both conditions.
  
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• Comparison of prognostic value of echographic [corrected] risk score with the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry in Acute Coronary Events (GRACE) risk scores in acute coronary syndrome.
  Am J Cardiol

  2010 Dec;106(12):1709-16. doi: 10.1016/j.amjcard.2010.08.024.
  
  Bedetti Gigliola, Gargani Luna, Sicari Rosa, Gianfaldoni Maria Luisa, Molinaro Sabrina, Picano Eugenio
  
  Abstract
  
  Risk stratification in patients with acute coronary syndromes (ACS) is achieved today by clinical models, "blind" to the prognostic support of imaging methods. To assess the value of simple at rest cardiac chest sonography in predicting the intra- and extrahospital risk of death or myocardial infarction, we enrolled 470 consecutive in-patients (312 men, age 71 ± 12 years) who had been admitted for ACS. On admission, all had received a clinical score using the Global Registry in Acute Coronary Events and Thrombolysis in Myocardial Infarction systems and, within 1 to 12 hours, a comprehensive cardiac-chest ultrasound scan. Each of the 16 echocardiographic parameters evaluating left and right, systolic and diastolic, ventricular function and structure, was scored from 0 (normal) to 3 (severely abnormal). The median follow-up was 5 months (interquartile range 1 to 10). Patients with hard events (n = 102) could be separated from patients without events (n = 368) using the Global Registry in Acute Coronary Events score, Thrombolysis in Myocardial Infarction score, and several echocardiographic parameters. On multivariate Cox analysis, ejection fraction (hazard ratio 1.45, 95% confidence interval 1.02 to 2.08, p = 0.040), tricuspid annular plane systolic excursion (hazard ratio 1.66, 95% confidence interval 1.13 to 2.45, p = 0.010) and ultrasound lung comets (hazard ratio 1.69, 95% confidence interval 1.25 to 2.27, p = 0.001) were independent predictors of cardiac events. The 3-variable echocardiographic score (from 0, normal to 9, severe abnormalities in ejection fraction, ultrasound lung comets, and tricuspid annular plane systolic excursion) effectively stratified patients and added value (hazard ratio 2.52, 95% confidence interval 1.89 to 3.37, p
  Copyright © 2010 Elsevier Inc. All rights reserved.
  
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• Prognostic effect of coronary flow reserve in women versus men with chest pain syndrome and normal dipyridamole stress echocardiography.
  Am J Cardiol

  2010 Dec;106(12):1703-8. doi: 10.1016/j.amjcard.2010.08.011.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  The aim of this study was to investigate the prognostic effect of coronary flow reserve (CFR) on left anterior descending artery (LAD) in women and men with chest pain of unknown origin and normal stress echocardiogram. The study population consisted of 1,660 patients (906 women, 754 men) with chest pain syndrome, no wall motion abnormality on echocardiogram at rest, and dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiogram negative for wall motion criteria. All had undergone stress echocardiography with combined evaluation of CFR on LAD by Doppler. A CFR value ?2.0 was considered abnormal. Median duration of follow-up was 19 months (interquartile range 10 to 34). Abnormal CFR was assessed in 171 women (19%) and 147 men (19%, p = 0.80). During follow-up, 80 events (20 deaths, 13 ST-elevation myocardial infarctions, and 47 non-ST-elevation myocardial infarctions) occurred. In addition, 128 patients underwent revascularization and were censored. CFR ?2.0 on LAD was independently associated with prognosis in women (hazard ratio [HR] 16.48, 95% confidence interval [CI] 7.17 to 37.85, p 2.0 were, respectively, 27% and 2% in women (p
  Copyright © 2010 Elsevier Inc. All rights reserved.
  
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• Clinical and prognostic role of pressure-volume relationship in the identification of responders to cardiac resynchronization therapy.
  Am Heart J

  2010 Nov;160(5):906-14. doi: 10.1016/j.ahj.2010.07.019.
  
  Ciampi Quirino, Pratali Lorenza, Citro Rodolfo, Villari Bruno, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  The identification of responders remains challenging in cardiac resynchronization therapy (CRT). Pressure-volume relationship (PVR) is a method to evaluate left ventricular myocardial contractility during stress. The aim of the study was to assess the role of PVR to identify responders to CRT.
  
  METHODS:
  Seventy-two patients (57% with ischemic etiology) referred to CRT: ejection fraction ? 35%, New York Heart Association ? III and QRS duration ? 120 milliseconds, underwent dobutamine stress echocardiography (up to 40 ?g/kg per minute). PVR was defined as systolic cuff pressure/end-systolic volume index difference between rest-peak dobutamine stress echocardiography. Responders were identified by clinical and/or echocardiographic (end-systolic volume decrease ? 15%) follow-up criteria. We divided retrospectively the patient population into 2 groups, accordingly to the presence of myocardial contractile reserve that was set at the value of PVR (0.72 mm Hg/mL per square meter) obtained by a receiver operating characteristic analysis.
  
  RESULTS:
  During a median follow-up of 12 months, 8 patients (11%) died. Patients with lower PVR, showed higher brain natriuretic peptide levels (853 ± 1211 vs 342 ± 239, P = .044) larger left ventricular end-diastolic (196 ± 82 mL vs 152 ± 39 mL, P = .005) and end-systolic (147 ± 66 vs 112 ± 30 mL, P = .006) volumes. Intraventricular dyssynchrony was similar in the 2 groups (88 ± 45 vs 70 ± 32 milliseconds, P = .175). Patients with higher PVR presented a larger incidence of clinical (86% vs 46% P
  CONCLUSION:
  Patients with preserved contractility, assessed by PVR during stress echocardiography show a favor clinical outcome and left ventricular reverse remodeling after CRT. In particular, PVR may have a significant clinical role in patients undergoing CRT, providing critical information for risk stratification.
  
  Copyright © 2010 Mosby, Inc. All rights reserved.
  
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• Innate inflammation in myocardial perfusion and its implication for heart failure.
  Ann N Y Acad Sci

  2010 Oct;1207():107-15. doi: 10.1111/j.1749-6632.2010.05724.x.
  
  Picano Eugenio, Morales Maria Aurora, del Ry Silvia, Sicari Rosa
  
  Abstract
  
  Heart failure is characterized by a chronic inflammatory status, with high circulating levels of inflammatory cytokines significantly correlated with deterioration of functional capacity, cardiac performance, and coronary flow reserve--the latter occurring even with normal systemic endothelial function. Impaired coronary flow reserve in heart failure is poorly related to systemic inflammation levels and somewhat matched by a reduction in myocardial contractile reserve. Both coronary flow and myocardial functional reserve can be imaged noninvasively and can be useful clinically for disease severity titration, diagnostic anticipation, and prognostic stratification. Coronary microcirculatory dysfunction can be a trigger of disease and a potential target for therapeutic intervention in heart failure patients. Clinical observational studies showed a striking beneficial effect of endogenous adenosine accumulation on symptoms, exercise capacity, and left ventricular function in chronic heart failure, but this needs to be confirmed in prospective randomized large-scale trials.
  
  © 2010 New York Academy of Sciences.
  
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• Echocardiography in aortic diseases: EAE recommendations for clinical practice.
  Eur J Echocardiogr

  2010 Sep;11(8):645-58. doi: 10.1093/ejechocard/jeq056.
  
  Evangelista Arturo, Flachskampf Frank A, Erbel Raimund, Antonini-Canterin Francesco, Vlachopoulos Charalambos, Rocchi Guido, Sicari Rosa, Nihoyannopoulos Petros, Zamorano Jose, , , Pepi Mauro, Breithardt Ole-A, Plonska-Gosciniak Edyta
  
  Abstract
  
  Echocardiography plays an important role in the diagnosis and follow-up of aortic diseases. Evaluation of the aorta is a routine part of the standard echocardiographic examination. Transthoracic echocardiography (TTE) permits adequate assessment of several aortic segments, particularly the aortic root and proximal ascending aorta. Transoesophageal echocardiography (TOE) overcomes the limitations of TTE in thoracic aorta assessment. TTE and TOE should be used in a complementary manner. Echocardiography is useful for assessing aortic size, biophysical properties, and atherosclerotic involvement of the thoracic aorta. Although TOE is the technique of choice in the diagnosis of aortic dissection, TTE may be used as the initial modality in the emergency setting. Intimal flap in proximal ascending aorta, pericardial effusion/tamponade, and left ventricular function can be easily visualized by TTE. However, a negative TTE does not rule out aortic dissection and other imaging techniques must be considered. TOE should define entry tear location, mechanisms and severity of aortic regurgitation, and true lumen compression. In addition, echocardiography is essential in selecting and monitoring surgical and endovascular treatment and in detecting possible complications. Although other imaging techniques such as computed tomography and magnetic resonance have a greater field of view and may yield complementary information, echocardiography is portable, rapid, accurate, and cost-effective in the diagnosis and follow-up of most aortic diseases.
  
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• Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism: European Association of Echocardiography (EAE) (a registered branch of the ESC).
  Eur J Echocardiogr

  2010 Jul;11(6):461-76. doi: 10.1093/ejechocard/jeq045.
  
  Pepi Mauro, Evangelista Arturo, Nihoyannopoulos Petros, Flachskampf Frank A, Athanassopoulos George, Colonna Paolo, Habib Gilbert, Ringelstein E Bernd, Sicari Rosa, Zamorano Jose Luis, Sitges Marta, Caso Pio,
  
  Abstract
  
  Embolism of cardiac origin accounts for around 15-30% of ischaemic strokes. Strokes due to cardioembolism are generally severe and early and long-term recurrence and mortality are high. The diagnosis of a cardioembolic source of stroke is frequently uncertain and relies on the identification of a potential cardiac source of embolism in the absence of significant autochthone cerebrovascular occlusive disease. In this respect, echocardiography (both transthoracic and/or transoesophageal) serves as a cornerstone in the evaluation, diagnosis, and management of these patients. A clear understanding of the various types of cardiac conditions associated with cardioembolic stroke and their intrinsic risk is therefore very important. This article reviews potential cardiac sources of embolism and discusses the role of echocardiography in clinical practice. Recommendations for the use of echocardiography in the diagnosis of cardiac sources of embolism are given including major and minor conditions associated with the risk of embolism.
  
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• Frequent subclinical high-altitude pulmonary edema detected by chest sonography as ultrasound lung comets in recreational climbers.
  Crit Care Med

  2010 Sep;38(9):1818-23. doi: 10.1097/CCM.0b013e3181e8ae0e.
  
  Pratali Lorenza, Cavana Marco, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  OBJECTIVE:
  The ultrasound lung comets detected by chest sonography are a simple, noninvasive, semiquantitative sign of increased extravascular lung water. The aim of this study was to evaluate, by chest sonography, the incidence of interstitial pulmonary edema in recreational high-altitude climbers.
  
  DESIGN:
  Observational study.
  
  SUBJECTS:
  Eighteen healthy subjects (mean age 45 +/- 10 yrs, ten males) participating in a high-altitude trek in Nepal.
  
  INTERVENTIONS:
  Chest and cardiac sonography at sea level and at different altitudes during ascent. Ultrasound lung comets were evaluated on anterior chest at 28 predefined scanning sites.
  
  MEASUREMENTS AND MAIN RESULTS:
  At individual patient analysis, ultrasound lung comets during ascent appeared in 15 of 18 subjects (83%) at 3440 m above sea level and in 18 of 18 subjects (100%) at 4790 m above sea level in the presence of normal left and right ventricular function and pulmonary artery systolic pressure rise (sea level = 24 +/- 5 mm Hg vs. peak ascent = 42 +/- 11 mm Hg, p
  CONCLUSIONS:
  In recreational climbers, chest sonography revealed a high prevalence of clinically silent interstitial pulmonary edema mirrored by decreased O(2) saturation, whereas no statistically significant relationship with pulmonary artery systolic pressure was observed during ascent.
  
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• [A novel lamin A/C mutation in a family with dilated cardiomyopathy and a strong history of sudden cardiac death].
  Recenti Prog Med

  2010 Mar;101(3):127-30.
  
  Andreassi Maria Grazia, Botto Nicoletta, Vittorini Simona, Pulignani Silvia, Aquaro Giovanni, Sicari Rosa
  
  Abstract
  
  Diseases related to lamin A/C mutations (laminopathies) are extremely heterogeneous. The common cardiac phenotype is idiopathic dilated cardiomyopathy with atrioventricular block and/or arrhythmias. Moreover, patients with lamin A/C gene mutations are at increased risk for sudden cardiac death. Here we present a family with a strong positive history of sudden cardiac death in presence of idiopathic dilated cardiomyopathy and cardiac conduction abnormalities, related to a novel lamin A/C mutation in exon 3.
  
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• [Differential diagnosis of dyspnea: the incremental value of lung ultrasound].
  Recenti Prog Med

  2010 Feb;101(2):78-82.
  
  Gargani Luna, Fontana Marianna, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  Acute dyspnea as a presenting symptom is a frequent challenge for physicians. Difficulties in establishing a correct diagnosis may lead to late institution of appropriate medical therapy.The authors describe the case of a 77 year-old man with both chronic obstructive pulmonary disease and cardiac insufficiency, presenting with episodes of acute dyspnea, whose ethiology has been revealed by lung ultrasound.
  
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• Feasibility of real-time three-dimensional stress echocardiography: pharmacological and semi-supine exercise.
  Cardiovasc Ultrasound

  2010 Mar;8():10. doi: 10.1186/1476-7120-8-10.
  
  Pratali Lorenza, Molinaro Sabrina, Corciu Anca I, Pasanisi Emilio M, Scalese Marco, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  Real time three dimensional (RT3D) echocardiography is an accurate and reproducible method for assessing left ventricular shape and function.
  
  AIM:
  assess the feasibility and reproducibility of RT3D stress echocardiography (SE) (exercise and pharmacological) in the evaluation of left ventricular function compared to 2D.
  
  METHODS AND RESULTS:
  One hundred eleven patients with known or suspected coronary artery disease underwent 2D and RT3DSE. The agreement in WMSI, EDV, ESV measurements was made off-line.The feasibility of RT-3DSE was 67%. The inter-observer variability for WMSI by RT3D echo was higher during exercise and with suboptimal quality images (good: k = 0.88; bad: k = 0.69); and with high heart rate both for pharmacological (HR or = 100 bpm, k = 0.49) and exercise SE (HR or = 120 bpm, k = 0.78). The RT3D reproducibility was high for ESV volumes (0.3 +/- 14 ml; CI 95%: -27 to 27 ml; p = n.s.).
  
  CONCLUSIONS:
  RT3DSE is more vulnerable than 2D due to tachycardia, signal quality, patient decubitus and suboptimal resting image quality, making exercise RT3DSE less attractive than pharmacological stress.
  
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• Recommendations for the practice of echocardiography in infective endocarditis.
  Eur J Echocardiogr

  2010 Mar;11(2):202-19. doi: 10.1093/ejechocard/jeq004.
  
  Habib Gilbert, Badano Luigi, Tribouilloy Christophe, Vilacosta Isidre, Zamorano Jose Luis, Galderisi Maurizio, Voigt Jens-Uwe, Sicari Rosa, Cosyns Bernard, Fox Kevin, Aakhus Svend,
  
  Abstract
  
  Echocardiography plays a key role in the assessment of infective endocarditis (IE). It is useful for the diagnosis of endocarditis, the assessment of the severity of the disease, the prediction of short- and long-term prognosis, the prediction of embolic events, and the follow-up of patients under specific antibiotic therapy. Echocardiography is also useful for the diagnosis and management of the complications of IE, helping the physician in decision-making, particularly when a surgical therapy is considered. Finally, intraoperative echocardiography must be performed in IE to help the surgeon in the assessment and management of patients with IE during surgery. The current 'recommendations for the practice of echocardiography in infective endocarditis' aims to provide both an updated summary concerning the value and limitations of echocardiography in IE, and clear and simple recommendations for the optimal use of both transthoracic and transoesophageal echocardiography in IE.
  
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• Implication of the continuous prognostic spectrum of Doppler echocardiographic derived coronary flow reserve on left anterior descending artery.
  Am J Cardiol

  2010 Jan;105(2):158-62. doi: 10.1016/j.amjcard.2009.08.669.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Bovenzi Francesco, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal-abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 +/- 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 +/- 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>or=70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non-ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (
  Copyright 2010 Elsevier Inc. All rights reserved.
  
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• Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery: the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA).
  Eur J Anaesthesiol

  2010 Feb;27(2):92-137. doi: 10.1097/EJA.0b013e328334c017.
  
  Poldermans Don, Bax Jeroen J, Boersma Eric, De Hert Stefan, Eeckhout Erik, Fowkes Gerry, Gorenek Bulent, Hennerici Michael G, Iung Bernard, Kelm Malte, Kjeldsen Keld Per, Kristensen Steen Dalby, Lopez-Sendon Jose, Pelosi Paolo, Philippe François, Pierard Luc, Ponikowski Piotr, Schmid Jean-Paul, Sellevold Olav Fm, Sicari Rosa, Van den Berghe Greet, Vermassen Frank, Hoeks Sanne E, Vanhorebeek Ilse, Vahanian Alec, Auricchio Angelo, Bax Jeroen J, Ceconi Claudio, Dean Veronica, Filippatos Gerasimos, Funck-Brentano Christian, Hobbs Richard, Kearn Peter, McDonag Theresa, McGregor Keith, Popescu Bogdan A, Reiner Zeljko, Sechtem Udo, Sirnes Per Anton, Tendera Michal, Vardas Panos, Widimsky Petr, De Caterina Raffaele, Agewall Stefan, Al Attar Nawwar, Andreotti Felicita, Anker Stefan D, Baron-Esquivias Gonzalo, Berkenboom Guy, Chapoutot Laurent, Cifkova Renata, Faggiano Pompilio, Gibbs Simon, Hansen Henrik Steen, Iserin Laurence, Israel Carsten W, Kornowski Ran, Eizagaechevarria Nekane Murga, Pepi Mauro, Piepoli Massimo, Priebe Hans Joachim, Scherer Martin, Stepinska Janina, Taggart David, Tubaro Marco, ,
  
  
  
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• Pressure-volume relationship during dobutamine stress echocardiography predicts exercise tolerance in patients with congestive heart failure.
  J Am Soc Echocardiogr

  2010 Jan;23(1):71-8. doi: 10.1016/j.echo.2009.11.001.
  
  Ciampi Quirino, Pratali Lorenza, Bombardini Tonino, Della Porta Michele, Petruzziello Bruno, Villari Bruno, Picano Eugenio, Sicari Rosa
  
  Abstract
  
  BACKGROUND:
  The pressure-volume relationship (PVR) is a useful method for evaluating left ventricular (LV) myocardial contractility during dobutamine stress echocardiography (DSE). The investigators assessed PVRs, systolic and diastolic function, B-type natriuretic peptide (BNP) levels, and aerobic exercise capacity in patients with congestive heart failure (CHF).
  
  METHODS:
  A total of 84 patients with CHF (mean age, 68 +/- 9 years) underwent high-dose DSE. PVR was defined as the systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. Of these, 67 patients also underwent cardiopulmonary exercise testing. The patients were divided into 3 equal groups on the basis of PVR: lower, intermediate, and higher.
  
  RESULTS:
  PVRs were significantly lower in more symptomatic patients (New York Heart Association class II vs III) (2.17 +/- 1.99 vs 0.91 +/- 0.72 mm Hg/mL/m(2), P or= 14) showed significantly lower PVRs compared with patients with normal or slightly abnormal LV filling pressures (1.1 +/- 1.1 vs 2.96 +/- 3.11 mm Hg/mL/m(2), P = .006). Patients with higher PVRs showed lower logarithmically transformed BNP levels (2.0 +/- 0.5, 2.5 +/- 0.3, and 2.6 +/- 0.5 pg/mL; P
  CONCLUSIONS:
  In patients with CHF, impaired noninvasively assessed myocardial contractility is related to impaired systolic and diastolic function, higher BNP levels, and poorer exercise tolerance.
  
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• European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography.
  Eur J Echocardiogr

  2009 Dec;10(8):893-905. doi: 10.1093/ejechocard/jep151.
  
  Popescu Bogdan A, Andrade Maria J, Badano Luigi P, Fox Kevin F, Flachskampf Frank A, Lancellotti Patrizio, Varga Albert, Sicari Rosa, Evangelista Arturo, Nihoyannopoulos Petros, Zamorano Jose L, , Derumeaux Genevieve, Kasprzak Jaroslaw D, Roelandt Jos R T C
  
  Abstract
  
  The main mission statement of the European Association of Echocardiography (EAE) is 'to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe'. As competence and quality control issues are increasingly recognized by patients, physicians, and payers, the EAE has established recommendations for training, competence, and quality improvement in echocardiography. The purpose of this document is to provide the requirements for training and competence in echocardiography, to outline the principles of quality measurement, and to recommend a set of measures for improvement, with the ultimate goal of raising the standards of echocardiographic practice in Europe.
  
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• [Patent foramen ovale: "les liaisons dangereuses" between anatomy and genetics].
  Recenti Prog Med

  2009 ;100(7-8):356-60.
  
  Botto Nicoletta, Ait-Ali Lamia, Sicari Rosa, Spadoni Isabella, Andreassi Maria Grazia
  
  Abstract
  
  We reported a case of two 24-year-old and 17-year-old male patients with episode of transient ischemic attacks and diagnosed as having patent foramen ovale (PFO). One patient had heterozygosity for the factor V Leiden mutation, and one other had heterozygosity for prothrombin G20210A mutation. Both of them were also carriers for MTHFR 677T genotype with elevated plasma levels of homocysteine (22.3 +/- 3.9 micromol/L). These findings strongly confirm and emphasize the importance of the genetic screening for thrombotic mutations in young patients with PFO-related ischemic events in order to improve secondary prevention strategies.
  
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• Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery.
  Eur Heart J

  2009 Nov;30(22):2769-812. doi: 10.1093/eurheartj/ehp337.
  
  , , Poldermans Don, Bax Jeroen J, Boersma Eric, De Hert Stefan, Eeckhout Erik, Fowkes Gerry, Gorenek Bulent, Hennerici Michael G, Iung Bernard, Kelm Malte, Kjeldsen Keld Per, Kristensen Steen Dalby, Lopez-Sendon Jose, Pelosi Paolo, Philippe François, Pierard Luc, Ponikowski Piotr, Schmid Jean-Paul, Sellevold Olav F M, Sicari Rosa, Van den Berghe Greet, Vermassen Frank
  
  
  
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• Ozone and cardiovascular injury.
  Cardiovasc Ultrasound

  2009 Jun;7():30. doi: 10.1186/1476-7120-7-30.
  
  Srebot Vera, Gianicolo Emilio A L, Rainaldi Giuseppe, Trivella Maria Giovanna, Sicari Rosa
  
  Abstract
  
  Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases. The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans 1. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke 2) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality 3. Most of the evidence comes from studies of ambient particles concentrations. However, in Europe and elsewhere, the air pollution profile has gradually changed toward a more pronounced photochemical component. Ozone is one of the most toxic components of the photochemical air pollution mixture. Indeed, the biological basis for these observations has not been elucidated. In the present review, the role of ozone as chemical molecule will be firstly considered. Secondly, pathogenetic mechanisms connecting the atmospheric ozone level and cardiovascular pathology will be examined. Thirdly, the literature relating hospitalization frequency, morbidity and mortality due to cardiovascular causes and ozone concentration will be studied. The correlation between ozone level and occurrence of acute myocardial infarction will be eventually discussed.
  
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• Diffuse, marked, reversible impairment in coronary microcirculation in stress cardiomyopathy: a Doppler transthoracic echo study.
  Ann Med

  2009 ;41(6):462-70. doi: 10.1080/07853890903022793.
  
  Rigo Fausto, Sicari Rosa, Citro Rodolfo, Ossena Giovanni, Buja Paolo, Picano Eugenio
  
  Abstract
  
  UNLABELLED:
  The aim of the study was to assess coronary flow reserve (CFR) in tako-tsubo cardiomyopathy (TC).
  
  METHODS AND RESULTS:
  Thirty consecutive patients (5 males; age 68+/-12 years) meeting diagnostic criteria for TC were evaluated with transthoracic dipyridamole (0.84 mg/kg over 6 min) stress echo and pulsed Doppler CFR assessment on mid-distal left anterior descending (LAD) and posterior descending of right coronary artery (PD). Wall motion score index (WMSI) was evaluated at base-line and during stress. All patients were followed up clinically and-on day 1, day 7 (+/-2 days), and at 6 months-by repeat stress echo. Thirty gender- matched controls were also studied. CFR was obtained in all patients on LAD and in 25 on PD. All showed a transient apical ballooning in the acute phase (day 1 of admission), with progressive recovery of function at follow-up (WMSI, day 1 = 1.7+/-0.2; day 7 = 1.4+/-0.14; 6 months = 1.0+/-0.1; P
  CONCLUSION:
  TC is characterized by a profound, diffuse coronary microcirculatory disturbance in the acute phase, with early reversal to near-normal values within a few days, paralleling the functional recovery in regional wall motion.
  
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• Post-exercise contractility, diastolic function, and pressure: operator-independent sensor-based intelligent monitoring for heart failure telemedicine.
  Cardiovasc Ultrasound

  2009 May;7():21. doi: 10.1186/1476-7120-7-21.
  
  Bombardini Tonino, Gemignani Vincenzo, Bianchini Elisabetta, Pasanisi Emilio, Pratali Lorenza, Pianelli Mascia, Faita Francesco, Giannoni Massimo, Arpesella Giorgio, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates.
  
  AIM:
  To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system.
  
  METHODS:
  We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 +/- 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording.
  
  RESULTS:
  Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p 1 in 20 patients and in none of the controls (p 1 in only 3 patients (p
  CONCLUSION:
  Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes--in our study, all of these were monitored by a non-invasive wearable sensor.
  
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• Risk stratification by stress echocardiography beyond wall motion analysis.
  JACC Cardiovasc Imaging

  2009 Mar;2(3):260-2. doi: 10.1016/j.jcmg.2008.12.007.
  
  Sicari Rosa
  
  
  
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• Imaging and laboratory biomarkers in cardiovascular disease.
  Curr Pharm Des

  2009 ;15(10):1131-41.
  
  Andreassi Maria Grazia, Gastaldelli Amalia, Clerico Aldo, Salvadori Piero A, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  Imaging and laboratory biomarkers are an essential support to modern practice of medicine, allowing a better identification, severity titration, staging and follow-up of atherosclerosis and heart failure disease. This review provides an overview of imaging, biochemical and genetic biomarkers used in clinical practice and for research purposes in order to evaluate the 4 different aspect of patient vulnerability to cardiovascular disease: arterial; blood; myocardial; metabolic vulnerability. Yet, no single perfect biomarker exists and there is wide room for optimization and integration between clinical evaluation and biomarker evaluation. In general, a targeted approach tailored on the individual patient should be preferred to a carpet diagnostic bombing, which will lead to an exorbitant multiplier of costs, risks and inappropriate testing.
  
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• [Papillary thyroid carcinoma of an interventional cardiologist. A case report].
  Recenti Prog Med

  2009 Feb;100(2):80-3.
  
  Venneri Lucia, Foffa Ilenia, Sicari Rosa
  
  Abstract
  
  A 52-year old female cardiologist with 16 year radiation exposure in Cath Lab as an interventional cardiologist developed a multifocal papillary thyroid carcinoma. Dosimetric (below apron) cumulative exposure totalled 56 mSv, corresponding to 2,800 chest radiographs. The patient also carried genetic polymorphisms of genes (XRCC1 and XRCC3) involved in DNA repair, increasing the cancer risk after ionizing radiation exposure. Dose optimization and diligent radioprotection are essential to minimize cancer risk in professionally exposed cardiologist. Good dosimetric practice is essential to establish a legally plausible cause-effect relationship between exposure and damage.
  
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• Stress echocardiography for the risk stratification of patients following coronary bypass surgery.
  Int J Cardiol

  2010 Sep;143(3):337-42. doi: 10.1016/j.ijcard.2009.03.063.
  
  Cortigiani Lauro, Bigi Riccardo, Sicari Rosa, Landi Patrizia, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  OBJECTIVES:
  The aim of the study was to assess the prognostic value of stress echocardiography after surgical revascularization.
  
  METHODS:
  We evaluated 500 (100 women) patients who had undergone exercise or pharmacological SE after a median of 69 months after coronary artery by-pass grafting (CABG). Of these, 351 (70%) complained of symptoms suggestive of ischemic origin while 149 (30%) were tested for asymptomatic progression of the disease.
  
  RESULTS:
  SE was positive for ischemia in 196 (39%) patients. During a median follow-up of 25 months, 61 patients died, 33 had a nonfatal myocardial infarction, and 112 underwent late (>3 months) revascularization. Multivariable Cox' regression analysis indicated age (HR=1.04; 95% CI 1.01-1.06; p
  DISCUSSION:
  SE represents an effective tool for the risk stratification of patients with previous CABG independently of the presence of symptoms suggestive of ischemic origin.
  
  Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
  
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• Impact of gender on risk stratification by stress echocardiography.
  Am J Med

  2009 Mar;122(3):301-9. doi: 10.1016/j.amjmed.2008.11.003.
  
  Cortigiani Lauro, Sicari Rosa, Bigi Riccardo, Landi Patrizia, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  OBJECTIVE:
  To compare the prognostic value of stress echocardiography results in men and women with known and suspected coronary artery disease.
  
  METHODS:
  We analyzed the data of 8737 patients (5529 men and 3208 women) who underwent stress echocardiography (exercise in 523 patients, dipyridamole in 6227 patients, dobutamine in 1987) for evaluating known (n=3857) or suspected (n=4880) coronary artery disease. Patients were followed up for the occurrence of overall mortality or nonfatal myocardial infarction.
  
  RESULTS:
  During a median follow-up of 25 months, 1218 cardiac events (693 deaths and 525 infarctions) occurred. Moreover, 2263 patients (1731 men [31%] and 532 women [17%]; P<.0001 underwent coronary revascularization and were censored. stress echocardiography results added prognostic information to that of clinical findings resting wall motion score index in men women with both known suspected artery disease. patients disease had a higher event rate than the presence ischemia. annual was worse for nondiabetic but not diabetic age neutral effect sexes. without ischemia women. aged less years or more those diabetes.>
  CONCLUSION:
  Prognosis is at least comparable in men and women with ischemia and in those with coronary artery disease and no ischemia at stress echocardiography. In these clinical settings, availability for major procedures should be similar for both genders.
  
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• Additive prognostic value of coronary flow reserve in patients with chest pain syndrome and normal or near-normal coronary arteries.
  Am J Cardiol

  2009 Mar;103(5):626-31. doi: 10.1016/j.amjcard.2008.10.033.
  
  Sicari Rosa, Rigo Fausto, Cortigiani Lauro, Gherardi Sonia, Galderisi Maurizio, Picano Eugenio
  
  Abstract
  
  In patients with angiographically normal coronary arteries and chest pain, pharmacologic stress echocardiography can identify a subgroup of patients with a less benign prognosis. Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can currently be combined with wall motion analysis during vasodilator stress echocardiography. The aim of this study was to assess the prognostic value of CFR response in patients with normal coronary arteries and normal wall motion during stress. We selected 394 patients (171 men, 61 +/- 11 years of age) who underwent dipyridamole stress echocardiography (0.84 mg/kg over 6 minutes) with 2-dimensional echocardiography and CFR evaluation of the LAD by Doppler. All had angiographically nonsignificant (
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• Prognostic implications of coronary flow reserve on left anterior descending coronary artery in hypertrophic cardiomyopathy.
  Am J Cardiol

  2008 Dec;102(12):1718-23. doi: 10.1016/j.amjcard.2008.08.023.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  The aim of the study was to prospectively evaluate a cohort of patients with hypertrophic cardiomyopathy (HC) after coronary flow reserve (CFR) assessment of the left anterior descending coronary artery. Sixty-eight patients with HC (40 men, mean +/- SD 58 +/- 12 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) echocardiography with CFR evaluation of the left anterior descending coronary artery by Doppler. Seventy-four age- and gender-matched, apparently healthy subjects served as controls. A CFR value
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• Stress Echocardiography Expert Consensus Statement--Executive Summary: European Association of Echocardiography (EAE) (a registered branch of the ESC).
  Eur Heart J

  2009 Feb;30(3):278-89. doi: 10.1093/eurheartj/ehn492.
  
  Sicari Rosa, Nihoyannopoulos Petros, Evangelista Arturo, Kasprzak Jaroslav, Lancellotti Patrizio, Poldermans Don, Voigt Jens-Uwe, Zamorano Jose Luis,
  
  
  
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• Usefulness of stress echocardiography for risk stratification of patients after percutaneous coronary intervention.
  Am J Cardiol

  2008 Nov;102(9):1170-4. doi: 10.1016/j.amjcard.2008.06.041.
  
  Cortigiani Lauro, Sicari Rosa, Bigi Riccardo, Gherardi Sonia, Rigo Fausto, Gianfaldoni Maria Luisa, Landi Patrizia, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  The prognostic value of stress echocardiography in patients with previous percutaneous coronary intervention (PCI) remains undefined. The aim of this study was to investigate the prognostic implication of stress echocardiography after PCI. The study group comprised 1,063 patients (794 men, 65 +/- 10 years of age) who underwent stress echocardiography with exercise (n = 105), dipyridamole (n = 780), or dobutamine (n = 178) after a median of 10 months from a successful PCI. Of these patients, 616 (58%) complained of chest pain and 447 (42%) were asymptomatic. Stress echocardiogram was positive for inducible ischemia in 328 patients (31%). During a median follow-up of 20 months, there were 167 events (61 deaths, 106 infarctions). Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.09, p
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• The prognostic value of Doppler echocardiographic-derived coronary flow reserve is not affected by concomitant antiischemic therapy at the time of testing.
  Am Heart J

  2008 Sep;156(3):573-9. doi: 10.1016/j.ahj.2008.04.016.
  
  Sicari Rosa, Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Cortigiani Lauro, Picano Eugenio
  
  Abstract
  
  BACKGROUND:
  When wall motion abnormality is the diagnostic end point, concomitant antiischemic therapy heavily modulates the prognostic value of dipyridamole echocardiography test (DET). A negative test result is less benign, and a positive test result is more malignant if performed under therapy. Recently, coronary flow reserve (CFR) was added to wall motion in dual imaging DET. The aim of the study was to determine whether antianginal medications affect the prognostic value of Doppler echocardiographic-derived CFR in patients with known or suspected coronary artery disease undergoing DET.
  
  METHODS:
  In a prospective, multicenter, observational study, we evaluated 1,779 patients (1,072 males; 64 +/- 11 years) who underwent high-dose dipyridamole (0.84 mg/kg for 6 minutes) stress echo with CFR evaluation of left anterior descending (LAD) artery by Doppler.
  
  RESULTS:
  Seven hundred thirty-three (41%) patients were on antiischemic therapy at time of testing (nitrates and/or calcium antagonists and/or beta-blockers). Mean CFR was 2.3. +/- 0.6. At individual patient analysis, 1,141 patients had normal (CFR >2.0) and 638 had abnormal (CFR
  CONCLUSION:
  Ongoing antiischemic therapy at the time of testing does not modulate the prognostic value of Doppler echocardiographic-derived coronary flow reserve.
  
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• Left ventricular ejection fraction measurements: accuracy and prognostic implications in a large population of patients with known or suspected ischemic heart disease.
  Int J Cardiovasc Imaging

  2008 Dec;24(8):793-801. doi: 10.1007/s10554-008-9317-1.
  
  Gimelli Alessia, Landi Patrizia, Marraccini Paolo, Sicari Rosa, Frumento Paolo, L'Abbate Antonio, Rovai Daniele
  
  Abstract
  
  We sought to compare the reliability and prognostic implications of left ventricular (LV) ejection fraction (EF) measurements obtained in routine clinical practice. We retrospectively selected from our clinical database a group of 422 patients with known or suspected ischemic heart disease, studied by two-dimensional echocardiography, gated single-photon emission computed tomography (SPECT) and left ventriculography (LVG) for clinical purposes. In each diagnostic procedure LVEF was measured as done routinely. The LVEF values obtained by the three methods were similar and closely related. The correlation coefficient r was equal to 0.83 between echocardiographic and LVG, to 0.75 between gated SPECT and LVG and to 0.81 between echocardiographic and SPECT. During follow-up (median 41 months), 31 patients died. The values of LVEF obtained by echocardiography, gated-SPECT and LVG were all powerful predictors of all-cause mortality: chi(2) = 12.3 for echocardiography, 14.4 for gated SPECT and 14.5 for LVG. However, including LVEF values into a model based on patient age, sex, history of angina, evidence of previous infarction and number of stenotic coronary arteries, the ability to predict patient survival significantly increased only including LVEF values measured by gated SPECT (chi(2) = 40.6, P = 0.039). Thus, in a large cohort of unselected patients with known or suspected ischemic heart disease, the values of LVEF routinely measured by echocardiography, gated SPECT and LVG were closely correlated, and provided a powerful prognostic information, that was incremental to clinical variables for gated SPECT.
  
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• Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE) (a registered branch of the ESC).
  Eur J Echocardiogr

  2008 Jul;9(4):415-37. doi: 10.1093/ejechocard/jen175.
  
  Sicari Rosa, Nihoyannopoulos Petros, Evangelista Arturo, Kasprzak Jaroslav, Lancellotti Patrizio, Poldermans Don, Voigt Jen-Uwe, Zamorano Jose Luis,
  
  Abstract
  
  Stress echocardiography is the combination of 2D echocardiography with a physical, pharmacological or electrical stress. The diagnostic end point for the detection of myocardial ischemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the potential of adding - coronary flow reserve evaluation of left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage from the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence upon operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of noninvasive diagnosis of coronary artery disease.
  
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• Comparison of prognostic value of pharmacologic stress echocardiography in chest pain patients with versus without diabetes mellitus and positive exercise electrocardiography.
  Am J Cardiol

  2007 Dec;100(12):1744-9.
  
  Cortigiani Lauro, Bigi Riccardo, Sicari Rosa, Rigo Fausto, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  The aim of this study was to compare the prognostic value of pharmacologic stress echocardiography in diabetic and nondiabetic patients with chest pain and intermediate- to high-threshold positive exercise electrocardiographic results. A total of 935 patients with chest pain (131 diabetic patients) with ST-segment depression > or =1 mm on exercise electrocardiography at > or =75-W workload underwent dipyridamole (n = 786) or dobutamine (n = 149) stress echocardiography and were followed up for the occurence of hard (death and infarction) and major events (death, infarction, and late revascularization). During a median follow-up of 26 months, 158 events (51 deaths, 28 myocardial infarctions, and 79 late revascularizations) occurred: 34 in diabetic and 124 in nondiabetic patients (26% vs 15%, p = 0.003). Independent predictors of hard events were age, diabetes, and ischemia at stress echocardiography. Five-year hard event rates were 24% in patients with and 4% in those without ischemia (p
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• The additive prognostic value of wall motion abnormalities and coronary flow reserve during dipyridamole stress echo.
  Eur Heart J

  2008 Jan;29(1):79-88.
  
  Rigo Fausto, Sicari Rosa, Gherardi Sonia, Djordjevic-Dikic Ana, Cortigiani Lauro, Picano Eugenio
  
  Abstract
  
  AIMS:
  The aim of the study was to evaluate the prognostic value of Doppler echocardiographic-derived coronary flow reserve (CFR) over regional wall motion in patients with known or suspected coronary artery disease (CAD) undergoing dipyridamole echocardiography test (DET).
  
  METHODS AND RESULTS:
  In a prospective, multicentre, observational study, we evaluated 1145 patients (702 males; 64 +/- 11 years) who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echo with CFR evaluation of LAD by Doppler. DET was positive for regional wall motion abnormalities in 291 (25%) and negative in 854 (74%) patients. Mean CFR was 2.2 +/- 0.5. At individual patient analysis 702 patients had normal (CFR > 2.0) and 443 had abnormal CFR on LAD. During a median follow-up of 27 months, 109 events occurred: 16 deaths, 17 non-fatal myocardial infarctions, 76 re-hospitalizations for unstable angina. The 30 months infarction-free survival showed the best outcome for those patients with negative DET by wall motion criteria and normal CFR and the worst outcome for patients with positive DET by wall motion and abnormal CFR (99 vs. 68%, P
  CONCLUSION:
  In patients with known or suspected CAD, DET result by wall motion criteria and CFR are additive and complementary for the identification of patients at risk of experiencing hard events.
  
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• Cardiac functional stress imaging: a sequential approach with stress echo and cardiovascular magnetic resonance.
  Cardiovasc Ultrasound

  2007 Dec;5():47.
  
  Sicari Rosa, Pingitore Alessandro, Aquaro Giovanni, Pasanisi Emilio G, Lombardi Massimo, Picano Eugenio
  
  Abstract
  
  AIMS:
  The aim of the study was to assess the feasibility and accuracy of an integrated stress imaging algorithm with echo first and second-line Cardiac Magnetic Resonance (CMR) in selected cases. Stress echo (SE) is widely used for non-invasive diagnosis of coronary artery disease (CAD), but difficult patients and ambiguous responses may be met even with top-level technology and expertise. CMR might ideally complement SE in well-selected cases with unfeasible and/or ambiguous and/or submaximal results.
  
  METHODS AND RESULTS:
  152 in-hospital patients with chest pain and normal baseline function were referred for SE and coronary angiography. Of the initial population, 33 were shunted to CMR due to poor acoustic window or ambiguous or submaximal SE test. The only criterion of positivity for both techniques was the presence of regional wall motion abnormalities in at least 2 contiguous segments. Coronary angiography was performed independently of test results. Significant CAD was identified by a >50% quantitatively assessed diameter reduction in at least 1 major coronary vessel.CAD was present in 88 patients. Interpretable and diagnostic stress test were obtained in 143 patients with the sequential algorithm. The sequential (SE in 110 + CMR in 33 patients) algorithm showed a sensitivity of 76% (95% CI 66% to 85%) specificity of 87% (95% CI 76% to 95%) and accuracy of 80% (95% CI 73% to 86%).
  
  CONCLUSION:
  A sequential functional stress imaging algorithm with stress echo first and stress CMR in selected cases is feasible, clinically realistic and allows an efficient, radiation-free diagnosis of CAD.
  
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• Prognostic value of coronary flow reserve in medically treated patients with left anterior descending coronary disease with stenosis 51% to 75% in diameter.
  Am J Cardiol

  2007 Nov;100(10):1527-31.
  
  Rigo Fausto, Sicari Rosa, Gherardi Sonia, Djordjevic-Dikic Ana, Cortigiani Lauro, Picano Eugenio
  
  Abstract
  
  According to American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 guidelines on percutaneous intervention, intracoronary physiologic measurement in the assessment of effects of intermediate coronary stenoses in patients with anginal symptoms is a class IIa indication. This study assessed the additional prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in patients with single-vessel disease and intermediate stenosis severity. We enrolled 86 patients (44 men; 66 +/- 10 years of age) with angiographically assessed single-vessel coronary artery disease of the left anterior descending coronary artery (LAD) with quantitatively assessed diameter stenosis severity 50% to 75%. All patients underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with wall motion analysis by 2-dimensional echocardiography and CFR evaluation of the affected artery by Doppler. All patients were followed up for a median of 14 months (first quartile 10, third quartile 18) after diagnostic coronary angiography (without percutaneous intervention for a clinically driven decision). Mean diameter stenosis of the LAD was 58 +/- 10%. Mean CFR of the LAD was 2.09 +/- 0.5. Regional wall motion abnormality at peak stress was present in 17 patients. During follow-up, 24 events occurred: 6 nonfatal ST-elevation myocardial infarctions and 18 non-ST-elevation myocardial infarctions. Thirty-month spontaneous event-free survival was higher in patients with normal CFR and lower in patients with decreased CFR (86% vs 30%, p = 0.0001). At Cox analysis, a CFR
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• Additional prognostic value of coronary flow reserve in diabetic and nondiabetic patients with negative dipyridamole stress echocardiography by wall motion criteria.
  J Am Coll Cardiol

  2007 Oct;50(14):1354-61.
  
  Cortigiani Lauro, Rigo Fausto, Gherardi Sonia, Sicari Rosa, Galderisi Maurizio, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  OBJECTIVES:
  The aim of this prospective, multicenter, observational study was to compare the prognostic value of Doppler echocardiographic-derived coronary flow reserve (CFR) in diabetic and nondiabetic patients with known or suspected coronary artery disease and negative dipyridamole stress echocardiography.
  
  BACKGROUND:
  The prognostic value of CFR in diabetic patients with negative stress echocardiography remains unknown.
  
  METHODS:
  The study group consisted of 1,130 patients (207 diabetics) with known (n = 418) or suspected (n = 712) coronary artery disease and negative stress echocardiography by wall motion criteria. All underwent dipyridamole (up to 0.84 mg/kg over 6 min) echocardiography with CFR evaluation of left anterior descending artery by Doppler. A value of CFR
  RESULTS:
  Coronary flow reserve was abnormal in 309 (27%) patients. During a median follow-up of 16 months, 98 events (8 deaths, 24 ST-segment elevation myocardial infarctions, and 66 non-ST-segment elevation myocardial infarctions) occurred. In addition, 101 patients underwent revascularization and were censored. Multivariable prognostic indicators were abnormal CFR (p
  CONCLUSIONS:
  Coronary flow reserve provides independent prognostic information in diabetic and nondiabetic patients with known or suspected coronary artery disease and negative dipyridamole stress echocardiography. In particular, a normal CFR off therapy is associated with better and similar survival in the 2 populations.
  
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• Dobutamine stress echocardiography and the effect of revascularization on outcome in diabetic and non-diabetic patients with chronic ischaemic left ventricular dysfunction.
  Eur J Heart Fail

  2007 Oct;9(10):1038-43.
  
  Cortigiani Lauro, Sicari Rosa, Desideri Alessandro, Bigi Riccardo, Bovenzi Francesco, Picano Eugenio,
  
  Abstract
  
  AIM:
  To evaluate the interaction between prognostic effect of revascularization and viability in diabetic and non-diabetic patients with ischaemic left ventricular dysfunction.
  
  METHODS:
  612 patients with angiographically proven coronary artery disease and left ventricular ejection fraction 0.4). 262 patients (75 diabetics, 187 non-diabetics) underwent revascularization and 350 (88 diabetics, 262 non-diabetics) were on medical therapy.
  
  RESULTS:
  During follow-up 215 patients died. Independent predictors of mortality in revascularized patients were resting left ventricular ejection fraction (HR=0.93, 95% CI 0.89-0.97, p40 (HR=0.44, 95% CI 0.23-0.85, p=0.01), and age (HR=1.03, 95% CI 1.00-1.06, p=0.04). In medically treated patients, independent predictors of mortality were diabetes mellitus (HR=1.64, 95% CI 1.13-2.38, p=0.009), number of diseased vessels (HR=1.27, 95% CI 1.03-1.56, p=0.02), and age (HR=1.02, 95% CI 1.00-1.04, p=0.03). In revascularized patients, 4-year mortality was 15% in those with viability and 26% in those without viability (p=0.04), there was no difference between diabetics and non-diabetics (24% vs 22%; p=0.24).
  
  CONCLUSIONS:
  Viability at dobutamine stress echocardiography independently predicts improved outcome following revascularization in non-diabetics as well as diabetic patients with ischaemic left ventricular dysfunction.
  
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• [Recent advances in the prognostic evaluation of non-ischemic dilated cardiomyopathy].
  Recenti Prog Med

  2007 ;98(7-8):389-97.
  
  Sicari Rosa
  
  Abstract
  
  Heart failure is a progressive syndrome. The rate of deterioration is highly variable and depends on several factors such as the nature and the causes of the overload, and the age of the patient. In general, following a long period of asymptomatic left ventricular (LU) dysfunction, the progression of the disease is rapid once symptoms ensue. Stress echocardiography may play a role both in the early and advanced stages of the disease. In the initial stages a reduced inotropic reserve can unmask initial damage. At advanced stages, stress echocardiography can identify a subgroup of patients at a better outcome despite a similar rest LV function. Protocols and stressors are the conventional ones also applied to patients with known or suspected coronary artery disease. Dipyridamole or dobutamine are able, with an excellent safety profile, to induce a contractile reserve, but the vasodilator stress has the advantage to assess coronary flow reserve, linking the information on function to perfusion. A wide spectrum of echocardiographic parameters is available to the clinical cardiologist assessing the risk of the individual patient. Rest and stress echocardiography are the ideal tool to be applied to this class of patients with dilated cardiomyopathy due to its low cost, widespread availability, lack of ionising radiation and repeatability.
  
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• Prognostic implications of dipyridamole or dobutamine stress echocardiography for evaluation of patients > or =65 years of age with known or suspected coronary heart disease.
  Am J Cardiol

  2007 Jun;99(11):1491-5.
  
  Cortigiani Lauro, Bigi Riccardo, Sicari Rosa, Landi Patrizia, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  This study investigated the value of pharmacologic stress echocardiography for risk stratification of patients > or =65 years of age. The study cohort consisted of 2,160 patients > or =65 years of age (1,257 men, mean +/- SD 71 +/- 5 years of age) undergoing dipyridamole (n = 1,521) or dobutamine (n = 639) stress echocardiography for evaluation of known (n = 913) or suspected (n = 1,247) coronary artery disease. Of 2,160 patients, 753 (35%) had a normal test result, whereas 772 (36%) showed a myocardial ischemic pattern and 635 (29%) a scar pattern. During a median follow-up of 26 months, 241 deaths and 87 nonfatal myocardial infarctions occurred. Patients (n = 568) undergoing revascularization were censored. Of 16 analyzed variables, age (hazard ratio [HR] 1.07 per unit increment), wall motion score index at rest (HR 2.63 per unit increment), ischemia at stress echocardiography (HR 1.81), and diabetes (HR 1.57) were multivariable predictors of death, whereas age (HR 1.06 per unit increment), ischemia at stress echocardiography (HR 2.60), wall motion score index at rest (HR 1.98 per unit increment), scar pattern (HR 1.99), and diabetes (HR 1.48) were multivariable predictors of death or myocardial infarction. Using an interactive stepwise procedure, stress echocardiography showed incremental prognostic value over clinical and echocardiographic data at rest, which decreased with increasing age. In addition, the annual hard event rate associated with a normal test result progressively increased with age. In conclusion, pharmacologic stress echocardiography provides useful prognostic information in patients > or =65 years of age. However, its prognostic value decreases with increasing age.
  
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• Prothrombotic mutations as risk factors for cryptogenic ischemic cerebrovascular events in young subjects with patent foramen ovale.
  Stroke

  2007 Jul;38(7):2070-3.
  
  Botto Nicoletta, Spadoni Isabella, Giusti Sandra, Ait-Ali Lamia, Sicari Rosa, Andreassi Maria Grazia
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Patent foramen ovale (PFO) has been identified as a potential risk factor for cerebrovascular ischemia. Procoagulant mutations may increase the risk and impact the choice of appropriate therapy for secondary prevention. We evaluated the prevalence of the 2 most common genetic risk factors for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young PFO patients who were referred for percutaneous transcatheter closure of their PFO.
  
  METHODS:
  Ninety-seven patients (50 men; mean+/-SD age, 40.9+/-10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; mean+/-SD age, 40.4+/-10.5 years) were recruited into the study. Factor V Leiden and prothrombin G20210A mutations were detected by using a multiplex allele-specific polymerase chain reaction assay.
  
  RESULTS:
  The prevalence of subjects carrying at least 1 prothrombotic genotype was significantly higher in the group of PFO patients than in the group of controls (10.3% vs 2.5%; chi(2)=7.2, P=0.008). Two patients (2.1%) versus 1 control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers for factor V Leiden and prothrombin G20210A mutations, respectively. After adjustment for other vascular risk factors, the combination of either factor V Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI=1.4 to 16.1; P=0.008) increased risk of cerebral ischemia in young patients.
  
  CONCLUSIONS:
  Our results indicate that prothrombotic mutations are important risk factors for cerebral ischemia in young patients with PFO. Screening for thrombotic mutations should be considered in young patients with PFO-related ischemic events.
  
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• The independent prognostic value of contractile and coronary flow reserve determined by dipyridamole stress echocardiography in patients with idiopathic dilated cardiomyopathy.
  Am J Cardiol

  2007 Apr;99(8):1154-8.
  
  Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  The aim of this study was to evaluate the prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in assessing inotropic response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography. All patients had ejection fractions 0.25. All patients were followed for a median of 24 months. Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was 2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p
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• The best of 2005 in echocardiography back from EuroEcho 9--Florence, Italy.
  Cardiovasc Ultrasound

  2006 Feb;4():11.
  
  Sicari Rosa
  
  Abstract
  
  The ninth edition of the congress of the European Association of Echocardiography (EAE) (former working group of Echocardiography) held in Florence has just finished with a great success of participant attendance (2.842) and abstract submissions. Hot topics at EuroEcho 9 were: 1--live 3-dimensional echocardiography and surgical decision making; in pediatric cardiology; in resynchronization therapy 2--stress echocardiography beyond wall motion: from valve diseases to contractility to coronary flow reserve to diastolic function; 3--pulmonary cardiogenic interstitial thickening recognized by ultrasonic lung comets; 4--the "proven clinical inefficacy" of the many technologies sold as breakthrough: color kinesis, tissue characterization, strain rate, tissue Doppler, applied to stress echocardiography.
  
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• The prognostic impact of coronary flow-reserve assessed by Doppler echocardiography in non-ischaemic dilated cardiomyopathy.
  Eur Heart J

  2006 Jun;27(11):1319-23.
  
  Rigo Fausto, Gherardi Sonia, Galderisi Maurizio, Pratali Lorenza, Cortigiani Lauro, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  AIMS:
  Coronary flow-reserve (CFR) can be impaired in non-ischaemic dilated cardiomyopathy (DCM), unmasking a coronary microcirculatory dysfunction of potential prognostic impact. The aim of the present study is to evaluate the prognostic value of Doppler echocardiographic-derived CFR in patients with DCM.
  
  METHODS AND RESULTS:
  We evaluated 129 DCM patients (85 male; age 62+/-11) by transthoracic dipyridamole (0.84 mg/kg in 10 min) stress echocardiography. All patients had an ejection fraction2.0) and 83 had abnormal CFR. During follow-up, 18 patients died and 33 showed worsening of NYHA class. The worse event-free survival was observed in those patients with an abnormal CFR when compared with those having a normal CFR at high dose of dipyridamole (70 vs. 22%, at 75 months of follow-up, P
  CONCLUSION:
  In DCM patients, CFR is often impaired. A reduced CFR during vasodilator stress is an independent prognostic marker of bad prognosis.
  
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• Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.
  J Am Coll Cardiol

  2006 Feb;47(3):605-10.
  
  Cortigiani Lauro, Bigi Riccardo, Sicari Rosa, Landi Patrizia, Bovenzi Francesco, Picano Eugenio
  
  Abstract
  
  OBJECTIVES:
  We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease.
  
  BACKGROUND:
  Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients.
  
  METHODS:
  A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction).
  
  RESULTS:
  During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p
  CONCLUSIONS:
  Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.
  
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• Prognostic value of a multiparametric risk score in patients undergoing dipyridamole stress echocardiography.
  Am J Cardiol

  2005 Aug;96(4):529-32.
  
  Cortigiani Lauro, Bigi Riccardo, Gregori Dario, Sicari Rosa, Picano Eugenio
  
  Abstract
  
  To set up a prognostic score including clinical data and stress echocardiographic findings, the data of 3,969 patients who underwent dipyridamole stress were analyzed. Age (hazard ratio [HR] 3.21), peak wall motion score index (HR 2.62), diabetes mellitus (HR 2.36), and male gender (HR 1.69) were independent predictors of mortality and were incorporated into a prognostic score allowing us to estimate 1-, 3-, and 5-year survival in the patient cohort. The multiparametric risk score, immediately available at the bedside, can be used to predict the survival of patients undergoing dipyridamole stress echocardiography.
  
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• Long-term survival of patients with chest pain syndrome and angiographically normal or near-normal coronary arteries: the additional prognostic value of dipyridamole echocardiography test (DET).
  Eur Heart J

  2005 Oct;26(20):2136-41.
  
  Sicari Rosa, Palinkas Attila, Pasanisi Emilio G, Venneri Lucia, Picano Eugenio
  
  Abstract
  
  AIMS:
  Patients with normal coronary arteries have a heterogeneous prognosis. Aim of this study was to assess whether dipyridamole stress echocardiography positivity identifies a prognostically less benign subset.
  
  METHODS AND RESULTS:
  We selected 457 patients (245 males; 56+/-10 years) who underwent stress high-dose dipyridamole echocardiography and had angiographically non-significant (
  CONCLUSION:
  DET adds incremental value to the prognostic stratification achieved with clinical and angiographic data in the subset of patients with normal or near-normal coronary arteries.
  
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• Relevance of tissue Doppler in the quantification of stress echocardiography for the detection of myocardial ischemia in clinical practice.
  Cardiovasc Ultrasound

  2005 Jan;3():2.
  
  Sicari Rosa
  
  Abstract
  
  In the present article we review the main published data on the application of Tissue Doppler Imaging (TDI) to stress echocardiography for the detection of myocardial ischemia. TDI has been applied to stress echocardiography in order to overcome the limitations of visual analysis for myocardial ischemia. The introduction of a new technology for clinical routine use should pass through the different phases of scientific assessment from feasibility studies to large multicenter studies, from efficacy to effectiveness studies. Nonetheless the pro-technology bias plays a major role in medicine and expensive and sophisticated techniques are accepted before their real usefulness and incremental value to the available ones is assessed. Apparently, TDI is not exempted by this approach : its applications are not substantiated by strong and sound results. Nonetheless, conventional stress echocardiography for myocardial ischemia detection is heavily criticized on the basis of its subjectivity. Stress echocardiography has a long lasting history and the evidence collected over 20 years positioned it as an established tool for the detection and prognostication of coronary artery disease. The quantitative assessment of myocardial ischemia remains a scientific challenge and a clinical goal but time has not come for these newer ultrasonographic techniques which should be restricted to research laboratories.
  
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• Anti-ischemic therapy and stress testing: pathophysiologic, diagnostic and prognostic implications.
  Cardiovasc Ultrasound

  2004 Aug;2():14.
  
  Sicari Rosa
  
  Abstract
  
  Anti-ischemic therapy, in particular beta-blockers, is the most commonly employed drug for the control of myocardial ischemia in patients with stable coronary artery disease. Its widespread use also in patients with suspected coronary artery disease has important practical, clinical diagnostic and prognostic implications because diagnostic tests are heavily influenced by its effects. In the present review, the pathophysiological mechanisms of ischemia protection by antianginal therapy are described. Not all stressors are created equal in front of the different classes of antianginal drugs and on their turn the different classes of drugs exert different levels of protection on inducible ischemia. Several clinical implications can be drawn: From the diagnostic viewpoint antianginal therapy decreases test sensitivity, offsetting the real ischemic burden for a too high percentage of false negative tests. From the prognostic viewpoint test positivity in medical therapy identifies a group of subjects at higher risk of experiencing cardiac death and positivity on medical therapy can be considered a parameter of ischemia severity. Nonetheless in patients with known coronary artery disease the ability of antianginal therapy to modify the ischemic threshold at stress testing represent a powerful means to assess therapy efficacy. From a practical viewpoint, the use of antianginal therapy at time of testing has advantages and disadvantages which are largely dependent on the purpose a test is performed: if the purpose of testing is to diagnose ischemia, it should be performed in the absence of antianginal medications. If the purpose of testing is to assess the protective effects of antianginal therapy, the test should be performed on medications.
  
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• Prognostic value of pharmacological stress echocardiography is affected by concomitant antiischemic therapy at the time of testing.
  Circulation

  2004 May;109(20):2428-31.
  
  Sicari Rosa, Cortigiani Lauro, Bigi Riccardo, Landi Patrizia, Raciti Mauro, Picano Eugenio, ,
  
  Abstract
  
  BACKGROUND:
  The aim of this study was to determine whether antianginal medications affect the prognostic value of pharmacological stress echocardiography.
  
  METHODS AND RESULTS:
  From the EPIC-EDIC Data Bank, 7333 patients (5452 men; age; 59+/-10 years) underwent pharmacological stress echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 minutes; n=4984) or high-dose dobutamine (up to 40 microg x kg(-1) x min(-1); n=2349) (DET) for diagnostic purposes. At the time of testing, 1791 patients were on antiischemic therapy (nitrates and/or calcium antagonists and/or beta-blockers). Patients were followed up for a mean of 2.6 years (range, 1 to 206 months). DET was positive for myocardial ischemia in 2854 patients (39%) and negative in 4479 (61%). Total mortality was 336 (4.5%). Death was attributed to cardiac causes in 161 patients (2.1%). Survival was highest in patients with negative DET off therapy and lowest in patients with positive DET studied on therapy (95% versus 81%; P=0.0000). Survival was comparable in patients with a negative test on therapy and in patients with a positive test off therapy (88% versus 84%, P=NS).
  
  CONCLUSIONS:
  Ongoing antiischemic therapy at the time of testing heavily modulates the prognostic value of pharmacological stress echo. In the presence of concomitant antiischemic therapy, a positive test is more prognostically malignant, and a negative test less prognostically benign.
  
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• Risk stratification by stress echocardiography: a whiter shade of pale?
  Eur J Echocardiogr

  2004 Jun;5(3):162-4.
  
  Picano Eugenio, Sicari Rosa
  
  
  
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• Perioperative risk stratification in non cardiac surgery: role of pharmacological stress echocardiography.
  Cardiovasc Ultrasound

  2004 May;2():4.
  
  Sicari Rosa
  
  Abstract
  
  Perioperative ischemia is a frequent event in patients undergoing major non-cardiac vascular or general surgery. This is in agreement with clinical, pathophysiological, and epidemiological evidence and constitutes an additional diagnostic therapeutic factor in the assessment of these patients. Form a clinical standpoint, it is well known that multidistrict disease, especially at the coronary level, is a severe aggravation of the operative risk. From a pathophysiological point of view, however, surgery creates conditions able to unmask coronary artery disease. Prolonged hypotension, hemorrhages, and haemodynamic stresses caused by aortic clamping and unclamping during major vascular surgery are the most relevant factors endangering the coronary circulation with critical stenoses. From the epidemiological standpoint, coronary disease is known to be the leading cause of perioperative mortality and morbidity following vascular and general surgery: The diagnostic therapeutic corollary of these considerations is that coronary artery disease - and therefore the perioperative risk - in these patients has to be identified in an effective way preoperatively.
  
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• Pharmacologic stress echocardiography predicts total mortality early after acute myocardial infarction.
  J Am Soc Echocardiogr

  2004 Feb;17(2):114-20.
  
  Sicari Rosa, Picano Eugenio, Landi Patrizia, Pasanisi Emilio, Venneri Lucia, ,
  
  Abstract
  
  OBJECTIVE:
  The aim of this multicenter, prospective, observational study was to assess the value of inducible ischemia in a large population of survivors of a first uncomplicated myocardial infarction (MI).
  
  METHODS AND RESULTS:
  Pharmacologic stress echocardiography either with high-dose dipyridamole (0.84 mg/kg over 10 minutes) or high-dose dobutamine (up to 40 microg/kg over 3 minutes) (DET) was performed 9 +/- 10 days after a first acute uncomplicated MI in 1681 patients (1499 males; 57 +/- 10 years) with technically satisfactory rest echocardiographic study. Patients were followed up for a mean of 16 +/- 18 months (range: 1-122). DET was positive for myocardial ischemia in 884 (52.5%) and negative in 797 (47.5%) patients. During the follow-up there were 49 deaths for all-cause mortality (2.9% of the total population), 22 of which were cardiac; 62 (3.6%) nonfatal MIs; and 164 (9.7%) hospital readmissions for unstable angina. In all, 376 patients (22%) underwent coronary revascularization (bypass operation or angioplasty).
  
  RESULTS:
  Hard events occurred in 71 of the 884 patients with positive and in 40 of the 797 patients with negative DET (8% vs 5%, P =.014). Using the Cox proportional hazards model, age (relative risk [RR] 1.07, 95% confidence interval [CI] 1.03-1.1), history of angina (RR 3.8, 95% CI 1.6-8.6), peak wall-motion score index (RR 2.2, 95% CI 1.1-4.4), and pharmacologic dose at ischemia (RR 1.5, 95% CI 1.04-2.3) were independent predictors of all-cause death.
  
  CONCLUSIONS:
  In survivors of a first acute uncomplicated MI DET allows effective risk stratification on the basis of the presence, severity, and extent the induced ischemia.
  
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• Prognostic value of myocardial viability recognized by low-dose dobutamine echocardiography in chronic ischemic left ventricular dysfunction.
  Am J Cardiol

  2003 Dec;92(11):1263-6.
  
  Sicari Rosa, Picano Eugenio, Cortigiani Lauro, Borges Adrian C, Varga Albert, Palagi Caterina, Bigi Riccardo, Rossini Roberta, Pasanisi Emilio,
  
  Abstract
  
  This study assesses the prognostic value of myocardial viability recognized as a contractile response to inotropic stimulation in patients with left ventricular (LV) dysfunction in a large-scale prospective, multicenter, observational study. Four hundred twenty-five patients (mean age 61 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction, and severe LV dysfunction (ejection fraction /=0.40 in WMSI. All patients were followed for a median of 3.1 years. One hundred eighty-eight were revascularized either by coronary artery bypass grafting (n = 118) or coronary angioplasty (n = 70). The only end point analyzed was cardiac death. In the revascularized group, cardiac death occurred in 4 of the 52 patients with and in 37 of the 136 patients without myocardial viability (7.7% vs 27.2%, p
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• Stress echo results predict mortality: a large-scale multicenter prospective international study.
  J Am Coll Cardiol

  2003 Feb;41(4):589-95.
  
  Sicari Rosa, Pasanisi Emilio, Venneri Lucia, Landi Patrizia, Cortigiani Lauro, Picano Eugenio, ,
  
  Abstract
  
  OBJECTIVES:
  The purpose of this study was to assess the long-term value of pharmacologic stress echocardiography with either dipyridamole or dobutamine (DET) for prediction of cardiac death in patients with proven or suspected coronary artery disease (CAD).
  
  BACKGROUND:
  Stress echocardiography is an established, cost-effective technique for the detection of CAD.
  
  METHODS:
  From the Echo Persantine International Cooperative-Echo Dobutamine International Cooperative data bank, 7,333 patients (5,452 males; 59 +/- 10 years) underwent pharmacologic stress echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 min) (n = 4,984) or high-dose dobutamine (up to 40 microg/kg/3 min) (n = 2,349) for diagnostic purposes. Patients were followed up for a mean of 2.6 years (range 1 to 206 months).
  
  RESULTS:
  The DET was positive for myocardial ischemia in 2,854 (35%) patients and negative in 4,479 (61%) patients. During the follow-up there were 161 cardiac deaths (sudden death and fatal myocardial infarction) (2.1% of the total population). Kaplan-Meier survival estimates showed a significantly better outcome for those patients with a negative pharmacologic stress echocardiography test compared with those with a positive test (92 vs. 71.2%, p = 0.0000).
  
  CONCLUSIONS:
  Pharmacologic stress echocardiography with either dipyridamole or dobutamine is effective in predicting cardiac death during a long-term follow-up. A negative stress echocardiography test result is related to a favorable outcome.
  
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• Long-term prognostic value of dipyridamole echocardiography in vascular surgery: a large-scale multicenter study.
  Coron Artery Dis

  2002 Feb;13(1):49-55.
  
  Sicari Rosa, Ripoli Andrea, Picano Eugenio, Pulignano Giovanni, Minardi Giovanni, Rossi Elisabetta, Matskeplishvili Simon,
  
  Abstract
  
  BACKGROUND:
  Late cardiac events after non-cardiac major vascular surgery are an important cause of morbidity and mortality. The aim of the present study was to assess the value of a preoperative dipyridamole echocardiography test (up to 0.84 mg/kg over 10 min) in predicting late cardiac events in survivors of major non-cardiac vascular surgery.
  
  DESIGN:
  Large-scale, multicenter, prospective, observational study design.
  
  METHODS:
  Two hundred and seventy-six patients (mean age 66 +/- 9 years) were studied prior to vascular surgery by dipyridamole stress echocardiography in four different centres. All patients underwent preoperative clinical risk assessment according to the American Heart Association guidelines. All underwent dipyridamole stress echocardiography according to standard high-dose protocol.
  
  RESULTS:
  No major complications occurred during dipyridamole stress echocardiography. Sixty-three patients (23%) had a positive test. Patients were followed up for a median of 20 months. Cardiac events occurred in 43 patients (16%): five deaths, 18 myocardial infarctions and 20 cases of unstable angina. The difference between wall-motion score index (WMSI) at rest and peak stress (delta WMSI), using multivariate analysis, was an independent predictor of late cardiac death.
  
  CONCLUSION:
  Dipyridamole stress echocardiography performed before major vascular surgery identifies patients at high risk for late cardiac events. Stress echocardiographic parameters outperformed clinical variables in the long-term risk stratification in this set of patients.
  
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