Pubblicazioni - Morici Dott.ssa Nuccia

• Validation and additive predictive value of the Academic Research Consortium-High Bleeding Risk Criteria in Older Adults.
  Thromb Haemost

  2020 Dec;():. doi: 10.1055/a-1342-3750.
  
  Montalto Claudio, Crimi Gabriele, Morici Nuccia, Palmerini Tullio, Valgimigli Marco, Savonitto Stefano, De Servi Stefano
  
  Abstract
  
  No Abstract.
  
  Thieme. All rights reserved.
  
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• Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.
  Am Heart J

  2020 Dec;233():39-47. doi: S0002-8703(20)30399-9.
  
  Morici Nuccia, Marini Claudia, Sacco Alice, Tavazzi Guido, Cipriani Manlio, Oliva Fabrizio, Rota Matteo, De Ferrari Gaetano Maria, Campolo Jonica, Frigerio Gianfranco, Valente Serafina, Leonardi Sergio, Corrada Elena, Bottiroli Maurizio, Grosseto Daniele, Cacciavillani Luisa, Frigerio Maria, Pappalardo Federico,
  
  Abstract
  
  BACKGROUND:
  Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap.
  
  METHODS AND DESIGN:
  The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients.
  
  IMPLICATIONS:
  The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.
  
  Copyright © 2020 Elsevier Inc. All rights reserved.
  
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• Home-based COVID 19 management: A consensus document from Italian general medical practitioners and hospital consultants in the Lombardy region (Italy).
  Eur J Intern Med

  2020 Dec;():. doi: S0953-6205(20)30443-X.
  
  Morici Nuccia, Puoti Massimo, Zocchi Maria Teresa, Brambilla Carla, Mangiagalli Andrea, Savonitto Stefano
  
  
  
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• Bleeding risk prediction in elderly patients managed invasively for acute coronary syndromes: External validation of the PRECISE-DAPT and PARIS scores.
  Int J Cardiol

  2020 Dec;():. doi: S0167-5273(20)34234-0.
  
  Montalto Claudio, Crimi Gabriele, Morici Nuccia, Piatti Luigi, Grosseto Daniele, Sganzerla Paolo, Tortorella Giovanni, De Rosa Roberta, De Luca Leonardo, De Luca Giuseppe, Palmerini Tullio, Valgimigli Marco, Savonitto Stefano, De Servi Stefano
  
  Abstract
  
  BACKGROUND:
  We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management.
  
  METHODS:
  Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials.
  
  RESULTS:
  After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3-5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all ? > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%.
  
  CONCLUSIONS:
  In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak.
  ESC Heart Fail

  2020 Oct;():. doi: 10.1002/ehf2.13043.
  
  Severino Paolo, D'Amato Andrea, Saglietto Andrea, D'Ascenzo Fabrizio, Marini Claudia, Schiavone Marco, Ghionzoli Nicolò, Pirrotta Filippo, Troiano Francesca, Cannillo Margherita, Mennuni Marco, Rognoni Andrea, Rametta Francesco, Galluzzo Alessandro, Agnes Gianluca, Infusino Fabio, Pucci Mariateresa, Lavalle Carlo, Cacciotti Luca, Mather Paul J, Grosso Marra Walter, Ugo Fabrizio, Forleo Giovanni, Viecca Maurizio, Morici Nuccia, Patti Giuseppe, De Ferrari Gaetano M, Palazzuoli Alberto, Mancone Massimo, Fedele Francesco
  
  Abstract
  
  AIMS:
  The recent coronavirus disease 19 (COVID-19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID-19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year.
  
  METHODS AND RESULTS:
  We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter-year period (21 February to 31 March 2019) and an intra-year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra-year period, and 192 during inter-year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra-year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56-0.89; P = 0.0037), or with inter-year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45-0.72; P < 0.001). Patients admitted during study period were less frequently admitted in New York Heart Association (NYHA) Class II compared with inter-year period (P = 0.019). At covariance analysis NYHA class was significantly lower in patients admitted during inter-year control period, compared with patients admitted during case period (P = 0.014).
  
  CONCLUSIONS:
  Admissions for HF were significantly reduced during the lockdown due to the COVID-19 pandemic in Italy.
  
  © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
  
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• Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration.
  J Thromb Haemost

  2020 11;18(11):2958-2967. doi: 10.1111/jth.15094.
  
  Tritschler Tobias, Mathieu Marie-Eve, Skeith Leslie, Rodger Marc, Middeldorp Saskia, Brighton Timothy, Sandset Per Morten, Kahn Susan R, Angus Derek C, Blondon Marc, Bonten Marc J, Cattaneo Marco, Cushman Mary, Derde Lennie P G, DeSancho Maria T, Diehl Jean-Luc, Goligher Ewan, Jilma Bernd, Jüni Peter, Lawler Patrick R, Marietta Marco, Marshall John C, McArthur Colin, Miranda Carlos Henrique, Mirault Tristan, Morici Nuccia, Perepu Usha, Schörgenhofer Christian, Sholzberg Michelle, Spyropoulos Alex C, Webb Steve A, Zarychanski Ryan, Zuily Stéphane, Le Gal Grégoire,
  
  Abstract
  
  INTRODUCTION:
  Coronavirus disease (COVID-19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal dose of anticoagulant intervention in hospitalized patients with COVID-19 and consequently, immediate answers from high-quality randomized trials are needed.
  
  METHODS:
  The World Health Organization's International Clinical Trials Registry Platform was searched on June 17, 2020 for randomized controlled trials comparing increased dose to standard dose anticoagulant interventions in hospitalized COVID-19 patients. Two authors independently screened the full records for eligibility and extracted data in duplicate.
  
  RESULTS:
  A total of 20 trials were included in the review. All trials are open label, 5 trials use an adaptive design, 1 trial uses a factorial design, 2 trials combine multi-arm parallel group and factorial designs in flexible platform trials, and at least 15 trials have multiple study sites. With individual target sample sizes ranging from 30 to 3000 participants, the pooled sample size of all included trials is 12 568 participants. Two trials include only intensive care unit patients, and 10 trials base patient eligibility on elevated D-dimer levels. Therapeutic intensity anticoagulation is evaluated in 14 trials. All-cause mortality is part of the primary outcome in 14 trials.
  
  DISCUSSION:
  Several trials evaluate different dose regimens of anticoagulant interventions in hospitalized patients with COVID-19. Because these trials compete for sites and study participants, a collaborative effort is needed to complete trials faster, conduct pooled analyses and bring effective interventions to patients more quickly.
  
  © 2020 International Society on Thrombosis and Haemostasis.
  
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• Arterial elastance modulation by intra-aortic balloon counterpulsation in patients with acute decompensated heart failure and low-output state.
  J Cardiovasc Med (Hagerstown)

  2020 Aug;():. doi: 10.2459/JCM.0000000000001088.
  
  Sacco Alice, Tavazzi Guido, Morici Nuccia, Viola Giovanna, Meani Paolo, Oliva Fabrizio G, Pappalardo Federico
  
  Abstract
  
  : Heart failure is characterized by ventriculo-arterial decoupling which decreases myocardial efficiency and is exacerbated by tachycardia and by increased total peripheral resistance that worsen static arterial elastance; unlike aortic pressure by itself, this measure is independent of the function of the ventricle. Therefore, it is an index which describes arterial properties.We investigated the effect of intra-aortic balloon counterpulsation on arterial elastance, a variable which can be obtained non-invasively, in patients with acute decompensated heart failure deteriorated in low output state.17 out of 24 patients admitted for acute decompensated heart failure underwent intra-aortic balloon counterpulsation insertion for hemodynamic worsening condition despite medical therapy.Hemodynamic variables were obtained with a pulmonary artery catheter; arterial elastance and cardiac power index were calculated.Intra-aortic balloon counterpulsation was associated with a decrease of the arterial elastance median value (1.64 vs. 1.28?mmHg/ml- P?=?0.04) along withan increase in cardiac power index (0.29, vs 0.40, W/m; P?=?0.02 ). Mixed venous saturation (53?mmHg, vs 70?mmHg; P?=?0.007) and pulmonary mean arterial pressure (41 vs 30?mmHg; P?=?0.005) significantly changed after intraortic balloon counterpulsation insertion. No significant changes in heart rate (median 80, vs 80, bpm; P?=?0.809) were observed.Intraortic balloon counterpulsation may effectively improve arterial elastance on top of a conservative use of inotropes/vasopressors, with a significant improvement in hemodynamics.
  
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• Optimal P2Y12 inhibition in older adults with acute coronary syndromes: A network meta-analysis of randomized controlled trials.
  Eur Heart J Cardiovasc Pharmacother

  2020 Aug;():. doi: pvaa101.
  
  Montalto Claudio, Morici Nuccia, Munafò Andrea Raffaele, Mangieri Antonio, Mandurino-Mirizzi Alessandro, D'Ascenzo Fabrizio, Oreglia Jacopo, Latib Azeem, Porto Italo, Colombo Antonio, Savonitto Stefano, De Servi Stefano, Crimi Gabriele
  
  Abstract
  
  AIMS:
  Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischemic and bleeding endpoints in older adults with ACS.
  
  METHODS AND RESULTS:
  Randomized clinical trials that reported separately the results of adults older >70 years for at least the primary endpoint (composite of death, myocardial infarction [MI] and stroke). Seven studies (14,485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischemic endpoint (composite of MI and stroke) and was most likely the best treatment (Surface Under the Cumulative Ranking curve Analysis [SUCRA] 54.5 and 59.8, respectively). With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%) while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA.
  
  CONCLUSION:
  Among older subjects with ACS, DAPT should be balanced upon ischemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults.
  
  © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: journals.permissions@oup.com.
  
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• Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome.
  Eur J Intern Med

  2020 Dec;82():62-67. doi: S0953-6205(20)30296-X.
  
  Centola Marco, Maloberti Alessandro, Castini Diego, Persampieri Simone, Sabatelli Ludovico, Ferrante Giulia, Lucreziotti Stefano, Morici Nuccia, Sacco Alice, Oliva Fabrizio, Rebora Paola, Giannattasio Cristina, Mafrici Antonio, Carugo Stefano
  
  Abstract
  
  BACKGROUND:
  To assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score).
  
  METHODS:
  The data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed.
  
  RESULTS:
  1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60-78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33-2.22, p < 0.0001) and GRACE score (OR 1.04 95%CI 1.02-1.06, p < 0.0001) were significantly associated with an increased risk of in-hospital death at the multivariate analysis. Admission values of SUA were stratified in four quartiles. Rates of acute kidney injury, implantation of intra-aortic balloon pump and non-invasive ventilation use were significantly higher in the last quartile compared to Q1, Q2 and Q3 (p < 0.01). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89-0.93, p < 0.0001) and 0.79 (95% CI 0.76-0.81, p < 0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93-0.95).
  
  CONCLUSIONS:
  High admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population.
  
  Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome.
  CJC Open

  2020 Jul;2(4):236-243. doi: 10.1016/j.cjco.2020.03.005.
  
  Morici Nuccia, Alicandro Gianfranco, Ferri Luca A, Piatti Luigi, Grosseto Daniele, Sganzerla Paolo, Tortorella Giovanni, Ferrario Maurizio, Crimi Gabriele, Bossi Irene, Tondi Stefano, Petronio Anna Sonia, Mariani Matteo, Toso Anna, Ravera Amelia, Corrada Elena, Cao Davide, Di Ascenzo Leonardo, La Vecchia Carlo, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  Background:
  The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual ergy Between Percutaneous Coronary Intervention With us and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events.
  
  Methods:
  A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS.
  
  Results:
  Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit.
  
  Conclusions:
  In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.
  
  © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.
  
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• Long-Term Risk of Major Adverse Cardiovascular Events in Patients With Acute Coronary Syndrome: Prognostic Role of Complete Blood Cell Count.
  Angiology

  2020 10;71(9):831-839. doi: 10.1177/0003319720938619.
  
  Morici Nuccia, Molinari Valentina, Cantoni Silvia, Rubboli Andrea, Antolini Laura, Sacco Alice, Cattaneo Marco, Alicandro Gianfranco, Oreglia Jacopo A, Oliva Fabrizio, Giannattasio Cristina, Brunelli Dario, La Vecchia Carlo, Valgimigli Marco, Savonitto Stefano
  
  Abstract
  
  Individual parameters of complete blood count (CBC) have been associated with worse outcome in patients with acute coronary syndrome (ACS). However, the prognostic role of CBC taken as a whole has never been evaluated for long-term incidence of major adverse cardiovascular events (MACEs). Patients were grouped according to their hematopoietic cells' inflammatory response at different time points during hospital stay. Patients with admission white blood cell count >10 × 10/L, discharge hemoglobin <120 g/L, and discharge platelet count >250 × 10/L were defined as "high-risk CBC." Among 1076 patients with ACS discharged alive, 129 (12%) had a "high-risk CBC" and 947 (88%) had a "low-risk CBC." Patients with "high-risk CBC" were older and had more comorbidities. Over a median follow-up of 665 days, they experienced a higher incidence of MACE compared to "low-risk CBC" patients (18.6% vs 8.1%). After adjustment for age, age-adjusted Charlson comorbidity index, female sex, cardiac arrest, suboptimal discharge therapy, coronary artery bypass, and ejection fraction, a high-risk CBC was significantly associated with increased MACE occurrence (adjusted hazard ratio 1.80; 95% CI: 1.09-3.00). The CBC was a prognostic marker in patients with ACS, and its evaluation at admission and discharge could better classify patient's risk and improve therapeutic management.
  
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• Role of von Willebrand Factor and ADAMTS-13 in the Pathogenesis of Thrombi in SARS-CoV-2 Infection: Time to Rethink.
  Thromb Haemost

  2020 09;120(9):1339-1342. doi: 10.1055/s-0040-1713400.
  
  Morici Nuccia, Bottiroli Maurizio, Fumagalli Roberto, Marini Claudia, Cattaneo Marco
  
  
  
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• Clinical Impact of Valvular Heart Disease in Elderly Patients Admitted for Acute Coronary Syndrome: Insights From the Elderly-ACS 2 Study.
  Can J Cardiol

  2020 Jul;36(7):1104-1111. doi: S0828-282X(19)31439-4.
  
  Crimi Gabriele, Montalto Claudio, Ferri Luca Angelo, Piatti Luigi, Bossi Irene, Morici Nuccia, Mandurino-Mirizzi Alessandro, Grosseto Daniele, Tortorella Giovanni, Savonitto Stefano, De Servi Stefano,
  
  Abstract
  
  BACKGROUND:
  Elderly patients are under-represented in clinical trials and registries, and a gap of evidence exists for clinical decision making in the setting of acute coronary syndromes (ACS). We aimed to assess the prevalence and independent prognostic impact of valvular heart disease (VHD) diagnosed during the index hospitalization on clinical outcomes among elderly patients with ACS. Included VHDs were moderate-to-severe mitral regurgitation (MR), moderate-to-severe aortic stenosis (AS), or both combined.
  
  METHODS:
  We explored the Elderly-ACS 2 dataset, which includes patients older than 74 years of age diagnosed with ACS and managed invasively. The primary endpoint was a composite of all-cause death, myocardial infarction, disabling stroke, and rehospitalization for heart failure at 1 year; the secondary endpoint was death for cardiovascular causes. Patients were stratified into 4 groups: no VHD, moderate-to-severe MR, moderate-to-severe AS, and both moderate-to-severe MR and AS.
  
  RESULTS:
  Of the 1443 subjects enrolled, 190 (13.2%) had moderate-to-severe MR, 26 (1.8%) had moderate-to-severe AS, and 13 (0.9%) had both moderate-to-severe MR and AS. When compared with those with no VHD, patients with moderate-to-severe MR had hazard ratios (HRs) for the primary endpoint of 2.04 (95% confidence interval [CI], 1.36-3.07], those with moderate-to-severe AS had HRs of 3.10 (95% CI, 1.39-6.93), and those with both moderate-to-severe MR and AS had HRs of 4.00 (95% CI, 1.65-9.73] (all P < 0.01). Patients with moderate-to-severe MR also had increased risks of cardiovascular death (HR 3.17; 95% CI, 1.57-6.42; P < 0.01), whereas in those with moderate-to-severe AS or both moderate-to-severe MR and AS, a nonsignificant increased risk was observed.
  
  CONCLUSIONS:
  In a contemporary cohort of elderly patients admitted for ACS, VHD was found in 1 of 5 subjects and had an independent, consistent impact on prognosis.
  
  Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
  
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• Is thromboprophylaxis with high-dose enoxaparin really necessary for COVID-19 patients? A new "prudent" randomised clinical trial.
  Blood Transfus

  2020 05;18(3):237-238. doi: 10.2450/2020.0109-20.
  
  Cattaneo Marco, Morici Nuccia
  
  
  
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• Impact of renal dysfunction and acute kidney injury on outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention.
  Eur Heart J Acute Cardiovasc Care

  2020 May;():2048872620920475. doi: 10.1177/2048872620920475.
  
  De Rosa Roberta, Morici Nuccia, De Servi Stefano, De Luca Giuseppe, Galasso Gennaro, Piscione Federico, Ferri Luca A, Piatti Luigi, Grosseto Daniele, Tortorella Giovanni, Franco Nicoletta, Lenatti Laura, Misuraca Leonardo, Leuzzi Chiara, Verdoia Monica, Sganzerla Paolo, Cacucci Michele, Ferrario Maurizio, Murena Ernesto, Sibilio Gerolamo, Toso Anna, Savonitto Stefano
  
  Abstract
  
  BACKGROUND:
  Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities.
  
  AIM:
  The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention.
  
  METHODS:
  Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age)?×?body weight?×?0.85 if female]/(72?×?serum creatinine)* 1.73 m of body surface area), patients were classified as having none or mild (eGFR ?60?ml/min/1.73 m), moderate (eGFR 30-59?ml/min/1.73 m) or severe (eGFR <30?ml/min/1.73 m) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months.
  
  RESULTS:
  A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (?
  CONCLUSIONS:
  Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.
  
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• Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.
  J Cardiovasc Med (Hagerstown)

  2020 Jun;21(6):453-459. doi: 10.2459/JCM.0000000000000978.
  
  De Luca Giuseppe, Verdoia Monica, Savonitto Stefano, Piatti Luigi, Grosseto Daniele, Morici Nuccia, Bossi Irene, Sganzerla Paolo, Tortorella Giovanni, Cacucci Michele, Murena Ernesto, Toso Anna, Bongioanni Sergio, Ravera Amelia, Corrada Elena, Mariani Matteo, Di Ascenzo Leonardo, Petronio Anna S, Cavallini Claudio, Vitrella Giancarlo, Antonicelli Roberto, Rogacka Renata, De Servi Stefano,
  
  Abstract
  
  BACKGROUND:
  Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy.
  
  METHODS:
  Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission.
  
  RESULTS:
  Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P?=?0.01) more extensive coronary disease (P?=?0.02), more advanced Killip class at presentation (P?=?0.003), use at admission of statins (P?=?0.004) and diuretics at discharge (P?
  CONCLUSION:
  Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.
  
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• Risk stratification vs routine intensive care stay in non ST segment elevation myocardial infarction (NSTEMI).
  Eur J Intern Med

  2020 06;76():26-27. doi: S0953-6205(20)30126-6.
  
  Savonitto Stefano, Morici Nuccia
  
  
  
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• Characteristics and Outcome of Patients ?75 Years of Age With Prior Coronary Artery Bypass Grafting Admitted for an Acute Coronary Syndrome.
  Am J Cardiol

  2020 06;125(12):1788-1793. doi: S0002-9149(20)30270-8.
  
  Morici Nuccia, De Rosa Roberta, Crimi Gabriele, De Luca Leonardo, Ferri Luca A, Lenatti Laura, Piatti Luigi, Tortorella Giovanni, Grosseto Daniele, Franco Nicoletta, Bossi Irene, Montalto Claudio, Antonicelli Roberto, Alicandro Gianfranco, De Luca Giuseppe, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  The prognostic role of previous coronary artery bypass (CABG) in elderly patients admitted to hospital for an acute coronary syndrome (ACS) is unclear. Therefore, the aim of this study was to compare the prognosis of patients aged ?75 years admitted for an ACS with or without previous history of CABG. The primary outcome of the study was a composite of overall mortality, recurrent nonfatal myocardial infarction, nonfatal stroke, and rehospitalization for heart failure at 1-year follow-up. We included 2,253 ACS patients, aged 81 (78 to 85) years enrolled in 3 multicenter studies (the Italian Elderly ACS study, the LADIES ACS study, and the Elderly ACS 2 randomised trial) - 178 (7.9%) with previous CABG, 2,075 (92.1%) without. Patients with previous CABG had a higher burden of cardiovascular risk factors, lower ejection fraction, and higher creatinine values on admission. However, both at univariate analysis and after adjustment for the most relevant covariates (sex, age, previous myocardial infarction, type of ACS, left ventricular ejection fraction, and serum creatinine on admission), previous CABG did not show any statistically significant association with 1-year outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.61 to 1.19; p?=?0.353). In conclusion, our study suggests that elderly ACS patients with previous CABG have worse basal clinical characteristics. Nevertheless, in a broad cohort of patients mostly treated with percutaneous coronary intervention during the index event, previous CABG did not confer independent additional risk of major adverse cardiovascular events at 1-year follow-up.
  
  Copyright © 2020 Elsevier Inc. All rights reserved.
  
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• Impact of body mass index on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: Insights from the ELDERLY ACS 2 trial.
  Nutr Metab Cardiovasc Dis

  2020 05;30(5):730-737. doi: S0939-4753(20)30017-X.
  
  De Luca Giuseppe, Verdoia Monica, Savonitto Stefano, Ferri Luca A, Piatti Luigi, Grosseto Daniele, Morici Nuccia, Bossi Irene, Sganzerla Paolo, Tortorella Giovanni, Cacucci Michele, Ferrario Maurizio, Murena Ernesto, Sibilio Girolamo, Tondi Stefano, Toso Anna, Bongioanni Sergio, Ravera Amelia, Corrada Elena, Mariani Matteo, Di Ascenzo Leonardo, Petronio A Sonia, Cavallini Claudio, Vitrella Giancarlo, Antonicelli Roberto, Rogacka Renata, De Servi Stefano,
  
  Abstract
  
  BACKGROUND AND AIM:
  Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS.
  
  METHODS AND RESULTS:
  Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (
  CONCLUSIONS:
  Among elderly patients with ACS, BMI did not condition the survival or the risk of major cardiovascular and bleeding complications. The results were consistent across several patient risk categories.
  
  Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  
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• De-escalating dual antiplatelet therapy in patients with acute coronary syndromes: the right strategy to harmonize time-dependent ischemic and bleeding risk in elderly patients?
  J Cardiovasc Med (Hagerstown)

  2020 Apr;21(4):281-285. doi: 10.2459/JCM.0000000000000929.
  
  Crimi Gabriele, De Rosa Roberta, Mandurino-Mirizzi Alessandro, Morici Nuccia, Alberti Luca Paolo, Savonitto Stefano, De Servi Stefano
  
  Abstract
  
  : The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge.
  
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• Cangrelor use in a 6-year-old patient undergoing complex percutaneous coronary intervention after post-surgical myocardial infarction.
  Platelets

  2020 Nov;31(8):1090-1093. doi: 10.1080/09537104.2020.1732323.
  
  Sirico Domenico, Morici Nuccia, Soriano Francesco, Marianeschi Stefano Maria, Pedrazzini Giovanna, Leonardi Sergio, Vignati Gabriele
  
  Abstract
  
  Cangrelor is an intravenously administered P2Y receptor antagonist, which has been approved for adult patients undergoing percutaneous coronary intervention and, due to its unique pharmacokinetics, it allows effective and controllable peri-procedural platelet inhibition. We report the case of a 6-year-old child with anomalous origin of right coronary artery from aortic left coronary sinus, who underwent elective surgical replacement of stenotic and calcified conduit between the right ventricle and the main pulmonary artery. The surgery was complicated by acute myocardial infarction secondary to coronary extrinsic compression. The patient was successfully treated with urgent percutaneous coronary intervention (simultaneous V-stenting) and cangrelor infusion, subsequently switched to clopidogrel therapy.
  
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• Lipid Lowering Treatment and Eligibility for PCSK9 Inhibition in Post-Myocardial Infarction Patients in Italy: Insights from Two Contemporary Nationwide Registries.
  Cardiovasc Ther

  2020 ;2020():3856242. doi: 10.1155/2020/3856242.
  
  Colivicchi Furio, Massimo Gulizia Michele, Arca Marcello, Luigi Temporelli Pier, Gonzini Lucio, Venturelli Vanessa, Morici Nuccia, Indolfi Ciro, Gabrielli Domenico, De Luca Leonardo
  
  Abstract
  
  Introduction:
  The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known.
  
  Methods:
  Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70?mg/dl; 70-99?mg/dl and ?100?mg/dl.
  
  Results:
  Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C?
  Conclusions:
  Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria.
  
  Copyright © 2020 Furio Colivicchi et al.
  
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• [Relevance of complete blood count parameters in the assessment of acute coronary syndromes: a combined hematological and cardiological perspective].
  G Ital Cardiol (Rome)

  2019 Dec;20(12):694-705. doi: 10.1714/3271.32379.
  
  Morici Nuccia, Cantoni Silvia, Soriano Francesco, Viola Giovanna, De Stefano Valerio, Veas Nicolas, Oreglia Jacopo A, Esposito Giuseppe, Sacco Alice, Savonitto Stefano
  
  Abstract
  
  The aim of this review is to explore the available evidence concerning the relationship between the different parameters of the complete blood count, its pathophysiological changes and cardiovascular disease, specifically focusing on the acute ischemic setting. Erythrocytes, leukocytes and platelets undergo significant and more or less durable changes over time in response to conditions of systemic inflammatory, infectious and neoplastic disease. This is the reason why blood cell count parameters can (and should) be implemented in the global assessment of the patient with acute coronary syndrome.From the literature review it emerges that anemia and thrombocytopenia have an independent negative prognostic role in the medium and long term, being markers of the overall frailty of patients with ischemic heart disease. On the other hand, essential thrombocythemia and polycythemia vera, two chronic myeloproliferative neoplasms, are characterized by an important increase in thrombotic risk. Both conditions are given a brief description for the particular importance of the close collaboration between cardiologists and hematologists in the diagnosis and treatment of these diseases in the context of ischemic heart disease.
  
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• Assessing bleeding in acute coronary syndrome using the Bleeding Academic Research Consortium definition.
  J Cardiovasc Med (Hagerstown)

  2019 Dec;20(12):818-824. doi: 10.2459/JCM.0000000000000888.
  
  Fortuni Federico, Crimi Gabriele, Morici Nuccia, De Luca Giuseppe, Alberti Luca Paolo, Savonitto Stefano, De Servi Stefano
  
  Abstract
  
  BACKGROUND:
  The Bleeding Academic Research Consortium (BARC) definition was proposed to overcome the heterogeneity among the many bleeding definitions. The aim of this study-level meta-analysis was to explore the incidence of BARC-assessed bleeding in acute coronary syndrome (ACS) studies and to ascertain the relation between these events and variables related to bleeding risk.
  
  METHODS AND RESULTS:
  We searched the literature for studies that reported bleeding events according to BARC criteria in ACS patients. An analysis on heterogeneity between studies in bleeding reports was performed with I test. A meta-regression was conducted to explore the relation between different types of BARC bleedings and patient and procedural features. Nine studies were included in the analysis. Overall, BARC 2 rates were higher than BARC 3 or 5 rates (6.3 versus 2.6%). An extremely high level of heterogeneity was detected both for BARC 2 (I 99.3%) and BARC 3 or 5 (I 97.5%) bleedings. Increasing age [? coefficient 0.4% (0.2-0.6%); P?
  CONCLUSION:
  The high level of heterogeneity in BARC bleeding reports only partially explained by bleeding risk profile suggests that a regulatory guidance to properly evaluate bleedings and to estimate the risk--benefit in clinical trials investigating different antithrombotic treatments in ACS patients is needed.
  
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• Recurrent stent thrombosis in a patient with acute coronary syndrome and ischemic colitis: between life-threatening thrombosis and life-threatening bleeding.
  Platelets

  2020 Aug;31(6):820-824. doi: 10.1080/09537104.2019.1678122.
  
  Morici Nuccia, Cantoni Silvia, Soriano Francesco, Sacco Alice, Viola Giovanna, Esposito Giuseppe, Oreglia Jacopo A, Cattaneo Marco, Savonitto Stefano
  
  Abstract
  
  Complete blood count should always be considered to tailor diagnosis and appropriate management in patients with acute ischemic heart disease. We present a challenging case of recurrent acute coronary syndrome, in the context of very high thrombotic risk due to concomitant inflammatory disease. Although no general guidelines exist for the switch between antiplatelet agents, particularly in the acute setting, in specific cases, the availability of different orally- and i.v.-acting agents and platelet function tests may allow to discriminate among multiple possible mechanisms of drug failure or side effects in the individual patient.
  
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• Cangrelor bridging strategy for liver damage after mechanical chest compression.
  Anatol J Cardiol

  2019 Sep;22(4):E8-E9. doi: 10.14744/AnatolJCardiol.2019.78546.
  
  Cereda Alberto Francesco, Morici Nuccia, Aseni Paolo, Chiara Osvaldo
  
  
  
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• Fifteen-Year Trends of Cardiogenic Shock and Mortality in Patients with Diabetes and Acute Coronary Syndromes.
  Am J Med

  2020 03;133(3):331-339.e2. doi: S0002-9343(19)30688-6.
  
  Dauriz Marco, Morici Nuccia, Gonzini Lucio, Lucci Donata, Di Chiara Antonio, Boccanelli Alessandro, Olivari Zoran, Casella Gianni, De Luca Leonardo, Temporelli Pierluigi, De Servi Stefano, Bonora Enzo, Savonitto Stefano
  
  Abstract
  
  PURPOSE:
  Our study was intended to examine time trends of management and mortality of acute coronary syndrome patients with associated diabetes mellitus.
  
  METHODS:
  We analyzed data from 5 nationwide registries established between 2001 and 2014, including consecutive acute coronary syndrome patients admitted to the Italian Intensive Cardiac Care Units.
  
  RESULTS:
  Of 28,225 participants, 8521 (30.2%) had diabetes: as compared with patients without diabetes, they were older and had significantly higher rates of prior myocardial infarction and comorbidities (all P < .0001). Prevalence of diabetes and comorbidities increased over time (P for trend < .0001). Cardiogenic shock rates were higher in patients with diabetes, as compared with those without diabetes (7.8% vs 2.8%, P < .0001), and decreased significantly over time only in patients without diabetes (P = .007). Revascularization rates increased over time in patients both with and without diabetes (both P for trend < .0001), although with persistingly lower rates in patients with diabetes. All-cause in-hospital mortality was higher in patients with diabetes (5.4 vs 2.5%, respectively, P < .0001) and decreased more consistently in patients without diabetes (P for trend = .007 and < .0001, respectively). At multivariable analysis, diabetes remains an independent predictor of both cardiogenic shock (odds ratio 2.03; 95% confidence interval, 1.77-2.32; P < .0001) and mortality (odds ratio 1.95; 95% confidence interval, 1.69-2.26; P < .0001).
  
  CONCLUSIONS:
  Despite significant mortality reductions observed over 15 years in acute coronary syndromes, patients with diabetes continue to show threefold higher rates of cardiogenic shock and lower revascularization rates as compared with patients without diabetes. These findings may explain the persistingly higher mortality of patients with diabetes and acute coronary syndromes.
  
  Copyright © 2019 Elsevier Inc. All rights reserved.
  
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• Getting to the heart of the matter in a multisystem disorder: Erdheim-Chester disease.
  Lancet

  2019 Aug;394(10198):e19. doi: S0140-6736(19)31787-8.
  
  Buono Andrea, Bassi Ilaria, Santolamazza Caterina, Moreo Antonella, Pedrotti Patrizia, Sacco Alice, Morici Nuccia, Giannattasio Cristina, Oliva Fabrizio, Ammirati Enrico
  
  
  
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• Use of Clinical Risk Score in an Elderly Population: Need for Ad Hoc Validation and Calibration.
  J Am Coll Cardiol

  2019 07;74(1):161-162. doi: S0735-1097(19)35105-8.
  
  Montalto Claudio, Crimi Gabriele, Morici Nuccia, Savonitto Stefano, De Servi Stefano
  
  
  
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• Use of PRECISE-DAPT Score and Admission Platelet Count to Predict Mortality Risk in Patients With Acute Coronary Syndrome.
  Angiology

  2019 Oct;70(9):867-877. doi: 10.1177/0003319719848547.
  
  Morici Nuccia, Tavecchia Giovanni A, Antolini Laura, Caporale Maria R, Cantoni Silvia, Bertuccio Paola, Sacco Alice, Meani Paolo, Viola Giovanna, Brunelli Dario, Oliva Fabrizio, Lombardi Federico, Segreto Antonio, Oreglia Jacopo A, La Vecchia Carlo, Cattaneo Marco, Valgimigli Marco, Savonitto Stefano
  
  Abstract
  
  The PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy (PRECISE-DAPT) score has been validated to predict bleeding complications in patients undergoing stent implantation and dual antiplatelet therapy. This score does not include the platelet count (PC), which has been shown to be an independent marker of mortality in patients with acute coronary syndrome (ACS). We assessed the role of the PRECISE-DAPT score calculated on admission for mortality risk prediction and evaluated whether the predictive accuracy of this score improved by adding the PC. In a retrospective cohort study of 1000 patients with ACS, after adjustment for relevant covariates, a PRECISE-DAPT score ?25 was independently associated with mortality (hazard ratio [HR]: 7.91; 95% confidence interval [CI]: 4.37-14.30). When this score was combined with PC, compared to patients with PRECISE-DAPT <25 and PC ?150 × 10/L, the adjusted HR was 7.2 (95% CI 2.4-21.6) for those with PRECISE-DAPT <25 and PC <150 × 10/L; 10.7 (95% CI: 5.2-21.9) for those with PRECISE-DAPT ?25 and PC ?150 × 10/L; and 17.9 (95% CI 7.0-45.4) for those with PRECISE-DAPT ?25 and PC <150 × 10/L. Selecting thresholds for high-risk designation, the PRECISE-DAPT score integrated with PC had a higher prediction value, compared to the PRECISE-DAPT and Global Registry of Acute Coronary Events scores.
  
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• Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?
  Platelets

  2020 ;31(1):120-123. doi: 10.1080/09537104.2019.1609663.
  
  Morici Nuccia, Nava Stefano, Sacco Alice, Viola Giovanna, Oreglia Jacopo, Meani Paolo, Oliva Fabrizio, Ranucci Marco, Leonardi Sergio, Rossini Roberta
  
  Abstract
  
  Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.
  
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• Letter to the editor regarding the results of the retrospective study "Predictors of intra-aortic balloon pump hemodynamic failure in non-acute myocardial infarction cardiogenic shock" published in the American Heart Journal.
  Am Heart J

  2019 07;213():123. doi: S0002-8703(19)30056-0.
  
  Sacco Alice, Morici Nuccia, Oliva Fabrizio
  
  
  
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• Cardiogenic shock: old and new circulatory assist devices: the role of counter-pulsation.
  Eur Heart J Suppl

  2019 Mar;21(Suppl B):B59-B60. doi: 10.1093/eurheartj/suz020.
  
  Viola Giovanna, Morici Nuccia, Sacco Alice, Stucchi Miriam, Brunelli Dario, Cipriani Manlio, Garascia Andrea, Bottiroli Maurizio, Frigerio Maria, Oliva Fabrizio
  
  
  
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• Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome.
  Arterioscler Thromb Vasc Biol

  2019 05;39(5):915-924. doi: 10.1161/ATVBAHA.118.311987.
  
  Ossoli Alice, Simonelli Sara, Varrenti Marisa, Morici Nuccia, Oliva Fabrizio, Stucchi Miriam, Gomaraschi Monica, Strazzella Arianna, Arnaboldi Lorenzo, Thomas Michael J, Sorci-Thomas Mary G, Corsini Alberto, Veglia Fabrizio, Franceschini Guido, Karathanasis Sotirios K, Calabresi Laura
  
  Abstract
  
  Objective- Aim of this study was to evaluate changes in LCAT (lecithin:cholesterol acyltransferase) concentration and activity in patients with an acute coronary syndrome, to investigate if these changes are related to the compromised capacity of HDL (high-density lipoprotein) to promote endothelial nitric oxide (NO) production, and to assess if rhLCAT (recombinant human LCAT) can rescue the defective vasoprotective HDL function. Approach and Results- Thirty ST-segment-elevation myocardial infarction (STEMI) patients were enrolled, and plasma was collected at hospital admission, 48 and 72 hours thereafter, at hospital discharge, and at 30-day follow-up. Plasma LCAT concentration and activity were measured and related to the capacity of HDL to promote NO production in cultured endothelial cells. In vitro studies were performed in which STEMI patients' plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in endothelial cells. The plasma concentration of the LCAT enzyme significantly decreases during STEMI with a parallel significant reduction in LCAT activity. HDL isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with rhLCAT restores HDL ability to promote endothelial NO production, possibly related to significant modification in HDL phospholipid classes. Conclusions- Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during acute coronary syndrome. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in acute coronary syndrome.
  
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• Long-term survival and major outcomes in post-cardiotomy extracorporeal membrane oxygenation for adult patients in cardiogenic shock.
  Ann Cardiothorac Surg

  2019 Jan;8(1):116-122. doi: 10.21037/acs.2018.12.04.
  
  Meani Paolo, Matteucci Matteo, Jiritano Federica, Fina Dario, Panzeri Francesco, Raffa Giuseppe M, Kowalewski Mariusz, Morici Nuccia, Viola Giovanna, Sacco Alice, Oliva Fabrizio, Alyousif Amal, Heuts Sam, Gilbers Martijn, Schreurs Rick, Maessen Jos, Lorusso Roberto
  
  Abstract
  
  Extracorporeal membrane oxygenation (ECMO) in the veno-arterial (VA) configuration is an established method for the treatment of refractory cardiogenic shock. Such a condition characterizes the postoperative course of approximatively 1% of cardiac surgery patients. Although some studies have reported ECMO-related short-term results, little is known about the long-term outcomes of VA-ECMO therapy in the post-cardiotomy setting. Therefore, an extensive literature search was conducted regarding articles published after 1990 reporting postoperative ECMO use. PubMed, EMBASE and Web of Science were searched for sources. In-hospital mortality was high in post-cardiotomy VA-ECMO patients, ranging from 24.8% to 52%. Long-term results were poorly reported. However, based on the limited information available, hospital survivors showed a favorable outcome, with improvement in overall clinical condition, quality of life and limited hospital readmission for cardiac-related events. To conclude, in-hospital outcome in post-cardiotomy ECMO is often unfavorable, post-discharge results show satisfactory condition, with stable improvement of overall patient clinical status and low rate of hospital readmission and cardiac-related adverse events. Data reporting is, however, scarce and hence new and detailed studies are still warranted to investigate such aspects.
  
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• Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel.
  J Am Heart Assoc

  2019 01;8(2):e010956. doi: 10.1161/JAHA.118.010956.
  
  Crimi Gabriele, Morici Nuccia, Ferrario Maurizio, Ferri Luca A, Piatti Luigi, Grosseto Daniele, Cacucci Michele, Mandurino Mirizzi Alessandro, Toso Anna, Piscione Federico, De Carlo Marco, Elia Luigi Raffaele, Trimarco Bruno, Bolognese Leonardo, Bovenzi Francesco M, De Luca Giuseppe, Savonitto Stefano, De Servi Stefano
  
  Abstract
  
  Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( P<0.001) without a difference in ADBRs ( P=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( P<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( P<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.
  
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• Outcomes of Elderly Patients with ST-Elevation or Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
  Am J Med

  2019 02;132(2):209-216. doi: S0002-9343(18)31053-2.
  
  Morici Nuccia, Savonitto Stefano, Ferri Luca A, Grosseto Daniele, Bossi Irene, Sganzerla Paolo, Tortorella Giovanni, Cacucci Michele, Ferrario Maurizio, Crimi Gabriele, Murena Ernesto, Tondi Stefano, Toso Anna, Gandolfo Nicola, Ravera Amelia, Corrada Elena, Mariani Matteo, Di Ascenzo Leonardo, Petronio A Sonia, Cavallini Claudio, Vitrella Giancarlo, Antonicelli Roberto, Piscione Federico, Rogacka Renata, Antolini Laura, Alicandro Gianfranco, La Vecchia Carlo, Piatti Luigi, De Servi Stefano,
  
  Abstract
  
  INTRODUCTION:
  Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far.
  
  METHODS:
  Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke.
  
  RESULTS:
  Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P < .001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7).
  
  CONCLUSIONS:
  Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention.
  
  Copyright © 2018. Published by Elsevier Inc.
  
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• Antithrombotic therapy in ventricular assist device (VAD) management: From ancient beliefs to updated evidence. A narrative review.
  Int J Cardiol Heart Vasc

  2018 Sep;20():20-26. doi: 10.1016/j.ijcha.2018.06.005.
  
  Morici Nuccia, Varrenti Marisa, Brunelli Dario, Perna Enrico, Cipriani Manlio, Ammirati Enrico, Frigerio Maria, Cattaneo Marco, Oliva Fabrizio
  
  Abstract
  
  Platelets play a key role in the pathogenesis of ventricular assist device (VAD) thrombosis; therefore, antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in VAD management. Aspirin is the most used agent and still remains the first-choice drug for lifelong administration after VAD implantation. Anticoagulant drugs are usually recommended, but with a wide range of efficacy targets. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has been used for patients developing a thrombotic event, despite an increased risk of bleeding complications. Although different strategies have been attempted, bleeding and thrombotic events remain frequent and there are no uniform strategies adopted for pharmacological management in the short and mid- or long-term follow up. The aim of this article is to provide an overview of the evidence from randomized clinical trials and observational studies with a focus on the pathophysiologic mechanisms underlying bleeding and thrombosis in VAD patients and the best antithrombotic regimens available.
  
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• Antiplatelet therapy for elderly patients with Acute Coronary Syndromes.
  Aging (Albany NY)

  2018 09;10(9):2220-2221. doi: 10.18632/aging.101553.
  
  Savonitto Stefano, Morici Nuccia, De Servi Stefano
  
  
  
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• Management of cardiogenic shock in acute decompensated chronic heart failure: The ALTSHOCK phase II clinical trial.
  Am Heart J

  2018 10;204():196-201. doi: S0002-8703(18)30217-5.
  
  Morici Nuccia, Oliva Fabrizio, Ajello Silvia, Stucchi Miriam, Sacco Alice, Cipriani Manlio Gianni, De Bonis Michele, Garascia Andrea, Gagliardone Maria Pia, Melisurgo Giulio, Russo Claudio Francesco, La Vecchia Carlo, Frigerio Maria, Pappalardo Federico
  
  Abstract
  
  Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7?days (interquartile range 6-15), and the median dose was 0.08 ?g/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60?days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.
  
  Copyright © 2018 Elsevier Inc. All rights reserved.
  
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• Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?
  Perfusion

  2019 01;34(1):35-41. doi: 10.1177/0267659118787426.
  
  Meani Paolo, Delnoij Thijs, Raffa Giuseppe M, Morici Nuccia, Viola Giovanna, Sacco Alice, Oliva Fabrizio, Heuts Sam, Sels Jan-Willem, Driessen Rob, Roekaerts Paul, Gilbers Martijn, Bidar Elham, Schreurs Rick, Natour Ehsan, Veenstra Leo, Kats Suzanne, Maessen Jos, Lorusso Roberto
  
  Abstract
  
  BACKGROUND:
  Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO.
  
  METHODS:
  Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed.
  
  RESULTS:
  During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge.
  
  CONCLUSION:
  IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.
  
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• In Reply.
  Menopause

  2018 09;25(9):1056-1057. doi: 10.1097/GME.0000000000001156.
  
  Ferri Luca A, Savonitto Stefano, Morici Nuccia
  
  
  
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• Anemia and acute coronary syndrome: current perspectives.
  Vasc Health Risk Manag

  2018 ;14():109-118. doi: 10.2147/VHRM.S140951.
  
  Stucchi Miriam, Cantoni Silvia, Piccinelli Enrico, Savonitto Stefano, Morici Nuccia
  
  Abstract
  
  Reference hemoglobin (Hb) values for the definition of anemia are still largely based on the 1968 WHO Scientific Group report, which established a cutoff value of <13 g/dL for adult men and <12 g/dL for adult nonpregnant women. Subsequent studies identified different normal values according to race and age. Estimated prevalence of anemia on admission in the setting of an acute coronary syndrome (ACS) is between 10% and 43% of the patients depending upon the specific population under investigation. Furthermore, up to 57% of ACS patients may develop hospital-acquired anemia (HAA). Both anemia on admission and HAA are associated with worse short- and long-term mortality, even if different mechanisms contribute to their prognostic impact. Baseline anemia can usually be traced back to preexisting disease that should be specifically investigated and corrected whenever possible. HAA is associated with clinical characteristics, medical therapy and interventional procedures, all eliciting cardiovascular adaptive response that can potentially worsen myocardial ischemia. The intrinsic fragility of anemic patients may limit aggressive medical and interventional therapy due to an increased risk of bleeding, and could independently contribute to worse outcome. However, primary angioplasty for ST elevation ACS should not be delayed because of preexisting (and often not diagnosed) anemia; delaying revascularization to allow fast-track anemia diagnosis is usually feasible and justified in non-ST-elevation ACS. Besides identification and treatment of the underlying causes of anemia, the only readily available means to reverse anemia is red blood cell transfusion. The adequate transfusion threshold is still being debated, although solid evidence suggests reserving red blood cell transfusions for patients with Hb level <8 g/dL and considering it in selected cases with Hb levels of between 8 and 10 g/dL. No evidence supports the use of iron supplements and erythropoiesis-stimulating agents in the setting of ACS.
  
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• Real-world application of currently available decision models for dual antiplatelet therapy duration in acute coronary syndrome.
  J Cardiovasc Med (Hagerstown)

  2018 06;19(6):310-313. doi: 10.2459/JCM.0000000000000655.
  
  Morici Nuccia, Piccinelli Enrico, Brunelli Dario, Sacco Alice, Viola Giovanna, Oreglia Jacopo A, Oliva Fabrizio, Valgimigli Marco
  
  
  
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• Age at menopause, extent of coronary artery disease and outcome among postmenopausal women with acute coronary syndromes.
  Int J Cardiol

  2018 05;259():8-13. doi: S0167-5273(17)37792-6.
  
  Savonitto Stefano, Morici Nuccia, Franco Nicoletta, Misuraca Leonardo, Lenatti Laura, Ferri Luca A, Lo Jacono Emilia, Leuzzi Chiara, Corrada Elena, Aranzulla Tiziana C, Cagnacci Angelo, Colombo Delia, La Vecchia Carlo, Prati Francesco,
  
  Abstract
  
  BACKGROUND:
  Early menopause has been associated with increased cardiovascular mortality, but prospective studies investigating outcomes of postmenopausal women with acute coronary syndromes (ACS) in relation to menopausal age are lacking.
  
  METHODS:
  We analyzed the 1-year outcome of 373 women with acute myocardial infarction enrolled in the Ladies ACS study. All patients underwent coronary angiography, with corelab analysis. Menopause questionnaires were administered during admission. Menopausal age below the median of the study population (50?years) was defined as "early menopause". The composite 1-year outcome included all-cause mortality, recurrent myocardial infarction and stroke.
  
  RESULTS:
  The mean age at index ACS was 73?years (IQR 65-83) for women with early menopause, and 74 (IQR 65-80) for those with late menopause. Patients with early menopause had more prevalent chronic kidney disease (12.8% vs 5.9%, p?=?0.03), whereas there were no differences in all other clinical characteristics, extent of coronary disease at angiography (as assessed by Gensini and SYNTAX scores), as well as interventional treatments. Within 1?year, women with late menopause had significantly better outcome as compared with those with early menopause (6.5% vs 15.3%, p?=?0.007). At logistic regression analysis, late menopause was independently associated with better outcome (OR 0.28; 95% CI 0.12-0.67; p?=?0.004). With each year's delay in the menopause the adjusted risk decreased by 12% (OR 0.88, 0.77-0.99, p?=?0.040).
  
  CONCLUSION:
  Despite comparable clinical and angiographic characteristics, women with late menopausal age experience better outcomes after an ACS as compared with those with early menopause.
  
  Copyright © 2018 Elsevier B.V. All rights reserved.
  
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• Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.
  Circulation

  2018 06;137(23):2435-2445. doi: 10.1161/CIRCULATIONAHA.117.032180.
  
  Savonitto Stefano, Ferri Luca A, Piatti Luigi, Grosseto Daniele, Piovaccari Giancarlo, Morici Nuccia, Bossi Irene, Sganzerla Paolo, Tortorella Giovanni, Cacucci Michele, Ferrario Maurizio, Murena Ernesto, Sibilio Girolamo, Tondi Stefano, Toso Anna, Bongioanni Sergio, Ravera Amelia, Corrada Elena, Mariani Matteo, Di Ascenzo Leonardo, Petronio A Sonia, Cavallini Claudio, Vitrella Giancarlo, Rogacka Renata, Antonicelli Roberto, Cesana Bruno M, De Luca Leonardo, Ottani Filippo, De Luca Giuseppe, Piscione Federico, Moffa Nadia, De Servi Stefano,
  
  Abstract
  
  BACKGROUND:
  Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding.
  
  METHODS:
  In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg.
  
  RESULTS:
  Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; =0.18).
  
  CONCLUSIONS:
  The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial.
  
  CLINICAL TRIAL REGISTRATION:
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.
  
  © 2018 American Heart Association, Inc.
  
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• History of vasomotor symptoms, extent of coronary artery disease, and clinical outcomes after acute coronary syndrome in postmenopausal women.
  Menopause

  2018 06;25(6):635-640. doi: 10.1097/GME.0000000000001064.
  
  Ferri Luca A, Morici Nuccia, Bassanelli Giorgio, Franco Nicoletta, Misuraca Leonardo, Lenatti Laura, Jacono Emilia Lo, Leuzzi Chiara, Corrada Elena, Aranzulla Tiziana C, Colombo Delia, Cagnacci Angelo, Prati Francesco, Savonitto Stefano,
  
  Abstract
  
  OBJECTIVE:
  Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome.
  
  METHODS:
  The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year.
  
  RESULTS:
  Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P?
  CONCLUSIONS:
  In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk factor differences between women with and without a history of VMS.
  
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• Predictors of mortality in hospital survivors with type 2 diabetes mellitus and acute coronary syndromes.
  Diab Vasc Dis Res

  2018 01;15(1):14-23. doi: 10.1177/1479164117735493.
  
  Savonitto Stefano, Morici Nuccia, Nozza Anna, Cosentino Francesco, Perrone Filardi Pasquale, Murena Ernesto, Morocutti Giorgio, Ferri Marco, Cavallini Claudio, Eijkemans Marinus Jc, Stähli Barbara E, Schrieks Ilse C, Toyama Tadashi, Lambers Heerspink H J, Malmberg Klas, Schwartz Gregory G, Lincoff A Michael, Ryden Lars, Tardif Jean Claude, Grobbee Diederick E
  
  Abstract
  
  AIM:
  To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome.
  
  METHODS AND RESULTS:
  A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2?years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio?=?1.68; 95% confidence interval?=?1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio?=?2.28; 95% confidence interval?=?1.77-2.93; 18% of prediction), age (hazard ratio?=?1.04; 95% confidence interval?=?1.02-1.05; 15% of prediction), heart rate (hazard ratio?=?1.02; 95% confidence interval?=?1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio?=?1.11; 95% confidence interval?=?1.03-1.19; 8% of prediction), haemoglobin (hazard ratio?=?1.01; 95% confidence interval?=?1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio?=?1.61; 95% confidence interval?=?1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio?=?1.40; 95% confidence interval?=?1.05-1.87; 6% of prediction).
  
  CONCLUSION:
  In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.
  
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• von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.
  Thromb Res

  2017 Jul;155():78-85. doi: S0049-3848(17)30326-2.
  
  Morici Nuccia, Cantoni Silvia, Panzeri Francesco, Sacco Alice, Rusconi Chiara, Stucchi Miriam, Oliva Fabrizio, Cattaneo Marco
  
  Abstract
  
  BACKGROUND:
  Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS.
  
  METHODS AND RESULTS:
  Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS.
  
  CONCLUSIONS:
  The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist.
  
  Copyright © 2017 Elsevier Ltd. All rights reserved.
  
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• Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.
  Am J Med

  2017 09;130(9):1068-1075. doi: S0002-9343(17)30258-9.
  
  Morici Nuccia, Savonitto Stefano, Ponticelli Claudio, Schrieks Ilse C, Nozza Anna, Cosentino Francesco, Stähli Barbara E, Perrone Filardi Pasquale, Schwartz Gregory G, Mellbin Linda, Lincoff A Michael, Tardif Jean-Claude, Grobbee Diederick E
  
  Abstract
  
  BACKGROUND:
  Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting.
  
  METHODS:
  We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure.
  
  RESULTS:
  Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001).
  
  CONCLUSIONS:
  Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Antiplatelet and Anticoagulation Treatment in Patients with Thrombocytopenia.
  Curr Pharm Des

  2017 ;23(9):1354-1365. doi: 10.2174/1381612822666161205113119.
  
  Morici Nuccia, Cantoni Silvia, Vallerio Paola, Cattaneo Marco, Savonitto Stefano
  
  Abstract
  
  Thrombocytopenia (TP) is a common finding in patients hospitalized for cardiovascular causes and needing antiplatelet and anticoagulant therapies. However, TP is not only a numeric parameter, but mostly a dynamic condition affected by the patients' underlying disorders and concomitant treatments. Platelets are important players in the hemostatic process, taking part to both primary and secondary hemostasis. Although both TP and antithrombotic treatment contribute to the risk of bleeding, the complexity of the pathogenesis of bleeding events makes it difficult to predict them accurately simply based on these two parameters. It should be considered that, under certain clinical conditions, TP may be associated with an increased risk of thrombosis. In order to manage antithrombotic therapies in patients with TP, the frail balance between bleeding and thrombotic complications needs to be estimated. A joint hematological and cardiological evaluation is mandatory in order to avoid stopping an otherwise lifesaving treatment and to decrease the individual patient risk for both thrombotic and/or bleeding events, in each different setting. The purpose of this review is to describe an operative work flow aimed at helping clinicians to face this challenging issue.
  
  Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
  
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• A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization: Design and rationale of the randomized Elderly-ACS 2 study.
  Am Heart J

  2016 Nov;181():101-106. doi: S0002-8703(16)30171-5.
  
  Ferri Luca A, Morici Nuccia, Grosseto Daniele, Tortorella Giovanni, Bossi Irene, Sganzerla Paolo, Cacucci Michele, Sibilio Girolamo, Tondi Stefano, Toso Anna, Ferrario Maurizio, Gandolfo Nicola, Ravera Amelia, Mariani Matteo, Corrada Elena, Di Ascenzo Leonardo, Petronio Anna Sonia, Cavallini Claudio, Moffa Nadia, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  BACKGROUND:
  Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding.
  
  STUDY DESIGN:
  The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score).
  
  CONCLUSION:
  The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).
  
  Copyright © 2016 Elsevier Inc. All rights reserved.
  
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• Age at Menopause and Extent of Coronary Artery Disease Among Postmenopausal Women with Acute Coronary Syndromes.
  Am J Med

  2016 Nov;129(11):1205-1212. doi: S0002-9343(16)30564-2.
  
  Savonitto Stefano, Colombo Delia, Franco Nicoletta, Misuraca Leonardo, Lenatti Laura, Romano Ilaria J, Morici Nuccia, Lo Jacono Emilia, Leuzzi Chiara, Corrada Elena, Aranzulla Tiziana C, Petronio A Sonia, Bellia Gilberto, Romagnoli Enrico, Cagnacci Angelo, Zoccai Giuseppe Biondi, Prati Francesco,
  
  Abstract
  
  BACKGROUND:
  Epidemiological studies have shown a higher risk of cardiovascular mortality associated with early menopause, but the relation between menopausal age and extent of coronary artery disease after menopause is unknown. We assessed the relation between menopausal age and extent of coronary disease in postmenopausal women with an acute coronary syndrome.
  
  METHODS:
  A prospective study was conducted in patients ?55 years old undergoing coronary angiography for an acute coronary syndrome. Enrollment was stratified by sex (women/men ratio 2:1) and age (55-64, 65-74, 75-85, and >85 years). Women were administered menopause questionnaires during admission. An independent core lab quantified coronary artery disease extent using the Gensini Score, which classifies both significant (>50%) and nonsignificant lesions. Linear correlation was used to appraise the association between the Gensini score and menopausal age.
  
  RESULTS:
  We enrolled 675 patients, 249 men and 426 women (mean age 74 years). The mean Gensini score was 60 ± 36 in men vs 50 ± 32 in women (P <.001), being higher among men at any age. The median menopausal age of women was 50 years. Risk factors and age at first acute coronary syndrome were identical among women below and above the median menopausal age. The Gensini score in women showed a weak association with age (R = 0.127; P = .0129), but not with menopausal age (R = 0.063; P = .228). At multivariable analysis, ejection fraction, female sex, and ST elevation myocardial infarction were independent predictors of the Gensini score in the overall population.
  
  CONCLUSIONS:
  Menopausal age was not associated with the extent of coronary artery disease. Age at first acute coronary syndrome presentation, risk factors, and prior cardiovascular events were not affected by menopausal age. (The LADIES ACS study: NCT01997307).
  
  Copyright © 2016 Elsevier Inc. All rights reserved.
  
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• Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
  Open Heart

  ;3(2):e000472.
  
  Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
  
  Abstract
  
  OBJECTIVE:
  To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
  
  METHODS:
  We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
  
  RESULTS:
  Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7?ng/mL (sensitivity 46%, specificity 84%).
  
  CONCLUSIONS:
  In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
  
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• Invasive Management for Elderly Adults with Acute Coronary Syndrome: Where Are We Now?
  J Am Geriatr Soc

  2016 11;64(11):2396-2397. doi: 10.1111/jgs.14466.
  
  Morici Nuccia, Savonitto Stefano, Biondi-Zoccai Giuseppe, De Servi Stefano
  
  
  
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• Vasopressors and inotropes in cardiogenic shock: is there room for "adrenaline resuscitation"?
  Crit Care

  2016 Sep;20(1):302.
  
  Morici Nuccia, Stucchi Miriam, Sacco Alice, Bottiroli Maurizio A, Oliva Fabrizio,
  
  
  
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• Ticagrelor for left ventricular assist device thrombosis: A new therapeutic option to be evaluated with caution.
  Int J Cardiol

  2016 Oct;221():58-9. doi: 10.1016/j.ijcard.2016.06.304.
  
  Morici Nuccia, Perna Enrico, Cipriani Manlio, Femia Eti Alessandra, Oliva Fabrizio, Frigerio Maria, Cattaneo Marco
  
  
  
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• Allogeneic peripheral blood stem cell transplantation and accelerated atherosclerosis: An intriguing association needing targeted surveillance. Lessons from a rare case of acute anterior myocardial infarction.
  Eur Heart J Acute Cardiovasc Care

  2020 Oct;9(7):NP3-NP7. doi: 10.1177/2048872616652311.
  
  Scudiero Laura, Soriano Francesco, Morici Nuccia, Grillo Giovanni, Belli Oriana, Sacco Alice, Cipriani Manlio, Pedrotti Patrizia, Quattrocchi Giuseppina, Klugmann Silvio, Oliva Fabrizio
  
  Abstract
  
  We report the case of a 23-year-old man who developed an acute ST-elevation myocardial infarction secondary to acute thrombotic occlusion of the proximal left anterior descending coronary artery five years after undergoing chemotherapy, radiotherapy, haematopoietic stem cell transplantation for acute lymphoblastic leukaemia and bulky mediastinal mass involving the pleura and pericardium. His medical history also included Graft versus Host Disease developed 13 months after transplantation and acute myocarditis three months before the actual hospital admission. To the best of our knowledge, coronary artery disease as a complication of haematopoietic stem cell transplantation and low-dose mediastinal radiation therapy in young patients has been rarely reported in the medical literature. Clinicians should have a high degree of suspicion of coronary artery disease in patients treated with allogeneic haematopoietic stem cell transplantation, especially in patients previously treated with target mediastinal radiotherapy, as a group at risk of premature and significantly accelerated atherosclerosis, in order to make a timely and correct diagnosis.
  
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• Bridge therapy or standard treatment for urgent surgery after coronary stent implantation: Analysis of 314 patients.
  Vascul Pharmacol

  2016 May;80():85-90. doi: 10.1016/j.vph.2015.11.085.
  
  De Servi Stefano, Morici Nuccia, Boschetti Enrico, Rossini Roberta, Martina Paola, Musumeci Giuseppe, D'Urbano Maurizio, Lazzari Ludovico, La Vecchia Carlo, Senni Michele, Klugmann Silvio, Savonitto Stefano
  
  Abstract
  
  Intravenous administration of a short acting glycoprotein IIb/IIIa inhibitor has been proposed as a bridge to surgery in patients on dual antiplatelet treatment, but data in comparison with other treatment options are not available. We conducted a retrospective analysis of consecutive patients who underwent un-deferrable, non-emergency surgery after coronary stenting. The bridge therapy was performed after discontinuation of the oral P2Y12 inhibitor by using i.v. tirofiban infusion. Net Adverse Clinical Events (NACE) was the primary outcome. We analyzed 314 consecutive patients: the bridge strategy was performed in 87 patients, whereas 227 were treated with other treatment options and represent the control group. Thirty-day NACE occurred in 8% of patients in the bridge group and in 22.5% in the control group (p < 0.01). Bridge therapy was associated with decreased 30-day NACE rate [Odds ratio (OR) 0.30; 95% confidence interval (CI) 0.13-0.39; p < 0.01], particularly when the time interval between stenting and surgery was ? 60 days (OR 0.09, 95% CI 0.01-0.72; p = 0.02). There were no cases of stent thrombosis in the bridge group and 3 (1.3%) in the control group. Bridge therapy was associated with decreased events rates as compared to both patients with and without P2Y12 inhibitors discontinuation in the control group. After adjustment for the most relevant covariates, the favorable effect of the bridge therapy was not materially modified. In conclusion, perioperative bridge therapy using tirofiban was associated with reduced 30-day NACE rate, particularly when surgery was performed within 60 days after stent implantation.
  
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• [A novel standard protocol of long-term follow-up shared with general practitioners after percutaneous coronary intervention: appropriateness and economic impact].
  G Ital Cardiol (Rome)

  2015 Oct;16(10):565-73. doi: 10.1714/2028.22042.
  
  Lettieri Corrado, Colombo Paola, Rosiello Renato, Morici Nuccia, Parogni Pierpaolo, Musumeci Giuseppe, Tabaglio Erminio, Zadra Alessandro, Cattaneo Maria Grazia, Soriano Francesco, Galavotti Maurizio, Klugmann Silvio, Senni Michele, Valsecchi Orazio, Zanini Roberto, Rossini Roberta
  
  Abstract
  
  BACKGROUND:
  Follow-up modalities for patients undergoing percutaneous coronary intervention (PCI) are not well defined and standard protocols have been not established. The purpose of this study was to assess: a) the frequency and patterns of cardiology visits, echocardiographic examinations and stress tests after PCI in clinical practice; b) the impact of a multidisciplinary protocol of long-term follow-up after PCI shared with general practitioners on the appropriateness and reduction in healthcare costs.
  
  METHODS:
  A total of 780 patients who underwent PCI in 2010 in two Italian hospitals were analyzed. The number of cardiological examinations (total, routine and clinically driven) performed during 2 years of follow-up were recorded and stratified according to the patient's risk profile. The latter was defined according to the multidisciplinary protocol. In addition, a simulation of the spread between provided and necessary tests (according to the multidisciplinary protocol) was carried out.
  
  RESULTS:
  The mean number of cardiological examinations per patient provided during follow-up was 5, of which 4.4 were routine tests in asymptomatic patients. Routine tests were performed more frequently in patients at low risk compared to those at higher risk. By applying the multidisciplinary protocol to the case mix and by merging clinical visit and stress test or echocardiographic examination, a reduction of 0.87 tests per patient/year would be expected. This reduction would result in a 39% decrease in follow-up examinations in this specific clinical setting.
  
  CONCLUSIONS:
  This observational study demonstrates that unnecessary cardiological clinical and functional tests are often performed in long-term follow-up of patients submitted to PCI. The application of a standard protocol of follow-up shared with general practitioners may help avoiding unnecessary consultations, thus reducing healthcare costs.
  
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• [Treatment of acute coronary syndrome in older adults and high-risk patients."When the going gets tough?"].
  Recenti Prog Med

  2015 Oct;106(10):495-506. doi: 10.1701/2032.22082.
  
  Bassanelli Giorgio, Morici Nuccia, De Luca Leonardo, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  The increasing life expectancy in older adults and the better survival of patients with multiple pathologies require the capability to treat complex clinical conditions with an increased risk of iatrogenic complications. Nevertheless, recent improvements in the pharmacological and interventional treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic nihilism to a more active management of complex ACS cases. Despite the paucity of specific randomized clinical trials, observational studies seem to show benefit of an early invasive treatment in these patients. This approach requires close cooperation of clinical intensivists, interventional cardiologists and cardiovascular surgeons either in a specialized heart center or in a network of hospitals.
  
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• [The conundrum of therapeutic management in acute myocardial infarction complicated by endoventricular thrombosis: moving between different risks].
  G Ital Cardiol (Rome)

  ;16(7-8):437-41. doi: 10.1714/1954.21248.
  
  Varrenti Marisa, Morici Nuccia, De Chiara Benedetta, Oreglia Jacopo Andrea, Pedrotti Patrizia, Giannattasio Cristina, Klugmann Silvio, Roghi Alberto
  
  Abstract
  
  Coronary artery disease is a rare entity in young patients and accurate assessment of its prevalence is difficult. Although coronary artery disease is frequently a silent process, it may also acutely present with myocardial infarction (MI). One of the most feared complications of MI is left ventricular thrombus formation. Transthoracic echocardiography is recommended for all patients with MI, and cardiac magnetic resonance should be considered because of its higher sensitivity if thrombus cannot clearly be demonstrated. The optimal treatment is based on anticoagulant therapy that should be started early and maintained for 3-4 months after the index event. We report the case of a 35-year-old male patient with anterior MI, complicated by left ventricular thrombus formation, extensive edema, microvascular obstruction and hemorrhagic core of the apical septum on cardiac magnetic resonance assessment.
  
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• Epicardial adipose tissue thickness and acute coronary syndrome: a matter of how much or how?
  Int J Cardiol

  2015 Nov;199():8-9. doi: 10.1016/j.ijcard.2015.06.168.
  
  Aprigliano Gianfranco, Scuteri Lea, Iafelice Ida, Li Volsi Laura, Cuko Besart, Palloshi Altin, Pisani Matteo, Bonizzato Sara, Bianchi Michele, Morici Nuccia
  
  
  
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• Antithrombotic therapy before, during and after emergency angioplasty for ST elevation myocardial infarction.
  Eur Heart J Acute Cardiovasc Care

  2017 Mar;6(2):173-190. doi: 10.1177/2048872615590148.
  
  Savonitto Stefano, De Luca Giuseppe, Goldstein Patrick, van T' Hof Arnoud, Zeymer Uwe, Morici Nuccia, Thiele Holger, Montalescot Gilles, Bolognese Leonardo
  
  Abstract
  
  The first three hours after symptom onset hold the maximum potential for myocardial reperfusion and salvage in ST-elevation myocardial infarction (STEMI) patients. During this period timely primary percutaneous coronary intervention (PPCI) or, when PPCI is not promptly feasible, pre-hospital administration of fibrinolyis or a glycoprotein IIb/IIIa-inhibitor (GPI) have been shown to restore coronary patency and reperfusion and even result in myocardial infarction (MI) abortion. On the other hand, oral antiplatelet therapy may not yet guarantee sufficient platelet inhibition. Patients presenting after this golden time have less, if any, benefit from an aggressive antithrombotic treatment prior to PPCI. Antithrombotic treatment during primary angioplasty should be tailored on the basis of the coronary thrombotic burden, vascular approach and the patient's risk of bleeding complications. A GPI-based approach may be favourable in patients presenting early with large MI and high thrombus burden, whereas a bivalirudin-based approach without GPI may be preferred in patients with higher bleeding risk. There are no data to support the use of GPI in bailout conditions. The powerful oral P2Y inhibitors, prasugrel and ticagrelor, have been clearly shown to prevent stent thrombosis and recurrent ischaemic events after emergency percutaneous coronary intervention in STEMI patients. Open issues remaining are the treatment of patients with high bleeding risk, such as the elderly and those requiring anticoagulation, as well as the duration of dual antiplatelet therapy after STEMI.
  
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• Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2 years.
  Clin Mol Allergy

  2015 ;13(1):14. doi: 10.1186/s12948-015-0013-0.
  
  Pastorello Elide Anna, Farioli Laura, Losappio Laura Michelina, Morici Nuccia, Di Biase Matteo, Nichelatti Michele, Schroeder Jan Walter, Balossi Luca, Klugmann Silvio
  
  Abstract
  
  BACKGROUND:
  One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients.
  
  METHODS:
  We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE). The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed.
  
  RESULTS:
  The ACS population was divided in two groups: patients with MACE (n?=?23) and patients without MACE (n?=?42). The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p?=?0.0001, p?
  CONCLUSION:
  In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.
  
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• Sex-Related Outcomes in Elderly Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome: Insights From the Italian Elderly ACS Study.
  JACC Cardiovasc Interv

  2015 May;8(6):791-796. doi: S1936-8798(15)00259-9.
  
  De Carlo Marco, Morici Nuccia, Savonitto Stefano, Grassia Vincenzo, Sbarzaglia Paolo, Tamburrini Paola, Cavallini Claudio, Galvani Marcello, Ortolani Paolo, De Servi Stefano, Petronio A Sonia
  
  Abstract
  
  OBJECTIVES:
  This study sought to investigate sex-related differences in treatment and outcomes in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS).
  
  BACKGROUND:
  Female sex and older age are usually associated with worse outcome in NSTEACS. The Italian Elderly ACS study enrolled NSTEACS patients aged 75 years of age and older in a randomized trial comparing an early aggressive with an initially conservative strategy and in a registry of patients with ?1 exclusion criteria of the trial.
  
  METHODS:
  We compared sexes in the pooled populations of the trial and registry.
  
  RESULTS:
  A total of 645 patients (313 from the trial and 332 from the registry), including 301 women (47%), were enrolled. Women were slightly older than men (82.1 ± 5.0 years vs. 81.2 ± 4.5 years; p = 0.02), had lower hemoglobin levels (12.5 ± 1.6 g/dl vs. 13.3 ± 1.9 g/dl; p < 0.001), and underwent fewer coronary revascularizations during the index admission (37.2% vs. 45.0%; p = 0.04). In-hospital adverse event rates were similar in both sexes; severe bleeding was uncommon (0.3% vs. 0%). The 1-year primary endpoint (composite of death, nonfatal myocardial infarction, disabling stroke, cardiac rehospitalization, and severe bleeding) occurred less often in women (27.6% vs. 38.7%; p < 0.01). Women not undergoing revascularization showed a 3-fold higher mortality, both in-hospital (8.5% vs. 2.7%; p = 0.05) and at 1 year (21.6% vs. 8.1%; p = 0.002).
  
  CONCLUSIONS:
  Elderly women had a similar in-hospital outcome and better 1-year outcome compared with men. Coronary revascularization in women was associated with lower 1-year mortality, without an increase in severe bleeding. Elderly women with NSTEACS should always be considered for early revascularization.
  
  Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• A risk score for predicting 1-year mortality in patients ?75 years of age presenting with non-ST-elevation acute coronary syndrome.
  Am J Cardiol

  2015 Jul;116(2):208-13. doi: 10.1016/j.amjcard.2015.04.015.
  
  Angeli Fabio, Cavallini Claudio, Verdecchia Paolo, Morici Nuccia, Del Pinto Maurizio, Petronio Anna Sonia, Antonicelli Roberto, Murena Ernesto, Bossi Irene, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  Approximately 1/3 of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) are ?75 years of age. Risk stratification in these patients is generally difficult because supporting evidence is scarce. The investigators developed and validated a simple risk prediction score for 1-year mortality in patients ?75 years of age presenting with NSTE ACS. The derivation cohort was the Italian Elderly ACS trial, which included 313 patients with NSTE ACS aged ?75 years. A logistic regression model was developed to predict 1-year mortality. The validation cohort was a registry cohort of 332 patients with NSTE ACS meeting the same inclusion criteria as for the Italian Elderly ACS trial but excluded from the trial for any reason. The risk score included 5 statistically significant covariates: previous vascular event, hemoglobin level, estimated glomerular filtration rate, ischemic electrocardiographic changes, and elevated troponin level. The model allowed a maximum score of 6. The score demonstrated a good discriminating power (C statistic = 0.739) and calibration, even among subgroups defined by gender and age. When validated in the registry cohort, the scoring system confirmed a strong association with the risk for all-cause death. Moreover, a score ?3 (the highest baseline risk group) identified a subset of patients with NSTE ACS most likely to benefit from an invasive approach. In conclusion, the risk for 1-year mortality in patients ?75 years of age with NSTE ACS is substantial and can be predicted through a score that can be easily derived at the bedside at hospital presentation. The score may help in guiding treatment strategy.
  
  Copyright © 2015 Elsevier Inc. All rights reserved.
  
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• Management and Long-Term Prognosis of Spontaneous Coronary Artery Dissection.
  Am J Cardiol

  2015 Jul;116(1):66-73. doi: 10.1016/j.amjcard.2015.03.039.
  
  Lettieri Corrado, Zavalloni Dennis, Rossini Roberta, Morici Nuccia, Ettori Federica, Leonzi Ornella, Latib Azeem, Ferlini Marco, Trabattoni Daniela, Colombo Paola, Galli Mario, Tarantini Giuseppe, Napodano Massimo, Piccaluga Emanuela, Passamonti Enrico, Sganzerla Paolo, Ielasi Alfonso, Coccato Micol, Martinoni Alessandro, Musumeci Giuseppe, Zanini Roberto, Castiglioni Battistina
  
  Abstract
  
  The optimal management and short- and long-term prognoses of spontaneous coronary artery dissection (SCAD) remain not well defined. The aim of this observational multicenter study was to assess long-term clinical outcomes in patients with SCAD. In-hospital and long-term outcomes were assessed in 134 patients with documented SCAD, as well as the clinical impact and predictors of a conservative rather than a revascularization strategy of treatment. The mean age was 52 ± 11, years and 81% of patients were female. SCAD presented as an acute coronary syndromes in 93% of patients. A conservative strategy was performed in 58% of patients and revascularization in 42%. On multivariate analysis, distal versus proximal or mid location of dissection (odds ratio 9.27) and basal Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 versus 0 or 1 (odds ratio 0.20) were independent predictors of conservative versus revascularization strategy. A conservative strategy was associated with better in-hospital outcomes compared with revascularization (rates of major adverse cardiac events 3.8% and 16.1%, respectively, p = 0.028); however, no significant differences were observed in the long-term outcomes. In conclusion, in this large observational study of patients with SCAD, angiographic features significantly influenced the treatment strategy, providing an excellent short- and long-term prognosis.
  
  Copyright © 2015 Elsevier Inc. All rights reserved.
  
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• Cardiogenic shock: How to overcome a clinical dilemma. Unmet needs in Emergency medicine.
  Int J Cardiol

  2015 ;186():19-21. doi: 10.1016/j.ijcard.2015.02.111.
  
  Morici Nuccia, Sacco Alice, Paino Roberto, Oreglia Jacopo Andrea, Bottiroli Maurizio, Senni Michele, Nichelatti Michele, Canova Paolo, Russo Claudio, Garascia Andrea, Kulgmann Silvio, Frigerio Maria, Oliva Fabrizio
  
  
  
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• Effect of an invasive strategy on outcome in patients ?75 years of age with non-ST-elevation acute coronary syndrome.
  Am J Cardiol

  2015 Mar;115(5):576-80. doi: 10.1016/j.amjcard.2014.12.005.
  
  Galasso Gennaro, De Servi Stefano, Savonitto Stefano, Strisciuglio Teresa, Piccolo Raffaele, Morici Nuccia, Murena Ernesto, Cavallini Claudio, Petronio Anna Sonia, Piscione Federico
  
  Abstract
  
  The Italian Elderly ACS study was the first randomized controlled trial comparing an early aggressive with an initially conservative strategy in patients with non-ST-segment elevation acute coronary syndromes aged ?75 years, with the results showing no significant benefit of early aggressive therapy. The aim of this study was to evaluate the outcomes of trial patients, according to the treatment actually received during hospitalization. The trial enrolled 313 patients. The primary end point was the composite of death, myocardial infarction (MI), disabling stroke, and repeat hospital stay for cardiovascular causes or bleeding within 1 year. All patients in whom coronary angiography was performed during initial hospitalization were defined as having undergone invasive treatment (182 patients), whereas all patients who did not undergo coronary angiography were classified as medically managed (conservative treatment [CT] group, 131 patients). The primary end point occurred in 53 patients (40.5%) in the CT group and 45 patients (24.7%) in the invasive treatment group (hazard ratio 0.56, 95% confidence interval 0.37 to 0.83, p = 0.003). The invasive treatment group showed significantly lower rates of MI (6% vs 13% in the CT group; hazard ratio 0.43, 95% confidence interval 0.20 to 0.92, p = 0.034) and the aggregate of death and MI (14.3% vs 27.5% CT group; hazard ratio 0.48, 95% confidence interval 0.29 to 0.81, p = 0.004). In conclusion, elderly patients with non-ST-segment elevation acute coronary syndromes treated invasively experienced significantly better survival free from the composite of all-cause mortality, nonfatal MI, disabling stroke, and repeat hospitalization for cardiovascular causes or bleeding.
  
  Copyright © 2015 Elsevier Inc. All rights reserved.
  
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• Acute Kidney Injury in Elderly Patients With Non-ST Elevation Acute Coronary Syndrome: Insights From the Italian Elderly: ACS Study.
  Angiology

  2015 Oct;66(9):826-30. doi: 10.1177/0003319714567738.
  
  Toso Anna, Servi Stefano De, Leoncini Mario, Morici Nuccia, Murena Ernesto, Antonicelli Roberto, Cavallini Claudio, Petronio Anna Sonia, Steffenino Giuseppe, Piscione Federico, Bellandi Francesco, Savonitto Stefano
  
  Abstract
  
  We examined the incidence and predictors of acute kidney injury (AKI) in elderly patients (?75 years) enrolled in the prospective Italian Elderly acute coronary syndrome (ACS) study and explored the impact of AKI on clinical outcome. Acute kidney injury, defined according to the Acute Kidney Injury Network criteria, occurred in 128 (21%) of 615 patients. Patients submitted to coronary angiographic procedures did not present higher rate of AKI. The only baseline variables independently associated with AKI development were creatinine clearance (odds ratio [OR]: 0.98; 95% confidence interval [CI]: 0.97-0.99) and left ventricular ejection fraction (OR: 0.98; 95% CI: 0.96-0.99). Adverse clinical events were significantly higher in patients who developed AKI. After multivariable adjustment, AKI (hazard ratio: 2.73; 95% CI: 1.87-4.0) was an independent predictor of all-cause mortality within 1 year.
  
  © The Author(s) 2015.
  
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• Right anterior mini-thoracotomy direct aortic self-expanding trans-catheter aortic valve implantation: A single center experience.
  Int J Cardiol

  2015 Feb;181():437-42. doi: 10.1016/j.ijcard.2014.11.108.
  
  Bruschi Giuseppe, De Marco Federico, Botta Luca, Barosi Alberto, Colombo Paola, Mauri Silvia, Cannata Aldo, Morici Nuccia, Colombo Tiziano, Fratto Pasquale, Nonini Sandra, Soriano Francesco, Mondino Michele, Giannattasio Cristina, Klugmann Silvio
  
  Abstract
  
  OBJECTIVE:
  Transcatheter aortic valve implantation (TAVI) has been designed to treat elderly patients with severe aortic stenosis at high risk for surgery. These patients are also often affected by severe iliac-femoral arteriopathy, rendering the trans-femoral approach unusable. We report our experience with the direct-aortic approach to treat these patients.
  
  METHODS:
  From May 2008 to November 2013 two hundred and thirty-two patients (131 female, 56%) with severe symptomatic aortic stenosis and no reasonable surgical option due to excessive risk were evaluated for TAVI at our department. Of these patients, 202 were deemed eligible for TAVI. Of this group, 50 underwent CoreValve implantation by the direct aortic approach through a right anterior mini-thoracotmy (28 female, 56%), mean age 81.2±6.9. A combined team of cardiologists, cardiac surgeons with expertise in hybrid procedures, and anesthetists performed all the procedures.
  
  RESULTS:
  Twenty-eight (56%) patients were female and 11 (22%) were redo at TAVI. We used a 23-mm CoreValve Evolute in 3 patients (6%), and the most used valve size was the 29mm in 46% of patients. Mean hemodynamic trans-aortic gradient was less than 5mmHg. The paravalvular regurgitation was ? grade 1 in 46 patients as assessed by peri-procedural transesophageal echocardiography (TEE). Seven patients (7/43, 16%) required a permanent pacemaker implantation; 30-day mortality was 6% (3 patients). Seven patients (14.8%) died during follow-up. Actuarial survival at 2years is 84.7±5.3%.
  
  CONCLUSIONS:
  Transcatheter aortic valve implantation with the direct aortic approach is safe and feasible, offering a new attractive option to treat selected high-risk patients with severe aortic stenosis and peripheral vasculopathy, including those requiring a re-do procedure.
  
  Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
  
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• Renal dysfunction, coronary revascularization and mortality among elderly patients with non ST elevation acute coronary syndrome.
  Eur Heart J Acute Cardiovasc Care

  2015 Oct;4(5):453-60. doi: 10.1177/2048872614557221.
  
  Morici Nuccia, De Servi Stefano, Toso Anna, Murena Ernesto, Piscione Federico, Bolognese Leonardo, Petronio Anna Sonia, Antonicelli Roberto, Cavallini Claudio, Angeli Fabio, Savonitto Stefano
  
  Abstract
  
  AIMS:
  To determine the association between baseline creatinine clearance (CrCl), coronary revascularization during index admission, and 1-year mortality in elderly patients with an acute coronary syndrome (ACS).
  
  METHODS AND RESULTS:
  We estimated CrCl using the Cockcroft-Gault (CG) formula in 313 patients aged ? 75 years enrolled in a prospective study of treatment strategies in non ST-elevation ACS (NSTEACS). Patients were stratified into four groups according to CrCl on admission (using a cutoff of 45 ml/min) and coronary revascularization versus medical management. The mean age of the study population was 81 years and the median serum creatinine level on admission was 1.0 mg/dl (interquartile range (IQR) 0.8-1.3). Patients with impaired renal function treated medically had higher in-hospital and 1-year mortality, especially if compared with patients with preserved renal function undergoing revascularization (1-year mortality 22.9% versus 4.9%). Across the spectrum of CrCl categories, coronary revascularization was independently associated with a lower risk of mortality (HR 0.405; 95% CI 0.174-0.940; p=0.035).
  
  CONCLUSIONS:
  In elderly patients with NSTEACS, coronary revascularization decreases the risk of 1-year death across each CrCl category, and is one of the most powerful predictors of 1-year outcome.
  
  © The European Society of Cardiology 2014.
  
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• Anemia in octogenarians with non-ST elevation acute coronary syndrome: aging or disease?
  Int J Cardiol

  2014 Oct;176(3):1147-9. doi: 10.1016/j.ijcard.2014.07.283.
  
  Morici Nuccia, Cantoni Silvia, Antonicelli Roberto, Murena Ernesto, Cavallini Claudio, Petronio Anna Sonia, Toso Anna, Bonechi Francesco, De Servi Stefano, Savonitto Stefano
  
  
  
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• Mortality in the PARTNER trials: transfemoral is better.
  J Am Coll Cardiol

  2014 Jul;64(2):169-71. doi: 10.1016/j.jacc.2014.04.034.
  
  Bruschi Giuseppe, Morici Nuccia
  
  
  
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• Update: acute coronary syndromes (VI): treatment of acute coronary syndromes in the elderly and in patients with comorbidities.
  Rev Esp Cardiol (Engl Ed)

  2014 Jul;67(7):564-73. doi: 10.1016/j.rec.2014.02.008.
  
  Savonitto Stefano, Morici Nuccia, De Servi Stefano
  
  Abstract
  
  Acute coronary syndromes have a wide spectrum of clinical presentations and risk of adverse outcomes. A distinction should be made between treatable (extent of ischemia, severity of coronary disease and acute hemodynamic deterioration) and untreatable risk (advanced age, prior myocardial damage, chronic kidney dysfunction, other comorbidities). Most of the patients with "untreatable" risk have been excluded from the "guideline-generating" clinical trials. In recent years, despite the paucity of specific randomized trials, major advances have been completed in the management of elderly patients and patients with comorbidities: from therapeutic nihilism to careful titration of antithrombotic agents, a shift toward the radial approach to percutaneous coronary interventions, and also to less-invasive cardiac surgery. Further advances should be expected from the development of drug regimens suitable for use in the elderly and in patients with renal dysfunction, from a systematic multidisciplinary approach to the management of patents with diabetes mellitus and anemia, and from the courage to undertake randomized trials involving these high-risk populations.
  
  Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.
  
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• Serum tryptase: a new biomarker in patients with acute coronary syndrome?
  Int Arch Allergy Immunol

  2014 ;164(2):97-105. doi: 10.1159/000360164.
  
  Pastorello Elide Anna, Morici Nuccia, Farioli Laura, Di Biase Matteo, Losappio Laura Michelina, Nichelatti Michele, Lupica Loredana, Schroeder Jan Walter, Stafylaraki Chrysi, Klugmann Silvio
  
  Abstract
  
  BACKGROUND:
  Mast cell tryptase has recently been reported to be involved in atherosclerotic plaque destabilization. However, the results of these reports are conflicting.
  
  METHODS:
  The aim of this study was to characterize the role of tryptase as a prognostic marker of patient cardiovascular complexity in acute coronary syndrome (ACS). Furthermore, its association with an angiographic scoring system [defined by the SYNergy between percutaneous coronary intervention (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score] was examined. The serum tryptase was measured at admission in 65 consecutive ACS patients and in 35 healthy controls. In the patients with ACS, a composite measure of clinical and angiographic patient cardiovascular complexity was indicated by two of the following: clinical adverse events at hospitalization, at least 2 epicardial coronary arteries involved in the atherosclerotic disease, more than 1 stent implanted or more than 2 coronary artery disease risk factors.
  
  RESULTS:
  The tryptase measurements were lower in patients without the composite measure (p < 0.0005). Linear regression showed a significant relationship between tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity troponin values did not correlate with either the composite outcome or the SX-score. The predictive accuracy of serum tryptase for the composite outcome was set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%).
  
  CONCLUSION:
  In ACS patients, serum tryptase levels at admission may predict patient cardiovascular complexity more reliably than currently known biomarkers. Further studies are needed to demonstrate the long-term prognostic role of this biomarker in ACS.
  
  © 2014 S. Karger AG, Basel.
  
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• One-year mortality in elderly adults with non-ST-elevation acute coronary syndrome: effect of diabetic status and admission hyperglycemia.
  J Am Geriatr Soc

  2014 Jul;62(7):1297-303. doi: 10.1111/jgs.12900.
  
  Savonitto Stefano, Morici Nuccia, Cavallini Claudio, Antonicelli Roberto, Petronio Anna Sonia, Murena Ernesto, Olivari Zoran, Steffenino Giuseppe, Bonechi Francesco, Mafrici Antonio, Toso Anna, Piscione Federico, Bolognese Leonardo, De Servi Stefano
  
  Abstract
  
  OBJECTIVES:
  To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome (ACS).
  
  DESIGN:
  Prospective cohort study.
  
  SETTING:
  Twenty-three hospitals in Italy.
  
  PARTICIPANTS:
  Individuals aged 75 and older with non-ST-elevation ACS (NSTEACS) (mean age 82, 47% female) (N = 645).
  
  MEASUREMENTS:
  Diabetic status and blood glucose levels were assessed on admission. Hyperglycemia was defined as glucose greater than 140 mg/dL. Multivariable Cox proportional hazard regression was used to assess the potential confounding effect of major covariates on the association between diabetic status, admission glucose, and 1-year mortality.
  
  RESULTS:
  A history of diabetes mellitus was found in 231 participants (35.8%), whereas 257 (39.8%) had hyperglycemia. Hyperglycemia was found in 171 participants with diabetes mellitus (70%) and 86 (21%) without diabetes mellitus. Participants with diabetes mellitus were significantly (P < .05) more likely to have had prior myocardial infarction and stroke and had lower ejection fraction and blood hemoglobin. Hyperglycemia was associated with lower (P < .05) ejection fraction and estimated glomerular filtration rate (eGFR). Diabetic status and hyperglycemia were associated with greater 1-year mortality according to univariate analysis (54 participants with diabetes mellitus died (23.4%), versus 66 (15.9%) without diabetes mellitus (hazard ratio (HR) = 1.5 95% confidence interval (CI) = 1.0-2.1), and 60 participants with hyperglycemia died (23.3%), versus 60 (15.5%) without hyperglycemia (HR=1.6; 95% CI = 1.1-2.2), but this association was not statistically significant after adjustment for ejection fraction, age, blood hemoglobin, and eGFR.
  
  CONCLUSION:
  In elderly adults with NSTEACS, diabetes mellitus and hyperglycemia on admission are associated with higher mortality, mostly because of preexisting cardiovascular and renal damage.
  
  © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
  
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• Delayed, severe thrombocytemia after abciximab infusion for primary angioplasty in acute coronary syndromes: Moving between systemic bleeding and stent thrombosis.
  Platelets

  2015 ;26(5):498-500. doi: 10.3109/09537104.2014.898181.
  
  Giupponi Luca, Cantoni Silvia, Morici Nuccia, Sacco Alice, Giannattasio Cristina, Klugmann Silvio, Savonitto Stefano
  
  
  
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• Prasugrel and ticagrelor: is there a winner?
  J Cardiovasc Med (Hagerstown)

  2014 Jan;15(1):8-18. doi: 10.2459/JCM.0b013e328364561b.
  
  Morici Nuccia, Colombo Paola, Mafrici Antonio, Oreglia Jacopo A, Klugmann Silvio, Savonitto Stefano
  
  Abstract
  
  Clopidogrel is a prodrug that undergoes extensive enteric clearance and requires two-stage hepatic activation by cytochrome P450 (CYP) enzymes. This metabolic pathway is susceptible to genetic polymorphisms, resulting in a variable platelet inhibitory effect. A growing number of studies have linked poor antiplatelet response to clopidogrel to adverse clinical outcomes, particularly coronary ischemic events and stent thrombosis. This has prompted the development of new ADP receptor antagonists that inhibit platelets more effectively. Two of these agents, prasugrel and ticagrelor, have been investigated in two large randomized clinical trials, and both have shown superiority versus clopidogrel in reducing ischemic endpoints, with an increase in bleeding events, but a favorable final net clinical outcome. Since the publication of the main articles, several sub-analyses have been performed on the same data, and Guideline recommendations have largely endorsed these subgroup findings. Most clinicians have accepted the concept that we might consider approaching the patient differently, deserving a specific agent for each different settings. However, subgroup analyses of randomized trials are often post hoc, underpowered and prone to bias. Weighing efficacy and safety of the most commonly used antiplatelet agents will represent a clinical challenge over the next few years. Furthermore, individuals and organizations involved in formulary decisions will have to face economic constraints, also taking into account the availability of low-cost generic clopidogrel. In the following review, we have performed a critical appraisal of the current literature in order to outline lights and shadows on the most relevant clinical scenarios.
  
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• Renal function estimation and one-year mortality in elderly patients with non-ST-segment elevation acute coronary syndromes.
  Int J Cardiol

  2014 Jun;174(1):127-8. doi: 10.1016/j.ijcard.2013.12.306.
  
  Morici Nuccia, De Servi Stefano, Toso Anna, Murena Ernesto, Tamburrini Paola, Antonicelli Roberto, del Pinto Maurizio, Cavallini Claudio, Petronio A Sonia, Giannini Cristina, Piscione Federico, Bolognese Leonardo, Savonitto Stefano
  
  
  
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• Reply to letter to the editor: "adenosine di-phosphate receptor antagonist discontinuation management prior to coronary artery surgery".
  Int J Cardiol

  2014 Mar;172(1):221-2. doi: 10.1016/j.ijcard.2013.12.199.
  
  Morici Nuccia, Moja Lorenzo, Rosato Valentina, Savonitto Stefano
  
  
  
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• Bridge with intravenous antiplatelet therapy during temporary withdrawal of oral agents for surgical procedures: a systematic review.
  Intern Emerg Med

  2014 Mar;9(2):225-35. doi: 10.1007/s11739-013-1041-8.
  
  Morici Nuccia, Moja Lorenzo, Rosato Valentina, Sacco Alice, Mafrici Antonio, Klugmann Silvio, D'Urbano Maurizio, La Vecchia Carlo, De Servi Stefano, Savonitto Stefano
  
  Abstract
  
  Patients needing surgery within 1 year after drug-eluting cardiac stent implantation are challenging to manage because of an increased thrombotic and bleeding risk. A "bridge therapy" with short-acting antiplatelet agents in the perioperative period is an option. We assessed the outcome and safety of such a bridge therapy in cardiovascular and non-cardiovascular surgery. We performed a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and ongoing trial registers, irrespective of type of design. Our primary outcome was the success rate of bridge therapy in terms of freedom from cardiac ischaemic adverse events, whereas secondary outcome was freedom from bleeding/transfusion. We also performed combined success rate for each bridge therapy drug (tirofiban, eptifibatide, and cangrelor). We included eight case series and one randomised controlled trial. Among the 420 patients included, the technique was effective 96.2 % of the times [95 % confidence interval (CI) 94.4-98.0 %]. The success rate was 100 % for tirofiban (4 studies), 93.8 % for eptifibatide (4 studies), and 96.2 % for cangrelor (1 study). Freedom from bleeding/transfusion events was observed in 72.6 % of the times (95 % CI 68.4-76.9 %), and was higher with cangrelor (88.7 %; 95 % CI 82.7-94.7 %) than with other drugs (81.0 % for tirofiban and 58.6 % for eptifibatide). Evidence from case series and one randomised controlled trial suggests that, in patients with recent coronary stenting undergoing major surgery, perioperative bridge therapy with intravenous antiplatelet agents is an effective and safe treatment option to ensure low rate of ischaemic events.
  
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• Early invasive versus selectively invasive strategy in patients with non-ST-segment elevation acute coronary syndrome: impact of age.
  Catheter Cardiovasc Interv

  2014 Apr;83(5):686-701. doi: 10.1002/ccd.25307.
  
  Angeli Fabio, Verdecchia Paolo, Savonitto Stefano, Morici Nuccia, De Servi Stefano, Cavallini Claudio
  
  Abstract
  
  BACKGROUND:
  It is unclear whether the benefits of an early invasive strategy (EIS) in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) equally apply to younger and older individuals. Elderly patients are generally less likely to undergo EIS when compared with younger patients.
  
  OBJECTIVES:
  We conducted a meta-analysis to compare the benefit of an EIS versus a selectively invasive strategy (SIS) in patients with NSTEACS. We tested the hypothesis that the magnitude of benefit of an EIS over a SIS mainly applies to older individuals.
  
  METHODS:
  We extracted data from randomized controlled trials (RCTs) identified through search methodology filters. The primary outcome of the analysis was the composite of all-cause death and myocardial infarction (MI). Secondary outcomes were death and MI taken alone and re-hospitalization.
  
  RESULTS:
  Nine trials (n = 9,400 patients) were eligible. The incidence of the composite end-point of MI and all-cause death was 16.0% with the EIS and 18.3% with the SIS (OR: 0.85, 95% CI: 0.76-0.95). The incidence of MI was 8.4% with the EIS and 10.9% with the SIS (OR: 0.75, 95% CI: 0.66-0.87). Similar results were obtained for rehospitalization (OR: 0.71, 95% CI: 0.55-0.90). The incidence of all-cause death did not differ between the two groups. The EIS reduced the composite end-point and re-hospitalization to a greater extent in elderly than in younger patients (P for interaction = 0.044 and <0.0001, respectively). These findings were confirmed in meta-regression analyses.
  
  CONCLUSIONS:
  In patients with NSTEACS, a routine EIS reduces the risk of rehospitalization and the composite end point of recurrent MI and death to a greater extent in elderly than in younger individuals.
  
  Copyright © 2013 Wiley Periodicals, Inc.
  
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• Antiplatelet therapy for patients with stable ischemic heart disease and baseline thrombocytopenia: ask the hematologist.
  Platelets

  2014 ;25(6):455-60. doi: 10.3109/09537104.2013.828029.
  
  Morici Nuccia, Cantoni Silvia, Savonitto Stefano
  
  Abstract
  
  Baseline thrombocytopenia (TP) is relatively common in patients referred for percutaneous coronary intervention (PCI). Its detection may have implications for long-term antiplatelet medication prescription and adherence. The aim of this article is to review several practical aspects in managing patients with baseline TP and stable coronary artery disease (CAD). Moving from two clinical cases, we tried to picture cardiological scenarios associated with baseline TP and to provide flow charts for patient's management which take into consideration both the cardiological and the hematological conditions. TP in patients with stable CAD on antiplatelet treatment may follow diverse clinical courses depending upon TP inferred etiology, baseline degree of thrombocytopenia and its time course as outlined by previous complete blood counts, when available. Evaluation of these three parameters may guide the planning of further patient work-up and the choice of the most appropriate cardiological treatment (medical, invasive with stent implantation or coronary artery bypass). A multidisciplinary evaluation comprehensive of hematological counseling is also recommended in these patients before planning prolonged dual anti-platelet therapy.
  
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• Causes of death in patients ?75 years of age with non-ST-segment elevation acute coronary syndrome.
  Am J Cardiol

  2013 Jul;112(1):1-7. doi: 10.1016/j.amjcard.2013.02.043.
  
  Morici Nuccia, Savonitto Stefano, Murena Ernesto, Antonicelli Roberto, Piovaccari Giancarlo, Tucci Daniele, Tamburino Corrado, Fontanelli Alessandro, Bolognese Leonardo, Menozzi Mila, Cavallini Claudio, Petronio Anna Sonia, Ambrosio Giuseppe, Piscione Federico, Steffenino Giuseppe, De Servi Stefano
  
  Abstract
  
  The causes of death within 1 year of hospital admission in patients with non-ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ?75 years. From January 2008 through May 2010, we enrolled 645 patients aged ?75 years with non-ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non-ST-segment elevation acute coronary syndromes, most deaths in patients aged ?75 years have a cardiac origin, mostly owing to myocardial ischemia.
  
  Copyright © 2013 Elsevier Inc. All rights reserved.
  
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• Acute Coronary Syndrome in Pre- and Post-partum Women - A Review.
  Interv Cardiol

  2013 Mar;8(1):8-13. doi: 10.15420/icr.2013.8.1.8.
  
  Aprigliano Gianfranco, Palloshi Altin, Morici Nuccia, Ferraresi Roberto, Bianchi Michele, Anzuini Angelo
  
  Abstract
  
  Acute coronary syndrome (ACS) during pregnancy and the post-partum period are weighed by a high mortality rate for the mother and foetus. They should be considered as multifactorial diseases with a special role for sexual hormones. In this setting, ACS is mostly related to an early atherosclerotic disease, even if other conditions are responsible. Indeed, an important part is due to spontaneous coronary artery dissection, more common during delivery and the post-partum period. In the remaining situation, an isolated intracoronary thrombus or a normal angiographic pattern can be found at angiography. Pathophysiology is still uncertain with different hypothetical mechanisms. Prompt diagnosis of ACS and aetiology are essential for an optimal therapeutic strategy. Difficulties in treatment management is a matter for debate, especially in pre-partum women. In the last two decades improvements of diagnostic tools, coronary angiography and subsequent percutaneous treatment have changed the natural history of this rare condition.
  
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• Spontaneous left main stem coronary artery dissection in a young postpartum woman.
  J Cardiovasc Med (Hagerstown)

  2017 09;18(9):721-722. doi: 10.2459/JCM.0b013e32835ec7ca.
  
  Aprigliano Gianfranco, Palloshi Altin, Morici Nuccia
  
  
  
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• Time from adenosine di-phosphate receptor antagonist discontinuation to coronary bypass surgery in patients with acute coronary syndrome: meta-analysis and meta-regression.
  Int J Cardiol

  2013 Oct;168(3):1955-64. doi: 10.1016/j.ijcard.2012.12.087.
  
  Morici Nuccia, Moja Lorenzo, Rosato Valentina, Oreglia Jacopo Andrea, Sacco Alice, De Marco Federico, Bruschi Giuseppe, Klugmann Silvio, La Vecchia Carlo, Savonitto Stefano
  
  Abstract
  
  BACKGROUND:
  Adenosine di-phosphate receptor antagonists (ADPRAs) blunt hemostasis for several days after administration. This effect, aimed at preventing cardiac ischemic complications particularly in patients with acute coronary syndromes (ACS), may increase perioperative bleeding in the case of cardiac surgery. Practice Guidelines recommend withholding ADPRAs for at least 5days prior to surgery, though with a weak base of evidence. The purpose of this study was to systematically review observational and experimental studies of early or late preoperative discontinuation of ADPRAs prior to coronary artery bypass grafting (CABG) for patients with ACS.
  
  METHODS:
  MEDLINE, EMBASE, the Cochrane Library databases up to December 2011; and reference lists. Observational and experimental studies that compared early ADPRA discontinuation with late discontinuation, or no discontinuation, in patients with ACS undergoing CABG.
  
  RESULTS:
  There were 19 studies, including 14,046 participants, 395 deaths and 309 reoperations due to bleeding. ADPRA late discontinuation up to CABG was associated with an increased risk of postoperative mortality (OR 1.46, 95% confidence interval (CI) 1.10 to 1.93) and reoperations due to bleeding (OR 2.18; 95% CI 1.47 to 2.62). Between-study heterogeneity was low. Meta-analysis limited to high quality or prospective studies gave consistent results. In most instances, the 95% prediction intervals for summary risk estimates confirmed the risk across study groups.
  
  CONCLUSIONS:
  ADPRA late discontinuation prior to CABG is associated with an increased risk of death and reoperations due to bleeding in patients with ACS. The confidence in the estimates of risk for late discontinuation is moderate to high.
  
  Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
  
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• Heart transplantation: 25 years' single-centre experience.
  J Cardiovasc Med (Hagerstown)

  2013 Sep;14(9):637-47. doi: 10.2459/JCM.0b013e32835dbd74.
  
  Bruschi Giuseppe, Colombo Tiziano, Oliva Fabrizio, Botta Luca, Morici Nuccia, Cannata Aldo, Vittori Claudia, Turazza Fabio, Garascia Andrea, Pedrazzini Giovanna, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  OBJECTIVES:
  Heart transplantation (HTx) is still one of the most effective therapies for end-stage heart disease for patients with no other medical or surgical therapy. We report the results of our 25-year orthotropic HTx single-centre experience.
  
  METHODS:
  From November 1985, 905 orthotopic heart transplants have been performed at our centre. We exclude from the present analysis 13 patients who underwent re-transplantation and 14 pediatric cases (age at HTx <15 years).
  
  RESULTS:
  The present study collected the data of 878 primary adult orthotopic HTx performed at our centre. Mean age at HTx was of 49.6?±?11.6 years. Mean donor age was 36.9?±?14.8 years. Hospital mortality was 11.6% (102 patients), early graft failure was the principal cause of death (58 patients) followed by infections (18 cases) and acute rejection (7 patients). Overall actuarial survival was 78.1% at 5 years and 63.8% and 47.5%, respectively, at 10 and 15 years from HTx. Mean survival was 10.74 years; 257 late deaths were reported (33.1%); main causes were neoplasm in 83 patients, and cardiac causes included coronary allograft vasculopathy in 78 patients. Freedom from any infection at 5, 10 and 15 years was 52.2, 44.1 and 40.1%, respectively. Freedom from rejection at 5 years was 36.2%, with 493 patients experiencing at last one episode of rejection, the majority occurring during the first 2 months after transplantation. The long-term survival of HTx recipients is limited in large part by the development of coronary artery vasculopathy and malignancies. In our experience freedom from coronary allograft vasculopathy at 10 years was 66.9%, and 85 patients underwent percutaneous coronary revascularization. In our study population, 44 patients experienced posttransplant lymphoproliferative disorder and 91 patients experienced a solid neoplasm, mean survival free from neoplasm was 12.23 years.
  
  CONCLUSION:
  Over the past four decades the field of HTx has evolved considerably, with improvements in surgical techniques and postoperative patients' care. A careful patient selection and treatment of candidates for transplantation as well as accurate clinical follow-up combined with real multidisciplinary teamwork that involved different heart failure specialists, allowed us to obtain our excellent long-term results.
  
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• Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial.
  JACC Cardiovasc Interv

  2012 Sep;5(9):906-16. doi: 10.1016/j.jcin.2012.06.008.
  
  Savonitto Stefano, Cavallini Claudio, Petronio A Sonia, Murena Ernesto, Antonicelli Roberto, Sacco Alice, Steffenino Giuseppe, Bonechi Francesco, Mossuti Ernesto, Manari Antonio, Tolaro Salvatore, Toso Anna, Daniotti Alessandro, Piscione Federico, Morici Nuccia, Cesana Bruno M, Jori M Cristina, De Servi Stefano,
  
  Abstract
  
  OBJECTIVES:
  This study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS).
  
  BACKGROUND:
  Elderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS.
  
  METHODS:
  A total of 313 patients ? 75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year.
  
  RESULTS:
  During admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03).
  
  CONCLUSIONS:
  The present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185).
  
  Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Tako-Tsubo like syndrome triggered by meperidine.
  Med J Malaysia

  2011 Dec;66(5):520-1.
  
  Sacco Alice, Morici Nuccia, Belli Oriana, Bossi Irene, Mafrici Antonio, Klugmann Silvio
  
  Abstract
  
  We present a case of "inverted Tako-Tsubo" syndrome in a woman sedated with meperidine before undergoing a colonscopy. We discuss possible etiology of this ventricular dysfunction.
  
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• [Bivalirudin as an anticoagulant during percutaneous coronary interventions in acute coronary syndromes: strengths and doubts].
  Rev Esp Cardiol

  2011 May;64(5):361-4. doi: 10.1016/j.recesp.2011.02.005.
  
  Savonitto Stefano, Morici Nuccia
  
  
  
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• Orthotopic heart transplantation with donors greater than or equal to 60 years of age: a single-center experience.
  Eur J Cardiothorac Surg

  2011 Jul;40(1):e55-61. doi: 10.1016/j.ejcts.2011.02.013.
  
  Bruschi Giuseppe, Colombo Tiziano, Oliva Fabrizio, Morici Nuccia, Botta Luca, Cannata Aldo, Frigerio Maria, Martinelli Luigi
  
  Abstract
  
  OBJECTIVES:
  Heart transplantation is the best therapeutic option for patients suffering from end-stage heart failure, but donor organ availability still represents a major problem. This had led to a shift toward extended donor criteria. The aim of the present study is to analyze the short- and long-term results of heart transplantation in patients with donor age ? 60 years.
  
  METHODS:
  Since November 1985, 890 patients have been transplanted at our center. We consider, for the present study, only primary adult heart transplantations performed after 1990, totaling 761 patients, mean age at transplantation 49.8 years, and 616 patients being male (81%). We compare the short- and long-term results of patients transplanted with donors younger than 60 years or ? 60 years.
  
  RESULTS:
  Since 1990, at our center, 711 patients have been heart transplanted with a donor younger than 60 years, while 50 patients received a heart from a donor older than 60 years. No differences have been reported in the etiology of cardiomyopathy, previous surgery, or mean ischemic time. Patients transplanted with donors ? 60 years of age were significantly older compared to the younger donors' group. Donor cause of death was a cerebrovascular accident in 82% of donors ? 60 years versus 41% in younger donors. Patients' heart transplanted with donors ? 60 years had a higher incidence of acute graft failure with a hospital mortality of 32% (16 patients) significantly higher compared with 10.2% for the other group. No differences were noticed in the incidence of renal failure, acute rejection treated, coronary allograft vasculopathy, and neoplasm during long-term follow-up.
  
  CONCLUSIONS:
  It was possible to expand the cardiac donor pool by accepting allografts from donors ? 60 years of age in selected cases by performing a coronary angiogram. A meticulous donor evaluation and a careful risk assessment between the risk of death on the waiting list and probable increased hospital mortality are needed.
  
  Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
  
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• Epinephrine for acute decompensated heart failure and low output state: friend or foe?
  Int J Cardiol

  2011 Jun;149(3):384-5. doi: 10.1016/j.ijcard.2011.03.006.
  
  Morici Nuccia, Sacco Alice, Oliva Fabrizio, Ferrari Stefano, Paino Roberto, Milazzo Filippo, Frigerio Maria, Pirola Roberto, Klugmann Silvio, Mafrici Antonio
  
  
  
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• Coronary left main and non-left main bifurcation angles: how are the angles modified by different bifurcation stenting techniques?
  J Interv Cardiol

  2010 Aug;23(4):382-93. doi: 10.1111/j.1540-8183.2010.00562.x.
  
  Godino Cosmo, Al-Lamee Rasha, La Rosa Claudio, Morici Nuccia, Latib Azeem, Ielasi Alfonso, Di Mario Carlo, Sangiorgi Giuseppe M, Colombo Antonio
  
  Abstract
  
  BACKGROUND:
  Investigation of the correlation between bifurcation angles and outcomes is limited with discordant results. The aim of this study is to investigate left main (LM) and non-left main (N-LM) bifurcation angles and their modification after percutaneous coronary intervention (PCI). Measurement of all three angles adds to our understanding of bifurcation anatomy and the resultant effect of different stenting techniques.
  
  METHODS AND RESULTS:
  All three bifurcation angles were described according to the European Bifurcation Club definition: the A (proximal bifurcation angle), the B (distal bifurcation angle) and the C (main branch angle). Measurements were performed in 75 LM and 140 N-LM bifurcations. In LM bifurcations baseline mean values of C, A, and B were 151 degrees +/- 28 degrees, 131 degrees +/- 32 degrees, and 78 +/- 28 degrees, respectively. In bifurcations with 2 stents the B significantly decreased by a mean of 10 degrees (P = 0.003) and A increased by 10 degrees (P = 0.006). Crush stenting significantly decreased B (A - 14 degrees ; P = 0.020) and increased A (A + 21 degrees; P = 0.005), particularly non-true bifurcations. In N-LM bifurcations mean values for C, A, and B were 156 degrees +/- 19 degrees , 144 degrees +/- 22 degrees, and 60 degrees +/- 20 degrees, respectively. Similar to LM bifurcations, the B became narrower mainly at the expense of the A, which became wider. In both types of bifurcations the greatest variation in A and B was found following 2-stent techniques performed in T-shaped (> or =70 degrees) bifurcations.
  
  CONCLUSIONS:
  In both LM and N-LM bifurcations we found a significant difference in A and B pre- and post-PCI. This difference was driven by the 2-stent technique and was most evident with a baseline bifurcation angle > or =70 degrees. The Crush technique caused the largest angle variation post-procedure, particularly in non-true LM bifurcations.
  
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• Prolonged double antiplatelet therapy in a cohort of "de novo" diabetic patients treated with drug-eluting stent implantation.
  Am J Cardiol

  2010 May;105(10):1395-401. doi: 10.1016/j.amjcard.2009.12.062.
  
  Mollichelli Nadia, Morici Nuccia, Ambrogi Federico, Latib Azeem, Boracchi Patrizia, Godino Cosmo, Ferri Luca, Ielasi Alfonso, Chieffo Alaide, Montorfano Matteo, Colombo Antonio
  
  Abstract
  
  Diabetes mellitus (DM) accounts for >25% of all percutaneous coronary interventions. In patients with DM, drug-eluting stent implantation is associated with a reduced risk of restenosis and target lesion revascularization. However, concern has been raised about the incidence of late and very late stent thrombosis and the increased mortality rate, mostly after thienopyridine withdrawal. We evaluated the long-term prognostic effect of thienopyridine discontinuation after drug-eluting stent implantation on the subsequent occurrence of stent thrombosis and all-cause death among a cohort of high-risk "de novo" diabetic patients. From May 2002 to December 2005, 542 consecutive patients with DM underwent drug-eluting stent implantation at 2 hospitals in Milan, Italy. For study purposes, only the 217 patients who had not previously undergone percutaneous or surgical revascularization were considered in the final analysis. The follow-up time was curtailed at 3.5 years. Detailed information about dual antiplatelet therapy (DAT) were collected for all patients included. Of the 217 patients, 15 died (6.9%); in 9 cases, the cause of death was cardiac (4.1%). The incidence of cumulative stent thrombosis was 4.6% (10 patients); 3 stent thromboses were early (1.38%), 5 late (2.3%), and only 2 were very late (0.9%). Of the 10 cases of stent thrombosis, 5 were definite and 5 were probable. Most (80%) of the stent thromboses occurred within the first 6 months during DAT. The median duration of DAT was 420 days (interquartile range 350 to 859). DAT discontinuation was the only independent predictor of the follow-up events (hazard ratio 20.42, 95% confidence interval 4.99 to 83.62). In conclusion, DM remains an independent adverse factor on clinical outcome. In this setting, prolonged DAT, even beyond that recommended in the guidelines, might be beneficial.
  
  Copyright 2010 Elsevier Inc. All rights reserved.
  
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• Emergency Medical System response to out-of-hospital cardiac arrest in Milan, Italy.
  Eur J Emerg Med

  2010 Aug;17(4):234-6. doi: 10.1097/MEJ.0b013e328330b3ef.
  
  Morici Nuccia, De Luca Giovanni, Lucenteforte Ersilia, Chatenoud Liliane, Fontana Giancarlo, La Vecchia Carlo, Sesana Giovanni
  
  Abstract
  
  The objective of this study was to investigate how rapidly the Emergency Medical System provides life support to patients suffering out-of-hospital cardiac arrest in Milan, Italy. The study population included 1426 consecutive participants with out-of-hospital cardiac arrest between January 2007 and October 2008. The mean age was 72.7 years. The incidence of ventricular tachycardia/ventricular fibrillation as the presenting rhythm was 12.7%. Eighty percent of out-of-hospital cardiac arrests occurred at home and bystander cardiopulmonary resuscitation (CPR) was in progress in 11.1% of all cases. The mean time interval from collapse-to-first shock was 18.67+/-5.37 min. The mean Emergency Medical System unit response time interval was 7.07+/-3.14 min; time elapsed from arrival-to-first CPR was 7.75+/-4.32 min. In conclusions, the dispatch to arrival and dispatch to CPR intervals are comparable with those reported in other large urban areas, but the time from arrival-to-first CPR was longer than recommended by current guidelines.
  
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• Thin strut chrome-cobalt stent implantation for treatment of de-novo lesions in small coronary vessels: results of the RISICO Italian Registry (Registro Italiano Mini VISION nei piccolo Vasi) utilizing the Mini VISION coronary stent platform.
  J Cardiovasc Med (Hagerstown)

  2009 Nov;10(11):852-8. doi: 10.2459/JCM.0b013e32832e6446.
  
  Brambilla Nedy, Morici Nuccia, Bedogni Francesco, De Benedictis Mauro, Scrocca Innocente, Naldi Monica, Fiscella Antonio, Prosperi Franco, Dominici Mauro, Rebuzzi Antonio, Colombo Antonio, Sangiorgi Giuseppe M,
  
  Abstract
  
  OBJECTIVES:
  The Registro Italiano Mini VISION nei piccoli Vasi registry is a prospective, multicenter, observational study, aimed at assessing immediate and long-term angiographic and clinical outcomes of a small-vessel cobalt-chrome super alloy-dedicated stent (Multi-Link RX VISION) in de-novo and long lesions.
  
  BACKGROUND:
  Small artery size is an important determinant of poor outcomes in percutaneous coronary interventions.
  
  METHODS:
  Patients with ischemic heart disease were included. The primary end point was procedural success. Secondary end points included clinical restenosis (need for target lesion revascularization ), incidence of major adverse cardiac events at 6 months, and cost-effectiveness analysis.
  
  RESULTS:
  Between September 2004 and October 2005, 143 patients (mean age 67 +/- 11 years; 22% diabetes) were enrolled; 6-month follow-up was completed in May 2006. Average lesion length, mean stent length and diameter were 16.8 +/- 7.1, 17.01 +/- 3.9 and 2.41 +/- 0.14 mm, respectively. Procedural success was 96%. At 6-month follow-up, the hierarchical major adverse cardiac event rate was 11.6%, 2.9% deaths, 2.9% myocardial infarction and 5.8% target lesion revascularization. Cost-effectiveness analysis will be reported in a further publication.
  
  CONCLUSION:
  Small-vessel disease treatment with Mini VISION stents permits an elevated procedural success rate with low incidence of clinical restenosis and major adverse cardiac events at mid-term follow-up. Such results require confirmation by means of a randomized controlled study against drug-eluting stents.
  
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• Target populations and relevant therapeutic end points to further improve outcomes in NSTEACS patients.
  Future Cardiol

  2009 Jan;5(1):27-41. doi: 10.2217/14796678.5.1.27.
  
  Savonitto Stefano, Morici Nuccia, Sacco Alice, Klugmann Silvio
  
  Abstract
  
  An aggressive pharmaco-interventional approach has been shown to improve long-term outcome among high-risk patients with acute coronary syndromes without ST-segment elevation (NSTEACS). However, these patients continue to represent a minority among those enrolled in clinical trials, thus precluding the possibility to further improve therapeutic efficacy. Target populations that are not adequately addressed by the majority of therapeutic trials are mainly the elderly and those with reduced renal function, who all show unfavorable outcome after an episode of NSTEACS. In order to allow comparison among different studies, a prerequisite for the planning of meaningful trials should be a uniform definition of the study end points besides mortality, particularly with reference to recurrent myocardial infarction, and rehospitalization owing to cardiovascular instability or severe bleeding. In addition to trial design issues, improvements in the regulatory rules for drug development and in hospital networking conceal significant opportunities to improve treatment of NSTEACS.
  
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• Incidence of bleeding and compliance on prolonged dual antiplatelet therapy (aspirin + thienopyridine) following drug-eluting stent implantation.
  Am J Cardiol

  2008 Dec;102(11):1477-81. doi: 10.1016/j.amjcard.2008.07.038.
  
  Latib Azeem, Morici Nuccia, Cosgrave John, Airoldi Flavio, Godino Cosmo, Brambilla Nedy, Chieffo Alaide, Bonizzoni Erminio, Carlino Mauro, Bedogni Francesco, Montorfano Matteo, Sangiorgi Giuseppe M, Briguori Carlo, Colombo Antonio
  
  Abstract
  
  Prolonged periods of dual antiplatelet therapy (DAT), i.e., aspirin plus a thienopyridine, are currently recommended to prevent late drug-eluting stent (DES) thrombosis. The aim of our study was to determine the risk and predictors of bleeding and compliance associated with such prolongation of DAT. In this observational study we examined 2,355 consecutive patients undergoing successful DES implantation at 4 hospitals in Italy from June 2002 to December 2004. Bleeding events occurring on DAT and warfarin or in the first 30 days after stent implantation were excluded. Median duration of DAT was 209 days (interquartile range 178 to 444) and only 158 patients (6.7%) prematurely discontinued DAT. The overall bleeding rate was 1.9% (45), with major bleeding in 19 (0.8%) and minor bleeding in 26 (1.1%). Independent predictors of bleeding were DAT (hazard ratio 19.8, 95% confidence interval [CI] 3.69 to 106.34, p <0.001) and age >65 years (hazard ratio 2.15, 95% CI 1.16 to 4.00, p = 0.02). In patients on DAT, the incidence rate (30 days to 18 months) of any bleeding event was 2.57 per 100 person-years (95% CI 1.85 to 3.48) and major bleeding was 1.10 per 100 person-years (95% CI 0.65 to 1.74). In conclusion, DAT after DES implantation is well tolerated and associated with a very low risk of major bleeding.
  
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• Sirolimus-eluting and paclitaxel-eluting stents for the treatment of coronary bifurcations.
  Am Heart J

  2008 Oct;156(4):745-50.
  
  Latib Azeem, Cosgrave John, Godino Cosmo, Qasim Asif, Corbett Simon J, Tavano Davide, Morici Nuccia, Cristell Nicole, Chieffo Alaide, Carlino Mauro, Montorfano Matteo, Airoldi Flavio, Colombo Antonio
  
  Abstract
  
  BACKGROUND:
  The aim of the study was to compare the outcomes of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stent implantation in coronary bifurcations treated with either a 1-stent or 2-stent strategy.
  
  METHODS:
  The study used a retrospective cohort analysis of consecutive de novo bifurcations, excluding left main, treated with SES or PES between April 2003 and June 2005.
  
  RESULTS:
  We identified 170 bifurcations in 161 patients treated with SES and 119 bifurcations in 112 patients treated with PES. During a median follow-up of 1,061 days (interquartile range 814-1,314), 43 patients (26.7%) in the SES group and 28 (25.0%) in the PES group had a major adverse cardiac event (P = .78). The angiographic restenosis rate per bifurcation was 20.9% and 25.9%, respectively (P = .41). There was no difference overall in the occurrence of target lesion revascularization (TLR) per bifurcation, 22 with SES (12.9%) and 18 with PES (15.1%), P = .61. The TLR rate was similar for SES and PES in bifurcations treated with 1 stent (6.7% vs 11.4%, P = .40) and in bifurcations treated with both branch stenting (20.0% vs 20.4%, P =1.0).
  
  CONCLUSIONS:
  In this cohort, the long-term clinical outcomes appear similar overall between SES and PES in the treatment of coronary bifurcations irrespective of whether a 1-stent or 2-stent strategy was used.
  
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• Clinical and angiographic follow-up of small vessel lesions treated with paclitaxel-eluting stents (from the TRUE Registry).
  Am J Cardiol

  2008 Oct;102(8):1002-8. doi: 10.1016/j.amjcard.2008.05.052.
  
  Godino Cosmo, Furuichi Shinichi, Latib Azeem, Morici Nuccia, Chieffo Alaide, Romagnoli Enrico, Tamburino Corrado, Barbagallo Rossella, Cera Michela, Antoniucci David, Goktekin Omer, Di Mario Carlo, Reimers Bernard, Grube Eberhard, Airoldi Flavio, Sangiorgi Giuseppe M, Colombo Antonio
  
  Abstract
  
  Several randomized trials have shown that sirolimus-eluting stents and paclitaxel-eluting stents (PES) are effective in reducing restenosis in respect to bare-metal stents, including the subset of small vessels. The objective of this study was to evaluate "real world" angiographic and clinical outcomes of a large series of patients enrolled in the TRUE registry and treated with PES for both small vessel and very small vessel lesions. A consecutive series of 675 patients (926 lesions) with reference vessel diameter <2.75 mm measured by quantitative coronary angiography analysis were analyzed. The primary end point was the rate of angiographic in-stent restenosis and 1-year major adverse cardiac events. In this study 390 lesions were identified as small vessel (reference vessel diameter >or=2.25 and <2.75 mm) and 536 lesions as very small vessel (reference vessel diameter <2.25 mm). Overall in-stent restenosis was 15.5% (n = 96). Compared with small vessel, the very small vessel lesions had more in-stent restenosis (21.7% vs 11.4%, p <0.001) and in-segment restenosis (29.3% vs 22.5%, p = 0.055). The majority of the restenotic lesions (n = 125) were focal (57%, n = 71). At 1 year, cardiac death was 1.6% (n = 11), acute myocardial infarction 0.5% (n = 4.), and the target lesion revascularization 12.8% (n = 86). Cumulative major adverse cardiac events rate was 17.3% (n = 119). The rate of definite and probable stent thrombosis was 0.9% (n = 8). In conclusion, in comparison with historical bare-metal stent controls, this large series of small vessel lesions treated with PES confirms previous results reporting the efficacy of PES in small vessels. The rate of subacute and late stent thrombosis was low in this subgroup of patients.
  
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• Percutaneous treatment of a single saphenous vein graft with two different protection devices.
  J Invasive Cardiol

  2008 Jun;20(6):E180-2.
  
  Bedogni Francesco, Morici Nuccia, Brambilla Nedy
  
  Abstract
  
  Catheter-based intervention in saphenous vein aorto-coronary bypass is an established approach. Even if effective, this treatment can be associated with a high incidence of procedure-related complications, mainly because of distal embolization of atherosclerotic plaque. Both occlusion devices and filter-based protection devices have offered comparable results. In the case described below, two different lesions were treated in the same saphenous vein graft using a filter-based device for the proximal lesion and a proximal occlusion balloon for the distal one.
  
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• Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment.
  Circulation

  2007 Aug;116(7):745-54.
  
  Airoldi Flavio, Colombo Antonio, Morici Nuccia, Latib Azeem, Cosgrave John, Buellesfeld Lutz, Bonizzoni Erminio, Carlino Mauro, Gerckens Ulrich, Godino Cosmo, Melzi Gloria, Michev Iassen, Montorfano Matteo, Sangiorgi Giuseppe Massimo, Qasim Asif, Chieffo Alaide, Briguori Carlo, Grube Eberhard
  
  Abstract
  
  BACKGROUND:
  The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents.
  
  METHODS AND RESULTS:
  A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; P<0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; P=0.92).
  
  CONCLUSIONS:
  Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months.
  
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• Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies.
  Circulation

  2007 Mar;115(10):1211-7.
  
  Briguori Carlo, Airoldi Flavio, D'Andrea Davide, Bonizzoni Erminio, Morici Nuccia, Focaccio Amelia, Michev Iassen, Montorfano Matteo, Carlino Mauro, Cosgrave John, Ricciardelli Bruno, Colombo Antonio
  
  Abstract
  
  BACKGROUND:
  Volume supplementation by saline infusion combined with N-acetylcysteine (NAC) represents an effective strategy to prevent contrast agent-induced nephrotoxicity (CIN). Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN.
  
  METHODS AND RESULTS:
  Three hundred twenty-six consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n=111), sodium bicarbonate infusion plus NAC (n=108), and 0.9% saline plus ascorbic acid plus NAC (n=107). All enrolled patients had serum creatinine > or = 2.0 mg/dL and/or estimated glomerular filtration rate < 40 mL x min(-1) x 1.73 m(-2). Contrast nephropathy risk score was calculated in each patient. In all cases, iodixanol (an iso-osmolar, nonionic contrast agent) was administered. The primary end point was an increase of > or = 25% in the creatinine concentration 48 hours after the procedure (CIN). The amount of contrast media administered (179+/-102, 169+/-92, and 169+/-94 mL, respectively; P=0.69) and risk scores (9.1+/-3.4, 9.5+/-3.6, and 9.3+/-3.6; P=0.21) were similar in the 3 groups. CIN occurred in 11 of 111 patients (9.9%) in the saline plus NAC group, in 2 of 108 (1.9%) in the bicarbonate plus NAC group (P=0.019 by Fisher exact test versus saline plus NAC group), and in 11 of 107 (10.3%) in the saline plus ascorbic acid plus NAC group (P=1.00 versus saline plus NAC group).
  
  CONCLUSIONS:
  The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.
  
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• Predictors of restenosis after treatment of bifurcational lesions with paclitaxel eluting stents: a multicenter prospective registry of 150 consecutive patients.
  Catheter Cardiovasc Interv

  2007 Feb;69(3):416-24.
  
  Di Mario Carlo, Morici Nuccia, Godino Cosmo, Goktekin Omer, Tamburino Corrado, Barbagallo Rossella, Antoniucci David, Grube Eberhard, Airoldi Flavio, Zoccai Giuseppe Biondi, Colombo Antonio, Sangiorgi Giuseppe M
  
  Abstract
  
  OBJECTIVES:
  The aim of the study was the assessment of the clinical, angiographic and procedural characteristics correlated with freedom from adverse events at 1 year in a real life setting of consecutive bifurcation lesions.
  
  BACKGROUND:
  Even if stent implantation has shown to be superior to conventional balloon angioplasty in most coronary lesions, bifurcation treatment with stent implantation both in main and in side branch (SB) still raises controversy.
  
  METHODS:
  We reviewed the results obtained in a prospective multicenter registry of 150 patients with 158 bifurcation lesions involving a SB of sufficient diameter to be treated, if necessary, with a polymer based paclitaxel eluting stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions (75.0%) of the 2 and 1 stent group respectively.
  
  RESULTS:
  At 1-year clinical follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents group (2.7%). Unlike previous reports, revascularization involved the main vessel in the majority of patients (21/150, 14.0%). After an exploratory multivariable analysis the only parameter predictive of target lesion revascularization (TLR) (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR) (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal lumen diameter (MB-MLD).
  
  CONCLUSIONS:
  In a real life setting of consecutive bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents group, and need for target lesion revascularization remain higher than in less complex lesion subgroups treated with PES. No differences in immediate success and TLR were observed between 2 stents and 1 stent groups. The frequently observed suboptimal stent expansion and final MB-MLD predict 1 year revascularization.
  
  (c) 2006 Wiley-Liss, Inc.
  
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• Patterns of restenosis after drug-eluting stent implantation: Insights from a contemporary and comparative analysis of sirolimus- and paclitaxel-eluting stents.
  Eur Heart J

  2006 Oct;27(19):2330-7.
  
  Corbett Simon J, Cosgrave John, Melzi Gloria, Babic Rade, Biondi-Zoccai Giuseppe G L, Godino Cosmo, Morici Nuccia, Airoldi Flavio, Michev Iassen, Montorfano Matteo, Sangiorgi Giuseppe M, Bonizzoni Erminio, Colombo Antonio
  
  Abstract
  
  AIM:
  To evaluate patterns of restenosis following implantation of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) in comparable unselected lesions.
  
  METHODS AND RESULTS:
  We have identified all episodes of restenosis after SES or PES implantation in our institutions between March 2003 and March 2005. Restenosis pattern was classified as focal, diffuse, proliferative, or occlusive. The position of focal restenosis was also categorized as proximal, in-stent, distal, or multi-focal. We have characterized 150 and 149 restenotic lesions in SES and PES groups, respectively. The incidence of diffuse and occlusive restenosis was significantly higher in PES than in SES (47.6 vs. 27.0%, P < 0.001). Multivariable (OR 2.693, 95% CI 1.425-5.089, P = 0.002) and propensity (OR 3.00, 95% CI 1.584-5.672, P < 0.001) analyses confirmed the positive association of PES with non-focal restenosis. For both stents, focal-edge restenosis was significantly more likely to occur proximally than distally (61.0 vs. 16.9%, P < 0.001 for PES and 45.8 vs. 16.8%, P < 0.001 for SES).
  
  CONCLUSION:
  Focal restenosis remains the most common pattern with SES. In contrast, just under half of restenosis in PES is the more severe non-focal pattern. Paradoxically, the majority of focal restenosis occurs at the proximal stent margin for both platforms.
  
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• Elective versus provisional intraaortic balloon pumping in unprotected left main stenting.
  Am Heart J

  2006 Sep;152(3):565-72.
  
  Briguori Carlo, Airoldi Flavio, Chieffo Alaide, Montorfano Matteo, Carlino Mauro, Sangiorgi Giuseppe Massimo, Morici Nuccia, Michev Iassen, Iakovou Ioannis, Biondi-Zoccai Giuseppe, Colombo Antonio
  
  Abstract
  
  BACKGROUND:
  Elective intraaortic balloon pump (IABP) may reduce acute complications during unprotected left main (ULM) stenting. However, few data exist on criteria for elective IABP support during ULM stenting.
  
  METHODS:
  Since January 1993, 219 consecutive patients underwent elective ULM stenting: 69 had elective IABP support (elective IABP group), whereas 150 patients had conventional procedure (conservative group). Criteria for elective IABP support were (1) lesion located in the distal segment of the left main (bifurcation lesion), (2) left ventricular ejection fraction <40%, (3) atherectomy, (4) unstable angina, and (5) critical disease of the right coronary artery. Incidence of intraprocedural major adverse cardiac events (eg, severe hypotension and/or shock, myocardial infarction, urgent bypass surgery, and death) was assessed.
  
  RESULTS:
  Euroscore >6 (identifying high-risk patients) occurred in 38% in the elective IABP group and 13% in the conservative group (P < .001). Severe hemodynamic instability occurred in 12 patients (8%) in the conservative group and in none in the elective IABP group (P = .020). Intraprocedural major adverse cardiac event was higher in the conservative group (9.5% vs 1.5%, P = .032). Elective IABP support (OR 0.08, 95% CI 0.01-0.69, P = .022) and presence of Euroscore >6 plus bifurcation lesion (OR 5.49; 95% CI 1.47-20.51; P = .011) were the independent predictors of intraprocedural events.
  
  CONCLUSIONS:
  Elective IABP may prevent intraprocedural events in elective ULM stenting, especially in patients at higher risk.
  
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• Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience.
  Circulation

  2006 May;113(21):2542-7.
  
  Chieffo Alaide, Morici Nuccia, Maisano Francesco, Bonizzoni Erminio, Cosgrave John, Montorfano Matteo, Airoldi Flavio, Carlino Mauro, Michev Iassen, Melzi Gloria, Sangiorgi Giuseppe, Alfieri Ottavio, Colombo Antonio
  
  Abstract
  
  BACKGROUND:
  Improvements in results with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may extend their use in patients with left main coronary artery (LMCA) stenosis.
  
  METHODS AND RESULTS:
  Two hundred forty-nine patients with LMCA stenosis were treated with PCI and DES implantation (n=107) or coronary artery bypass grafting (CABG) (n=142), in a single center, between March 2002 and July 2004. A propensity analysis was performed to adjust for baseline differences between the two cohorts. At 1 year, there was no statistical difference in the occurrence of death in PCI versus CABG both for the unadjusted (OR=0.291; 95% CI=0.054 to 1.085; P=0.0710) and adjusted analyses (OR=0.331; 95% CI=0.055 to 1.404; P=0.1673). PCI was correlated to a lower occurrence of the composite end points of death and myocardial infarction (unadjusted OR=0.235; 95% CI=0.048 to 0.580; P=0.0002; adjusted OR=0.260; 95% CI=0.078 to 0.597; P=0.0005) and death, myocardial infarction, and cerebrovascular events (unadjusted OR=0.300; 95% CI=0.102 to 0.617; P=0.0004; adjusted OR=0.385; 95% CI=0.180 to 0.819; P=0.01). No difference was detected in the occurrence of major adverse cardiac and cerebrovascular event at the unadjusted (OR=0.675; 95% CI=0.371 to 1.189; P=0.1891) and adjusted analyses (OR=0.568; 95% CI=0.229 to 1.344; P=0.2266).
  
  CONCLUSIONS:
  At 1 year, in this single-center, retrospective experience, there was no difference in the degree of protection against death, stroke, myocardial infarction, and revascularization between PCI with DES and CABG for LMCA disease.
  
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• Sandwich drug-eluting stenting: a novel method to treat high-risk coronary lesions.
  J Invasive Cardiol

  2006 Jan;18(1):2-5.
  
  Morici Nuccia, Cosgrave John, Iakovou Ioannis, Zoccai Giuseppe Biondi, Tassanawiwat Worawut, Montorfano Matteo, Sangiorgi Giuseppe Massimo, Colombo Antonio
  
  Abstract
  
  OBJECTIVES:
  To describe a novel approach to drug-eluting stent (DES) implantation, the sandwich technique, comprised of the simultaneous implantation of two completely overlapping DES in the same target lesion.
  
  BACKGROUND:
  DES effectively prevent restenosis in selected coronary lesions. However, adverse lesion characteristics may detrimentally affect outcomes after DES implantation by means of plaque prolapse, recoil or excessive neointimal hyperplasia.
  
  METHODS:
  From July 2002 to November 2004, the sandwich technique was performed in 10 patients with very high-risk lesions. Two DES of identical size and length were implanted, one inside the other, with almost complete overlap. High-pressure postdilatation (up to 28 atm) was carried out in 6 cases. The endpoints of this preliminary evaluation were: technical feasibility, early (30-day) safety, restenosis rate and freedom from adverse events at 9-month follow up.
  
  RESULTS:
  Procedural and angiographic success was achieved in all cases. At follow-up, there were no deaths, myocardial infarctions or stent thromboses. All patients underwent angiographic follow-up; target lesion revascularization was carried out in 3 patients (30%). Of note, in no case was there evidence of aneurysmal remodeling.
  
  CONCLUSIONS:
  This study suggests that implanting 2 DES, one inside the other in a sandwich fashion, is feasible and apparently safe. This approach could be considered in situations such as plaque prolapse or stent recoil where additional scaffolding may be needed.
  
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• Percutaneous saphenectomy: a potentially dreadful complication of cutting balloon angioplasty in saphenous vein grafts.
  Int J Cardiol

  2006 Jan;106(3):418-9.
  
  Tassanawiwat Worawut, Biondi-Zoccai Giuseppe G L, Sangiorgi Giuseppe, Iakovou Ioannis, Tsagalou Eleutheria, Melzi Gloria, Ge Lei, Morici Nuccia, Corvaja Nicola, Colombo Antonio
  
  Abstract
  
  Vessel perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention and is often associated with the use of atheroablative devices. While effective management means are currently available, such as PTFE-covered stent, pericardiocentesis, and perfusion balloon, a timely and skillful approach is of paramount importance to solve this dreadful complication. We hereby describe a case of saphenous vein graft (SVG) perforation occurring after cutting balloon angioplasty for in-stent restenosis. Despite the immediate occurrence of cardiac arrest due to massive extravasation of contrast in the mediastinum with pericardial tamponade, deep catheter intubation enabled the deployment of two PTFE-covered stents and subsequent sealing of the leak with repeated inflation of a perfusion balloon, while hemopericardium was drained by pericardiocentesis. This clinical vignette emphasizes the role of optimal backup in order to deploy life-saving devices and successfully manage life-threatening pericardial tamponade due to SVG rupture.
  
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• Nephrotoxicity of low-osmolality versus iso-osmolality contrast agents: impact of N-acetylcysteine.
  Kidney Int

  2005 Nov;68(5):2250-5.
  
  Briguori Carlo, Colombo Antonio, Airoldi Flavio, Morici Nuccia, Sangiorgi Giuseppe Massimo, Violante Anna, Focaccio Amelia, Montorfano Matteo, Carlino Mauro, Condorelli Gianluigi, Ricciardelli Bruno
  
  Abstract
  
  BACKGROUND:
  Recent data support that iodixanol, an iso-osmolality contrast agent, is less nephrotoxic than low-osmolality contrast agents when hydration is the only prophylactic strategy used. We evaluated the nephrotoxicity of iso- and low-osmolality contrast agents with prophylactic administration of N-acetylcysteine (NAC) along with hydration.
  
  METHODS:
  Two hundred and twenty-five patients with chronic renal insufficiency (serum creatinine >1.5 mg/dL or an estimated glomerular filtration rate <60 mL/min/1.73 m(2)), referred to our institution for coronary and/or peripheral procedures, were assigned to receive low-osmolality (iobitridol group; N = 115) or iso-osmolality (iodixanol group; N = 110) contrast dye. In all cases prophylactic administration of 0.45% saline intravenously and NAC (1200 mg orally twice daily) was used.
  
  RESULTS:
  Baseline creatinine levels were similar in the 2 groups [iobitridol group = 1.70 (IQR: 1.54-1.98) mg/dL; iodixanol group = 1.73 (IQR: 1.56-2.00) mg/dL, P = 0.33]. The risk score for contrast nephrotoxicity was 5.0 +/- 1.6 in the iobitridol group versus 5.0 +/- 1.8 in the iodixanol group (P = 0.44). Increase of at least 0.5 mg/dL of the creatinine concentration 48 hours after the procedure occurred in 4/115 patients (3.5%) in the iobitridol group and 3/110 patients (2.7%) in the iodixanol group (P = 1.00; OR 0.78; 95% CI 0.17-3.56). Amount of contrast media administration was similar in the 2 groups (iobitridol group = 167 +/- 90 mL; iodixanol group = 164 +/- 82 mL; P = 0.61).
  
  CONCLUSION:
  Nephrotoxicity of iso-osmolality and low-osmolality contrast agents was similar when a prophylactic strategy of hydration plus NAC was utilized.
  
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• Primary repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: a useful approach.
  J Thorac Cardiovasc Surg

  2004 Jan;127(1):193-202.
  
  Abella Raul F, De La Torre Teresa, Mastropietro Gerardo, Morici Nuccia, Cipriani Adriano, Marcelletti Carlo
  
  Abstract
  
  BACKGROUND:
  The ultimate goal of surgical therapy for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is to create unobstructed and separate in series pulmonary and systemic circuits. Our preference has been a 1-stage complete unifocalization technique, avoiding collateral anastomosis with either the native pulmonary arteries or other aortopulmonary collateral vessels.
  
  METHODS AND RESULTS:
  Since 1998, 5 patients (median age 29.6 months) with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have undergone surgical correction, consisting of (1) exclusion of a descending thoracic aortic segment from which all major aortopulmonary collateral arteries originate, and (2) connection of this aortic segment to the native pulmonary artery using an interposition polytetrafluoroethylene conduit. The ventricular septal defect was closed in all patients, and the right ventricle was connected to the unifocalized pulmonary artery with a valved conduit. All patients survived the operation. Two patients required reexploration for postoperative bleeding. One patient remained on mechanical ventilation for 17 days due to a pulmonary infection. During follow-up (12-21 months), no patient required additional interventions. The postoperative right ventricular/left ventricular pressure ratio was 0.55 median. No significant stenosis within the reconstructed pulmonary circuit was identified. All patients remain free of symptoms, requiring no medications.
  
  CONCLUSION:
  Intracardiac repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries can be accomplished by a midline 1-stage repair including complete unifocalization of all pulmonary blood supply without individual collateral anastomosis in selected patients. This approach offers a convenient and satisfactory surgical option.
  
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• Transmural coronary inflammation triggers simultaneous multivessel rupture of unstable plaques.
  Ital Heart J

  2003 Jul;4(7):488-91.
  
  Maresi Emiliano, Midulla Rosalba, Cospite Valentina, Morici Nuccia, Tavormina Rossella, Fazio Giovanni, Orlando Elisabetta, Porcasi Rosanna, Trapanese Caterina, Procaccianti Paolo
  
  Abstract
  
  The authors describe a case of sudden cardiac death caused by the simultaneous multivessel rupture of unstable atherosclerotic plaques, triggered by a transmural inflammatory process (coronaritis). Male subject, 44 years old, apparently in good health until 1 hour before death, when he complained of worsening dyspnea. At autopsy, it was found that the heart weighed 486 g. Evaluation of the coronary arteries revealed the presence of atherosclerotic plaques resulting in a lumen critical stenosis of the left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery, and acute occlusive thrombosis of the LAD and RCA. Transverse sections of the ventricular mass highlighted the presence of eccentric hypertrophy of the left ventricle associated with myocardiosclerosis of the posterior interventricular septum and of the posterior wall of the left ventricle. Histology revealed the presence of a coagulative myocytolysis ascribable to the free walls of the left ventricle, and a focus of lymphocytic-active myocarditis. All coronary arteries were sites of intima fibroatheromatous plaques complicated by rupture and thrombosis within the RCA and LAD and by a transmural infiltrate consisting of macrophages and T-lymphocytes associated with consensual medionecrosis and perineuritis. In conclusion, the present case report confirms the hypothesis that inflammation plays a key role in the onset of acute coronary syndromes as it promotes the formation of an unstable plaque as well as its rupture.
  
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