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1. Long‐term mortality after acute coronary syndromes among patients with normal, mildly reduced, or reduced ejection fraction

Author

Remo H.M. Furtado, Marcela G. Juliasz, Felipe Y.J. Chiu, Livia B.C. Bastos, Talia F. Dalcoquio, Felipe G. Lima, Renato Rosa, Cesar A. Caporrino, Adriadne Bertolin, Paulo R.R. Genestreti, Andre S. Ribeiro, Maria Carolina Andrade, Roberto R.C.V. Giraldez, Luciano M. Baracioli, Thomas A. Zelniker, and Jose C. Nicolau

Subjects
ACS, Long‐term mortality, Left ventricular ejection fraction, Mildly reduced ejection fraction, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims Left ventricular ejection fraction (LVEF) ≤ 40% is a well‐established risk factor for mortality after acute coronary syndromes (ACS). However, the long‐term prognostic impact of mildly reduced ejection fraction (EF) (LVEF 41–49%) after ACS remains less clear. Methods and results This was a retrospective study enrolling patients admitted with ACS included in a single‐centre databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mildly reduced (LVEF 41–49%), and reduced (LVEF ≤ 40%). The endpoint of interest was all‐cause death after hospital discharge. A multivariable Cox model was used to adjust for confounders. A total of 3200 patients were included (1952 with normal EF, 375 with mildly reduced EF, and 873 with reduced EF). The estimated cumulative incidence rates of mortality at 10 years for patients with normal, mildly reduced, and reduced EF were 24.8%, 33.5%, and 41.3%, respectively. After adjustments, the presence of reduced EF was associated with higher mortality compared with normal EF [adjusted hazard ratio (HR) 1.64; 95% confidence interval (CI) 1.36–1.96; P

Published
2023
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2. INTERBLEED: Design of an International Study of Risk Factors for Gastrointestinal Bleeding and Cardiovascular Events After Gastrointestinal Bleeding

Author

Jacqueline Bosch, PhD, Paul Moayyedi, MD, PhD, Marco Alings, MD, PhD, Alvaro Avezum, Jr., MD, PhD, Shrikant I. Bangdiwala, PhD, Alan Barkun, MD, CM, MSc, Federico Cassella, MD, Aloisio Marchi da Rocha, MD, PhD, Irfan Duzen, MD, Robert Enns, MD, Nauzer Forbes, MD, MSc, Leah Hamilton, MSc, Shofiqul Islam, PhD, Mustafa Kilickap, MD, MSc, Paul Kruger, MBBS, Yan Liang, MD, Jose C. Nicolau, MD, Rafael Nunes, MD, PhD, Martin O’Donnell, MD, PhD, Gustavo Oliveira, MD, PhD, Alejandro Rey, MD, Yihong Sun, MD, Thomas Vanassche, MD, Peter Verhamme, MD, Michael Walsh, MD, PhD, Zhenyu Wang, MD, Cynthia Wu, MD, Li Zhao, MD, Jun Zhu, MD, and John W. Eikelboom, MBBS

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding. Methods: INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months. Results: As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls. Conclusions: Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications. Résumé: Contexte: L’hémorragie est l’effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l’hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d’un risque accru d’événements CV. Une réduction du fardeau de l’hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l’hémorragie que des événements indésirables qui surviennent après l’hémorragie. Méthodologie: INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d’hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d’événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d’hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d’hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d’hémorragie GI et d’événements CV et d’autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois. Résultats: En date du 1er avril 2022, l’étude est en cours dans 10 pays et 31 établissements de santé; 2 407 cas et 1 478 témoins ont été recrutés. Conclusions: La connaissance des facteurs de risque d’hémorragie, ainsi que des facteurs de risque d’événements CV et de déclin fonctionnel à la suite d’une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.

Published
2022
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3. Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas

Author

Remo Holanda de Mendonça Furtado, Paulo Rizzo Genestreti, Talia F. Dalçóquio, Luciano Moreira Baracioli, Felipe Galego Lima, André Franci, Roberto R. C. V. Giraldez, Fernando R. Menezes, Aline Gehlen Ferrari, Viviane Moreira Lima, Cesar A. C. Pereira, Carlos Alberto Kenji Nakashima, Rocio Salsoso, Lucas Colombo Godoy, and José C. Nicolau

Subjects
Estatinas, Síndrome Coronariana Aguda, Infarto do Miocárdio, Glicemia, Inibidores de Hidroximetilglutril-CoA Redutases, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Resumo Fundamento O maior risco de se desenvolver diabetes com o uso de estatinas é um desafio para a segurança do uso dessa classe de medicamentos em longo prazo. No entanto, poucos estudos analisaram essa questão durante síndromes coronarianas agudas (SCA). Objetivos Investigar a associação entre início precoce da terapia com estatina e níveis de glicemia em pacientes admitidos com SCA. Métodos Este foi um estudo retrospectivo de pacientes hospitalizados por SCA. Pacientes que nunca haviam usado estatinas foram incluídos e divididos segundo uso ou não de estatina nas primeiras 24 horas de internação. O desfecho primário foi a incidência de hiperglicemia na internação (definida como pico de glicemia > 200mg/dL). Modelos de regressão logística e modelos lineares multivariados foram usados para ajuste quanto a fatores de confusão e um modelo de pareamento por escore de propensão foi desenvolvido para comparações entre os dois grupos de interesses. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. Resultados Um total de 2357 pacientes foram incluídos, 1704 deles alocados no grupo que receberam estatinas e 653 no grupo que não receberam estatinas nas primeiras 24 horas de internação. Após os ajustes, uso de estatina nas primeiras 24 horas foi associado com uma menor incidência de hiperglicemia durante a internação (OR ajustado = 0,61, IC95% 0,46-0,80; p < 0,001) e menor necessidade de uso de insulina (OR ajustado = 0,56, IC 95% 0,41-0,76; p < 0,001). Essas associações mantiveram-se similares nos modelos de pareamento por escore de propensão, bem como após análises de sensibilidade, como exclusão de pacientes que desenvolveram choque cardiogênico, infecção grave ou pacientes que foram a óbito durante a internação hospitalar. Conclusões Entre os pacientes internados com SCA que não receberam estatinas previamente, a terapia precoce com estatina associou-se independentemente com menor incidência de hiperglicemia durante a internação. (Arq Bras Cardiol. 2021; 116(2):285-294)

Published
2021
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5. Health-related quality of life 1–3 years post-myocardial infarction: its impact on prognosis

Author

Satoshi Yasuda, Christopher B Granger, David B Brieger, Karolina Andersson Sundell, Jiyan Chen, Tabassome Simon, Dirk Westermann, Richard Grieve, Stuart Pocock, Ruth Owen, Mauricio G Cohen, Shaun Goodman, José C Nicolau, Katarina Hedman, and Carl Mellström

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective To assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI).Methods The global, prospective, observational TIGRIS Study enrolled 9126 patients 1–3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years’ follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years’ follow-up.Results Among 8978 patients who completed the EQ-5D questionnaire, 52% reported ‘some’ or ‘severe’ problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years’ follow-up.Conclusions Clinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death.Trial registration number ClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).

Published
2021
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6. Factors associated with actively working in the very long-term following acute coronary syndrome

Author

Jose C. Nicolau, Remo H.M. Furtado, Talia F. Dalçóquio, Livia M. Lara, Marcela G. Juliasz, Aline G. Ferrari, Carlos A.K. Nakashima, Andre Franci, Cesar A.C. Pereira, Felipe G. Lima, Roberto R. Giraldez, Rocío Salsoso, Luciano M. Baracioli, and Shaun Goodman

Subjects
Long-Term Post-Hospital Discharge, Return to Work, Acute Coronary Syndrome, Medicine (General), R5-920
Abstract

OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p

Published
2021
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7. Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS‐TIMI 54 Trial

Author

Remo H. M. Furtado, Ramkumar V. Venkateswaran, Jose C. Nicolau, Yared Gurmu, Deepak L. Bhatt, Robert F. Storey, P. Gabriel Steg, Giuglia Magnani, Shinya Goto, Mikael Dellborg, Gabriel Kamensky, Daniel Isaza, Philip Aylward, Per Johanson, and Marc P. Bonaca

Subjects
arrhythmias, caffeine, cardiovascular outcomes, dyspnea, ticagrelor, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76–1.10; P=0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63–0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57–1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56–2.04; P=0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.

Published
2020
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9. Multimorbidity, functional impairment, and mortality in older patients stable after prior acute myocardial infarction: Insights from the TIGRIS registry

Author

Akshay Bagai, Faeez M. Ali, John Gregson, Karen P. Alexander, Mauricio G. Cohen, Karolina Andersson Sundell, Tabassome Simon, Dirk Westermann, Satoshi Yasuda, David Brieger, Shaun G. Goodman, Jose C. Nicolau, Christopher B. Granger, and Stuart Pocock

Subjects
Incidence, Myocardial Infarction, Humans, Multimorbidity, Registries, Comorbidity, General Medicine, Cardiology and Cardiovascular Medicine, Aged
Abstract

Data on the association of multimorbidity and functional impairment with cardiovascular (CV) and non-CV outcomes among older myocardial infarction (MI) patients are limited.Multimorbidity and functional impairment among older MI patients are associated with CV and non-CV mortality.Patients aged ≥65 years, 1-3 years post-MI, and enrolled between June 2013 and Novemeber 2014 from 349 sites in 25 countries in the global TIGRIS registry were categorized by age, number of comorbidities, and presence and degree of functional impairment. Functional impairment was calculated using five-dimension EuroQol based on three domains-mobility, self-care, and usual activities. The association between age, number of comorbid conditions, and degree of functional impairment with 2-year incidence of CV and non-CV death was evaluated using Poisson regression analysis.Older age was associated with higher number of comorbidities and functional impairment; after adjustment, increasing age was significantly associated with non-CV mortality (p = .03) but not CV mortality (p = .38). Greater functional impairment was associated with a higher rate and relatively equal magnitude risk of CV (rate ratios [RR] 1.52, 95% confidence intervals [CI]: 1.29-1.79, per one-step increase) and non-CV mortality (RR 1.42, 95% CI: 1.17-1.73). Multimorbidity was more strongly associated with CV mortality (RR 1.52, 95% CI: 1.38-1.67, per additional comorbidity) versus non-CV mortality (RR 1.29, 95% CI: 1.14-1.47, per additional comorbidity).Multimorbidity and functional impairment are prevalent among older post-MI patients and are associated with increased CV and non-CV mortality. These findings highlight the importance of considering comorbid conditions and functional impairment as predictors of risk for adverse outcomes and aspects of medical decision making. Clinical Trial Registration: NCT01866904.

Published
2022
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10. Morphine and clinical outcomes in patients with ST segment elevation myocardial infarction treated with fibrinolytic and antiplatelet therapy: Insights from the TREAT trial

Author

Warren J. Cantor, Mary Tan, Otavio Berwanger, Shahar Lavi, Harvey D. White, Jose C. Nicolau, Payam Dehghani, Carlos D. Tajer, Renato D. Lopes, Diogo D.F. Moia, Stephen J. Nicholls, Alexander Parkhomenko, Oleg Averkov, Neil Brass, Sohrab Lutchmedial, Germán Malaga, Lucas P. Damiani, Leopoldo S. Piegas, Christopher B. Granger, and Shaun G. Goodman

Subjects
Ticagrelor, Morphine, fibrinolytic, Hemorrhage, patients, clinical outcomes, antiplatelet therapy, Clopidogrel, Percutaneous Coronary Intervention, Treatment Outcome, myocardial infarction, ST segment, Humans, ST Elevation Myocardial Infarction, Thrombolytic Therapy, Cardiology and Cardiovascular Medicine, Platelet Aggregation Inhibitors
Abstract

Background: Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor. Methods: In the Ticagrelor in Patients with ST Elevation Myocardial Infarction Treated with Pharmacological Thrombolysis (TREAT) study, 3799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting. Results: Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, P = .0006) and 30 days (HR 1.7, P = .04), and lower hazard of major bleeding (HR 0.37, P = .006). There was no significant difference in mortality at any time point. Conclusions: Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality.

Published
2022
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11. categoria político cultural de amefricanidade como tensionamento afrodiásporico à identidade nacional brasileira

Author

Sofia Maria C. Nicolau and Steffane P. Santos

Abstract

O presente trabalho busca tensionar a formação da identidade nacional brasileira, tendo em vista seu profundo alicerce colonial, calcado na ideologia de branqueamento e na democracia racial. Para isso, acionamos a categoria amefricanidade, desenvolvida por Lélia Gonzalez, como tensionamento à narrativa hegemônica da constituição cultural do povo brasileiro e consequentemente sua identidade nacional, inserindo a importância da diáspora negra nas dinâmicas de formações culturais dentro e fora das fronteiras do Estado brasileiro. Assim, o trabalho em tela explora a tentativa de estabelecimento de uma identidade nacional brasileira a partir de processos homogeneizantes de assimilação cultural, que suprimiram identidades negras e indígenas. Com isso, resgatamos aspectos da formação cultural brasileira a partir de uma influência amefricana, transpassando, com isso, as fronteiras do estado-nação. Encaramos com a categoria político-cultural ds amefricanidade como de resgate de uma América Latina e um Brasil que não tem como base sua formação apenas a influência europeia, mas antes de tudo, seu alicerce negro e indígena.

Published
2022
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12. Rationale and design of a study to assess the safety and efficacy of rNAPc2 in COVID-19: the Phase 2b ASPEN-COVID-19 trial

Author

Connie N. Hess, Warren H. Capell, Michael R. Bristow, Wolfram Ruf, Michael Szarek, David A. Morrow, Jose C. Nicolau, Christopher A. Graybill, Debra Marshall, Judith Hsia, and Marc P. Bonaca

Subjects
Treatment Outcome, SARS-CoV-2, Heparin, Trial Designs, antithrombotic therapy, Anticoagulants, COVID-19, Humans, Prospective Studies, outcomes, Cardiology and Cardiovascular Medicine
Abstract

Background The interaction between thrombosis and inflammation appears central to COVID-19-associated coagulopathy and likely contributes to poor outcomes. Tissue factor is a driver of disordered coagulation and inflammatory signaling in viral infections and is important for viral replication; therefore, tissue factor may be an important therapeutic target in COVID-19. Study Design ASPEN-COVID-19 (NCT04655586) is a randomized, prospective open-label blinded endpoint (PROBE), active comparator Phase 2b trial to evaluate the safety and efficacy of recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent tissue factor inhibitor, in patients hospitalized with COVID-19 with elevated D-dimer levels. This report describes the design of the Phase 2b dose ranging and proof of concept study. Participants are randomly assigned, in a 1:1:2 ratio, to lower or higher dose rNAPc2 by subcutaneous injection on days 1, 3, and 5 or to heparin according to local standard of care; randomization is stratified by baseline D-dimer level (at 2X upper limit of normal). The primary efficacy endpoint for Phase 2b is proportional change in D-dimer concentration from baseline to Day 8 or day of discharge, whichever is earlier. The primary safety endpoint is major or non-major clinically relevant bleeding through Day 8. Phase 2b enrollment began in December 2020 and is projected to complete ∼160 participants by Q4 2021. Conclusions ASPEN-COVID-19 will provide important data on a novel therapeutic approach that may improve outcomes in hospitalized COVID-19 patients beyond available anticoagulants by targeting tissue factor, with potential effects on not only thrombosis but also inflammation and viral propagation.

Published
2022
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13. Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS–TIMI 54

Author

Marc P. Bonaca, Stephen D. Wiviott, David A. Morrow, P. Gabriel Steg, Christian Hamm, Deepak L. Bhatt, Robert F. Storey, Marc Cohen, Julia Kuder, KyungAh Im, Giulia Magnani, Andrzej Budaj, José C. Nicolau, Alexander Parkhomenko, José López‐Sendón, Mikael Dellborg, Rafael Diaz, Frans Van de Werf, Ramón Corbalán, Assen Goudev, Eva C. Jensen, Per Johanson, Eugene Braunwald, and Marc S. Sabatine

Subjects
antiplatelet therapy, myocardial infarction, ST‐segment elevation myocardial infarction, ticagrelor, troponin, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow‐up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for

Published
2018
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14. Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction

Author

Marco Antonio Scanavini-Filho, Otavio Berwanger, Wilson Matthias, Miguel O. Aguiar, Hsu P. Chiang, Luciene Azevedo, Luciano M. Baracioli, Felipe G. Lima, Remo H. M. Furtado, Talia F. Dalcoquio, Fernando R. Menezes, Aline G. Ferrari, Fabio de Luca, Robert P. Giugliano, Shaun Goodman, and José C. Nicolau

Subjects
Pharmacology (medical), General Medicine
Published
2022
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15. Serial Assessment of High-Sensitivity Cardiac Troponin and the Effect of Dapagliflozin in Patients With Heart Failure With Reduced Ejection Fraction

Author

Pardeep S. Jhund, Kieran F. Docherty, Marc S. Sabatine, Eileen O'Meara, Daniel Lindholm, David A. Morrow, John J.V. McMurray, Petr Jarolim, Paul Welsh, Jose C. Nicolau, Naveed Sattar, AM Langkilde, Mikhail Kosiborod, Mikaela Sjöstrand, Vijay K. Chopra, Morten Schou, Ann Hammarstedt, David D. Berg, Inder S. Anand, Rudolf A. de Boer, and Cardiovascular Centre (CVC)

Subjects
Male, medicine.medical_specialty, BIOMARKERS, heart failure, Placebo, GUIDELINES, Ventricular Function, Left, Ventricular Dysfunction, Left, chemistry.chemical_compound, Glucosides, Physiology (medical), Internal medicine, medicine, Clinical endpoint, sodium-glucose transporter 2 inhibitors, Humans, Benzhydryl Compounds, Dapagliflozin, Aged, Proportional Hazards Models, Aged, 80 and over, Clinical Trials as Topic, Ejection fraction, business.industry, troponin, NATRIURETIC PEPTIDE, Hazard ratio, Absolute risk reduction, Stroke Volume, clinical trial, Middle Aged, medicine.disease, PROGNOSTIC VALUE, Quartile, chemistry, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Numbers Needed To Treat
Abstract

Background: Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels. Methods: DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored. Results: Median baseline hsTnT concentration was 20.0 (25th–75th percentile, 13.7–30.2) ng/L. Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46–4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT ( P -interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%–14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, –3% [–6% to 0%]; P =0.076). Conclusions: Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Published
2022
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17. Position Statement on Hypertension and Spirituality – 2021

Author

Sérgio Lívio Menezes Couceiro, Pedro Pimenta de Mello Spineti, Fernando A. Lucchese, Emílio Hideyuki Moriguchi, Eduardo Costa Duarte Barbosa, Ricardo Mourilhe-Rocha, Mario Henrique Elesbão de Borba, Hermilo Borba Griz, Paulo César Brandão Veiga Jardim, Lucélia Batista Neves Cunha Magalhães, Weimar Kunz Sebba Barroso, Andréa Araujo Brandão, Roberto Esporcatte, Alvaro Avezum, Marco A. Mota-Gomes, Roberto Dischinger Miranda, Celso Amodeo, Audes D. M. Feitosa, Fernando Nobre, Jose C. Nicolau, and Mauro Ricardo Nunes Pontes

Subjects
Position statement, business.industry, RC666-701, Hypertension, Humans, Diseases of the circulatory (Cardiovascular) system, Medicine, Spirituality, Posicionamento, Statement, Cardiology and Cardiovascular Medicine, business, Humanities
Abstract

Conceitos Basicos sobre Espiritualidade e suas Formas de Avaliacao As definicoes de espiritualidade e religiosidade apresentam variacoes com o meio cultural, ambiental e religioso. A diversidade de conceitos e reconhecida, sem uma clara definicao, sendo o termo usado de forma imprecisa e inconsistente com consequente dificuldade de medida. Para o Departamento de Estudos em Espiritualidade e Medicina Cardiovascular (DEMCA) da Sociedade Brasileira de Cardiologia (SBC), “Espiritualidade e um conjunto de valores morais, mentais e emocionais que norteiam pensamentos, comportamentos e [...]

Published
2021
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18. Cooling as an Adjunctive Therapy to Percutaneous Intervention in Acute Myocardial Infarction: COOL-MI InCor Trial

Author

Natali Schiavo Giannetti, Michael W. Dae, Sergio Timerman, Claudia Yanet Bernoche San Martin, Roberto Kalil Filho, Jose C. Nicolau, Carlos E. Rochitte, Felipe Gallego Lima, Pedro Alves Lemos Neto, Thatiane Facholi Polastri, Mucio Tavares de Oliveira, Expedito Eustáquio Ribeiro da Silva, Luís Augusto Palma Dallan, and Ludhmila Abrahão Hajjar

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Time Factors, Percutaneous, medicine.medical_treatment, Myocardial Infarction, Critical Care and Intensive Care Medicine, Ventricular Function, Left, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Hypothermia, Induced, Intervention (counseling), Internal medicine, Humans, Medicine, In patient, Prospective Studies, Myocardial infarction, Aged, business.industry, Percutaneous coronary intervention, Stroke Volume, 030208 emergency & critical care medicine, Middle Aged, Hypothermia, medicine.disease, Treatment Outcome, Anesthesiology and Pain Medicine, Cardiology, medicine.symptom, business, Reperfusion injury, 030217 neurology & neurosurgery
Abstract

Endovascular Therapeutic hypothermia (ETH) reduces the damage caused by postischemia reperfusion injury syndrome in cardiopulmonary arrest and has already established its role in patients with sudden death; however, its role in ST-segment elevation myocardial infarction (STEMI) remains controversial. The objectives of this study were to investigate the safety, feasibility, and 30-day efficacy of rapid induction of therapeutic hypothermia as adjunctive therapy to percutaneous coronary intervention (PCI) in patients with anterior and inferior STEMIs. This was a prospective, controlled, randomized, two-arm, prospective, interventional study of patients admitted to the emergency department within 6 hours of angina onset, with anterior or inferior STEMI eligible for PCI. Subjects were randomized to the hypothermia group (primary PCI+ETH) or to the control group (primary PCI) at a 4:1 ratio. The ETH was induced by 1 L cold saline (1-4°C) associated with the Proteus™ System, by cooling for at least 18 minutes before coronary reperfusion with a target temperature of 32°C ± 1°C. Maintenance of ETH was conducted for 1-3 hours, and active reheating was done at a rate of 1°C/h for 4 hours. Primary safety outcomes were the feasibility of ETH in the absence of (1) door-to-balloon (DTB) delay; (2) major adverse cardiac events (MACE) within 30 days after randomization. The primary outcomes of effectiveness were infarct size (IS) and left ventricular ejection fraction (LVEF) at 30 days. An as-treated statistical analysis was performed. Fifty patients were included: 35 (70%) randomized to the hypothermia group and 15 (30%) to the control group. The mean age was 58 ± 12 years; 78% were men; and associated diseases were 60% hypertension, 42% diabetes, and 72% dyslipidemia. The compromised myocardial wall was anterior in 38% and inferior in 62%, and the culprit vessels were left anterior descending artery (LAD) (40%), right coronary artery (38%), and left circumflex (18%). All 35 patients who attempted ETH (100%) had successful cooling, with a mean endovascular coronary reperfusion temperature of 33.1°C ± 0.9°C. The mean ischemic time was 375 ± 89.4 minutes in the hypothermia group and 359.5 ± 99.4 minutes in the control group. The mean DTB was 92.1 ± 20.5 minutes in the hypothermia group and 87 ± 24.4 minutes in the control group. The absolute difference of 5.1 minutes was not statistically significant (

Published
2021
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19. Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Author

Nicolas Diotel, Thierry D. Charlier, Christian Lefebvre d'Hellencourt, David Couret, Vance L. Trudeau, Joel C. Nicolau, Olivier Meilhac, Olivier Kah, and Elisabeth Pellegrini

Subjects
aromatase, cholesterol, blood-brain barrier, estrogens, HDL, lipoproteins, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa) and document their effects on the blood-brain barrier (BBB) permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

Published
2018
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20. Predictors of subclinical carotid atherosclerosis in middle-aged women.

Author

Isly L de Barros, Laura Costa, Bento Bezerra, Rafael Gomes, Natanael Morais, Célia M C Strunz, Moacir Novaes, Otávio C E Gebara, Rodrigo Pinto Pedrosa, and José C Nicolau

Subjects
Medicine, Science
Abstract

BACKGROUND:Traditional strategies for primary cardiovascular prevention have been insufficient in reducing the high rates of coronary ischemic events in women, probably because these women are often stratified into low-risk groups. However, cardiovascular diseases continue to be the main cause of morbidity and mortality in women worldwide. We hypothesized that carotid atherosclerosis (CA) is common in middle-aged women. METHODS:We prospectively evaluated asymptomatic peri- and post-menopausal women with no cardiovascular diseases or the use of hormone therapy from two gynecologic clinics. All the patients underwent full clinical and laboratory evaluation and underwent a B-mode ultrasound for carotid evaluations. The presence of CA was defined as the presence of plaque and/or carotid intima-media thickness (CIMT)>1.00 mm. We performed logistic regression to evaluate independent predictors of CA. RESULTS:We studied 823 women (age: 54.4±5.4 years; body mass index-BMI: 28.5±4.9 kg/m2; diabetes:10%; hypertension: 58%). The prevalence of CA was 12.7% for the entire population and 11% for the low-risk sub-group as defined by a Framingham risk score

Published
2018
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21. Abstract 10464: In-Hospital and Long-Term Impact of Right and Left Bundle-Branch Block in Mortality in Patients With Acute Myocardial Infarction

Author

Jose C Nicolau, Adriadne Bertolin, Marcela Juliasz, FELIPE CHIU, Luciano Baracioli, Felipe Lima, Roberto R Giraldez, Cesar Pereira, Maria Andrade, Andre Ribeiro, Nádia Quintanilha, Glaylton Santos, Cristhian V Espinoza, and Remo Furtado

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: There are scarce data in the literature analyzing, in patients with acute myocardial infarction (AMI), the impact of right (RBBB) and left bundle-branch block (LBBB) on mortality, especially in the long-run after hospital discharge. Hypothesis: RBBB and LBBB is associated with in-hospital and long-term mortality in patients with AMI. Methods: Retrospective analysis from an administrative databank of patients (pts) with acute coronary syndromes, collected prospectively between 1998 and 2016. From a total of 6466 pts, we selected 2895 with AMI (72% men, mean age 63.7 years, 50% with ST-segment-elevation AMI) and complete follow-up for up to 17 years (mean 5.5 years). In-hospital and long-term mortality was compared with RBBB (incidence=5.8%) and LBBB (incidence=3.9%) in models unadjusted and adjusted for 14 variables including age, type/location of AMI and in-hospital cardiogenic shock. Results: In-hospital mortality was 15.5% vs. 7.0% for pts with or without RBBB, respectively (OR=2.41, P Conclusions: After adjustments, there was no association between RBBB or LBBB with higher in-hospital death among patients with AMI. On the other hand, in the long-term follow-up LBBB, but not RBBB, showed significant and independent association with higher mortality.

Published
2022
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23. Results of an international crowdsourcing survey on the treatment of non-ST segment elevation ACS patients at high-bleeding risk undergoing percutaneous intervention

Author

Juan Carlos Kaski, Mirvat Alasnag, Jose C. Nicolau, Sean Delaney, Diana A. Gorog, Marco Valgimigli, John J McNeil, Doreen S.H. Tan, Mamas A. Mamas, Juan Tamargo, Philippe Gabriel Steg, Felicita Andreotti, Deepak L. Bhatt, Dominick J. Angiolillo, Alberto J. Lorenzatti, and Albert Ferro

Subjects
medicine.medical_specialty, Percutaneous, medicine.medical_treatment, 030204 cardiovascular system & hematology, Crowdsourcing, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Surveys and Questionnaires, Intervention (counseling), Humans, Medicine, ST segment, 030212 general & internal medicine, Acute Coronary Syndrome, business.industry, Percutaneous coronary intervention, Elevation (emotion), Treatment Outcome, Emergency medicine, Purinergic P2Y Receptor Antagonists, Drug Therapy, Combination, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors
Abstract

Choosing an antiplatelet strategy in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) at high bleeding risk (HBR), undergoing post-percutaneous coronary intervention (PCI), is complex. We used a unique open-source approach (crowdsourcing) to document if practices varied across a small, global cross-section of antiplatelet prescribers in the post-PCI setting.Five-hundred and fifty-nine professionals from 70 countries (the 'crowd') completed questionnaires containing single- or multi-option and free form questions regarding antiplatelet clinical practice in post-PCI NSTE-ACS patients at HBR. A threshold of 75% defined 'agreement'. There was strong agreement favouring monotherapy with either aspirin or a P2YThe crowdsourcing methodology showed potential as a tool to assess current practice and variation on a global scale and to achieve a broad demographic representation. These preliminary results indicate a high degree of variation with respect to duration of DAPT, monotherapy drug of choice following DAPT and how thrombotic and bleeding risk are assessed. Further investigations should concentrate on interrogating practice variation between key demographic groups.

Published
2021
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24. Diretrizes da Sociedade Brasileira de Cardiologia sobre Angina Instável e Infarto Agudo do Miocárdio sem Supradesnível do Segmento ST – 2021

Author

Manoel Fernandes Canesin, João Luiz de Alencar Araripe Falcão, Luís Alberto Oliveira Dallan, José A Marin Neto, Carlos J.D.G. Barbosa, Harry Correa Filho, Francisco das Chagas Monteiro Júnior, Oscar Pereira Dutra, Pedro Alves Lemos Neto, Euler Roberto Fernandes Manenti, Jose C. Nicolau, José Maria Peixoto, Leonardo Sara da Silva, Bruno Mendonça Baccaro, Paulo Leães, Sandra Nívea dos Reis Saraiva Falcão, Talia Dalcoquio, Remo H.M. Furtado, Renato Jorge Alves, Cláudio Marcelo Bittencourt das Virgens, Otávio Rizzi Coelho, Mucio Tavares de Oliveira Junior, Paulo R. Soares, Luís Augusto Palma Dallan, Dalton Bertolim Précoma, Walmor Lemke, Louis Nakayama Ohe, Viviana de Mello Guzzo Lemke, Andre Franci, Pedro Silvio Farsky, Marcos José Gomes Magalhães, Wilson Mathias Junior, Juliana Ascenção de Souza, Luiz Bezerra Neto, Luiz Alberto Mattos, Brivaldo Markman Filho, Ari Timerman, Luiz Eduardo Fonteles Ritt, Joberto Pinheiro Sena, Marcelo Bueno da Silva Rivas, Roberto Esporcatte, Carlos Eduardo Lucena Montenegro, Edson Stefanini, Rui Fernando Ramos, Ibraim Pinto, Marcelo Franken, Luciano Moreira Baracioli, Eduardo Cavalcanti Lapa Santos, Alexandre Jorge de Andrade Negri, Carlos E. Rochitte, Nivaldo Menezes Filgueiras Filho, Alexandre de Matos Soeiro, Ronaldo de Souza Leão Lima, Renato D. Lopes, Luiz Carlos Bodanese, William Azem Chalela, João Luiz Fernandes Petriz, Bruno Ferraz de Oliveira Gomes, Renato A. K. Kalil, Roberto Luiz Marino, Lilia Nigro Maia, Paulo Roberto Ferreira Rossi, Rafael Rebêlo C. Cavalcanti, Romeu Sergio Meneghelo, Roberto R. Giraldez, Leopoldo S. Piegas, Felipe Gallego Lima, Gilson Soares Feitosa Filho, and Henrique Patrus Mundim Pena

Subjects
SciELO, medicine.medical_specialty, business.industry, Cardiology, Myocardial Infarction, Diretrizes, Guidelines, medicine.disease, Angina, Electrocardiography, RC666-701, Internal medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Medicine, Angina, Unstable, Cardiology and Cardiovascular Medicine, business, Brazil
Abstract

Diretrizes da Sociedade Brasileira de Cardiologia sobre Angina Instavel e Infarto Agudo do Miocardio sem Supradesnivel do Segmento ST – 2021

Published
2021
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25. Platelet Reactivity and Coagulation Markers in Patients with COVID-19

Author

Rinaldo Focaccia Siciliano, Adriadne Justi Bertolin, Felipe G. Lima, Ludhmila Abrahão Hajjar, Roberto R. Giraldez, Rocio Salsoso, Jose C. Nicolau, Alexandra Vieira, Talia Dalcoquio, Cyrillo Cavalheiro-Filho, Remo H.M. Furtado, Esper G. Kallas, Luciano Moreira Baracioli, Celia Maria Cassaro Strunz, Robert P. Giugliano, Roberto Kalil-Filho, Paul A. Gurbel, and Udaya S. Tantry

Subjects
Blood Platelets, medicine.medical_specialty, Platelet Aggregation, Fibrinogen, Gastroenterology, chemistry.chemical_compound, Internal medicine, medicine, Humans, Pharmacology (medical), Platelet, Original Research, business.industry, SARS-CoV-2, Thromboelastometry, Case-control study, COVID-19, General Medicine, Rheumatology, chemistry, Plasminogen activator inhibitor-1, Case-Control Studies, Etiology, Platelet aggregation inhibitor, Multiplate electrode aggregometry, business, Platelet reactivity, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Introdution COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. Methods Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as

Published
2021

26. Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

Author

Michael Böhm, Søren Lund Kristensen, Scott D. Solomon, Marc S. Sabatine, Mark C. Petrie, Morten Schou, Kieran F. Docherty, Piotr Ponikowski, Lars Køber, Daniel Lindholm, Anna Maria Langkilde, Tzvetana Katova, Jose C. Nicolau, Rudolf A. de Boer, Silvio E. Inzucchi, Pardeep S. Jhund, Mikaela Sjöstrand, Mikhail Kosiborod, Olof Bengtsson, Eileen O'Meara, M. Felipe A. Martinez, Li Shen, and John J.V. McMurray

Subjects
medicine.medical_specialty, Ejection fraction, business.industry, Hazard ratio, Renal function, 030204 cardiovascular system & hematology, medicine.disease, Placebo, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Blood pressure, chemistry, Internal medicine, Heart failure, Clinical endpoint, Cardiology, Medicine, 030212 general & internal medicine, Dapagliflozin, Cardiology and Cardiovascular Medicine, business
Abstract

Objectives The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. Background MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. Methods A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. Results A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. Conclusions Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124 )

Published
2021
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27. Effects of DPP4 Inhibitor in Platelet Reactivity and Other Cardiac Risk Markers in Patients with Type 2 Diabetes and Acute Myocardial Infarction

Author

Paulo R. Rizzo Genestreti, Remo H. M. Furtado, Rocio Salsoso, Talia F. Dalçóquio, Andre Franci, Fernando R. Menezes, Cesar Caporrino, Aline G. Ferrari, Carlos A. K. Nakashima, Marco A. Scanavini Filho, Felipe G. Lima, Roberto R. C. V. Giraldez, Luciano M. Baracioli, and Jose C. Nicolau

Subjects
acute myocardial infarction, BNP, biomarkers, DPP4 inhibitors, platelets, platelet reactivity, type 2 diabetes, General Medicine
Abstract

Background: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers. Methods: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint). Results: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity (p = 0.51) between the DPP-4i (8.00 {−65.00; 63.00}) and placebo (−14.00 {−77.00; 52.00}) groups, as well in mean BNP levels (p = 0.14) between DPP-4i (−36.00 {−110.00; 15.00}) and placebo (−13.00 {−50.00; 27.00}). There was no difference between groups in cardiac adverse events. Conclusions: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Published
2022

28. The O-RADS MRI score for the characterization of indeterminate ovarian masses: From theory to practice

Author

C. Sebastià, L. Cabedo, P. Fusté, M. Muntmany, and C. Nicolau

Subjects
Ovarian Neoplasms, General Earth and Planetary Sciences, Humans, Female, Magnetic Resonance Imaging, General Environmental Science
Abstract

This article reviews the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for the characterization of indeterminate ovarian masses. We aim to provide sufficient information to enable readers to apply the score efficiently in clinical practice. To this end, we review the indications of the O-RADS MRI score and the specific MRI protocol that must be applied. We review all the categories of the score, illustrating them through examples. Finally, we show the most common errors and pitfalls during the learning curve, providing the keys to avoiding them.

Published
2022

29. The Impact of Sonothrombolysis on Left Ventricular Diastolic Function and Left Atrial Mechanics Preventing Left Atrial Remodeling in Patients with ST Elevation Acute Myocardial Infarction

Author

Hsu Po Chiang, Miguel O.D. Aguiar, Bruno G. Tavares, Vitor E.E. Rosa, Sergio Barros Gomes, Mucio T. Oliveira, Alexandre Soeiro, Jose C. Nicolau, Henrique B. Ribeiro, João C. Sbano, Carlos E. Rochitte, Roberto Kalil Filho, Jose A.F. Ramires, Thomas R. Porter, Wilson Mathias, and Jeane M. Tsutsui

Subjects
Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Abstract

The diagnostic ultrasound-guided high mechanical index (MI) impulses during an intravenous microbubble infusion (sonothrombolysis) improves myocardial perfusion in acute ST segment elevation myocardial infarction (STEMI), but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling are unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics.100 patients (59±10 years; 34% women) were randomized to receive either high MI impulses plus percutaneous coronary intervention (PCI) (therapy group), or receive PCI only (control group) (n=50 in each group). DD grade and LA mechanics were assessed immediately before and after PCI, 48-72 hours, 1 month and 6 months of follow-up. DD grades were classified as grade I, II and III. The LA mechanics was obtained by 2-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS).As follow-up time progressed, increased DD grade was observed more frequently in the control group than the therapy at 1 month and 6 months of follow-up (all P0.05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48-72 hours, 24.0±7.3 in therapy group vs 19.6%±7.2% in control group, P=0.005; at 1 month, 25.3±6.3 in therapy group vs 21.5% ± 8.3% in control group, P=0.020; and at 6 months, 26.2±8.7 in therapy group vs 21.6%±8.5% in control group, P = 0.015. The therapy group were less likely to experience LA remodeling (OR, 2.91 [1.10 to 7.73]; P=0.03). LA-GLS was the sole predictor of LA remodeling (OR, 0.79 [0.67 to 0.94]; P=0.006).Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling.

Published
2022

30. Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas

Author

Andre Franci, Talia Dalcoquio, Paulo Genestreti, Remo H.M. Furtado, Luciano Moreira Baracioli, Cesar A. C. Pereira, Rocio Salsoso, Felipe G. Lima, Roberto R. Giraldez, Viviane Lima, Lucas C. Godoy, Jose C. Nicolau, Carlos A.K. Nakashima, Fernando Menezes, and Aline Ferrari

Subjects
Blood Glucose, medicine.medical_specialty, Myocardial Infarction, Inibidores de Hidroximetilglutril-CoA Redutases, 030204 cardiovascular system & hematology, Hidroxymethylglutaryl-CoA-Reductase Inhibition, Síndrome Coronariana Aguda, 03 medical and health sciences, 0302 clinical medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Infarto do Miocárdio, Acute Coronary Syndrome, Retrospective Studies, Gynecology, business.industry, Incidence, Artigo Original, Follow up studies, Statins, RC666-701, Hyperglycemia, Original Article, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Glicemia, Estatinas, Follow-Up Studies
Abstract

Resumo Fundamento O maior risco de se desenvolver diabetes com o uso de estatinas é um desafio para a segurança do uso dessa classe de medicamentos em longo prazo. No entanto, poucos estudos analisaram essa questão durante síndromes coronarianas agudas (SCA). Objetivos Investigar a associação entre início precoce da terapia com estatina e níveis de glicemia em pacientes admitidos com SCA. Métodos Este foi um estudo retrospectivo de pacientes hospitalizados por SCA. Pacientes que nunca haviam usado estatinas foram incluídos e divididos segundo uso ou não de estatina nas primeiras 24 horas de internação. O desfecho primário foi a incidência de hiperglicemia na internação (definida como pico de glicemia > 200mg/dL). Modelos de regressão logística e modelos lineares multivariados foram usados para ajuste quanto a fatores de confusão e um modelo de pareamento por escore de propensão foi desenvolvido para comparações entre os dois grupos de interesses. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. Resultados Um total de 2357 pacientes foram incluídos, 1704 deles alocados no grupo que receberam estatinas e 653 no grupo que não receberam estatinas nas primeiras 24 horas de internação. Após os ajustes, uso de estatina nas primeiras 24 horas foi associado com uma menor incidência de hiperglicemia durante a internação (OR ajustado = 0,61, IC95% 0,46-0,80; p < 0,001) e menor necessidade de uso de insulina (OR ajustado = 0,56, IC 95% 0,41-0,76; p < 0,001). Essas associações mantiveram-se similares nos modelos de pareamento por escore de propensão, bem como após análises de sensibilidade, como exclusão de pacientes que desenvolveram choque cardiogênico, infecção grave ou pacientes que foram a óbito durante a internação hospitalar. Conclusões Entre os pacientes internados com SCA que não receberam estatinas previamente, a terapia precoce com estatina associou-se independentemente com menor incidência de hiperglicemia durante a internação. (Arq Bras Cardiol. 2021; 116(2):285-294) Abstract Background Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS). Objective To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS. Methods This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant. Results A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization. Conclusions Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294)

Published
2021

31. Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Author

Lars Wallentin, Claes Held, Paul W. Armstrong, Christopher P. Cannon, Richard Y. Davies, Christopher B. Granger, Emil Hagström, Robert A. Harrington, Judith S. Hochman, Wolfgang Koenig, Sue Krug‐Gourley, Emile R. Mohler, Agneta Siegbahn, Elizabeth Tarka, Philippe Gabriel Steg, Ralph A. H. Stewart, Robert Weiss, Ollie Östlund, Harvey D. White, Andrzej Budaj, Diego Ardissino, Alvaro Avezum, Philip E. Aylward, Alfonso Bryce, Hong Chen, Ming‐Fong Chen, Ramon Corbalan, Anthony J. Dalby, Nicolas Danchin, Robbert J. De Winter, Stefan Denchev, Rafael Diaz, Moses Elisaf, Marcus D. Flather, Assen R. Goudev, Liliana Grinfeld, Steen Husted, Hyo‐Soo Kim, Ales Linhart, Eva Lonn, José López‐Sendón, Athanasios J. Manolis, José C. Nicolau, Prem Pais, Alexander Parkhomenko, Terje R. Pedersen, Daniel Pella, Marco A. Ramos‐Corrales, Mikhail Ruda, Mátyás Sereg, Saulat Siddique, Peter Sinnaeve, Piyamitr Sritara, Henk P. Swart, Rody G. Sy, Tamio Teramoto, Hung‐Fat Tse, W. Douglas Weaver, Margus Viigimaa, Dragos Vinereanu, and Junren Zhu

Subjects
atherosclerosis, coronary disease, inflammation, lipoprotein, myocardial infarction, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundWe evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and ResultsPlasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. ConclusionsAlthough high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

Published
2016
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32. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure

Author

Stefano Savonitto, D Soon, V Tseluyko, J Heymeriks, L Petrescu, Fabio T. M. Costa, P Garcia Pacho, G Chapidze, Michael Motro, M Diez, A Prado, Piotr Ponikowski, Sanjib Kumar Sharma, DL Serban, A. Salvioni, S del Prado, Giuseppe Boriani, Stephan von Haehling, HG Cestari, PR Nierop, LC Iosipescu, Hans Kragten, Má Hominal, Bridget-Anne Kirwan, Andre Keren, D Horvat, J Thierer, D Sim, Rabih R. Azar, Peter van der Meer, G Stanciulescu, F Cosmi, Sy Loh, Jarosław Drożdż, David Sim, K Paposhvili, M Berli, Alain Cohen-Solal, Stefan D. Anker, Arnaout, ML Parody, GO Zapata, T Ben-Gal, J Schaap, Bas L.J.H. Kietselaer, O Raed, G Kiwan, Marco Metra, Shaul Atar, Udo Michael Göhring, Edoardo Gronda, A Ružić, C Beltrano, Dpw Beelen, Davor Milicic, R Ray, JM Weinstein, FI Ga Bosa Ojeda, Y-K Wong, Dalton Bertolim Précoma, Javed Butler, JR Gonzalez Juanatey, V Chumburidze, Gerasimos Filippatos, V Witzling, Y Malynovsky, I Kraiz, A Samodol, J Trevelyan, L Nigro Maia, M Stanislavchuk, Gilmar Reis, I Khintibidze, D Zdrenghea, Beata Wożakowska-Kapłon, BD Molina, C Abdallah, Ham van Kesteren, Tim Friede, Marcin Gruchała, Majdi Halabi, Ewa A. Jankowska, P Van Bergen, Constantin Militaru, O Koval, DA Darabantiu, A Kormann, J Szachniewicz, Maria Dorobantu, M van de Wetering, R Nijmeijer, H Hamdan, Stefano Ghio, Henry J. Dargie, G Azize, Nicolas Danchin, S Chaaban, S Gerward, P Pimentel Filho, M Uguccioni, K Abdelbaki, N Vita, J.F.K. Saraiva, D Almeida, Michael Shochat, M Ohlsson, R Van de Wal, V Zolotaikina, W Kinany, A Tycińska, A Hershson, T Shaburishvili, Vincent Fabien, FR dos Santos, Alfredo Bardají, Rgej Groutars, M Flugelman, J Bono, M Udovicic, M Artuković, K Šutalo, J Drozdz, TJ Yeo, F Ferre Pacora, Z Lominadze, M Emans, S Pettit, HA Luquez, P Terrosu, Marcus Ohlsson, M Gąsior, S Tušek, Enrico Passamonti, Nyy Al-Windy, P Midi, DA Pascual Figal, P van der Meer, V Zvi, Wilco Tanis, Felipe Martinez, RR Borelli, Diana A. Gorog, O Parhomenko, Klaus H Jensen, M Meijs, J Nessler, M Piepoli, DM Toader, Jose C. Nicolau, A Glenny, José Luis Zamorano, L Tilling, T McDonagh, K Pesek, H Fernandez, Davor Miličić, Domingo A. Pascual-Figal, Theresa McDonagh, G Khabeishvili, Josep Comin-Colet, Israel Gotsman, S Rassi, M Dorobantu, E Straburzyńska-Migaj, L Fattore, L Rudenko, D Crisu, S.S. Kabbani, M Gomez Bueno, Basil S. Lewis, S Goland, Y Arbel, M Bronisz, I Vakaliuk, A Fucili, A Mortara, R Zukermann, N Emukhvari, B Hassouna, K Mizia-Stec, F Turrini, R Szelemej, A Rodica Dan, L Lobo Marquez, Hadi Skouri, A Kabir, Frank Ruschitzka, R García Durán, R Gil, Michael Shechter, P Westendorp, Piergiuseppe Agostoni, A Fernandez, Oscar Pereira Dutra, P Ameri, Wolfram Doehner, JG Smith, Irakli Khintibidze, Luciano Moreira Baracioli, J Šikić, Stuart Pocock, Olivier C. Manintveld, MC Tomescu, M Di Biase, Luiz Carlos Bodanese, E Mirek-Bryniarska, Alexander Parkhomenko, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Cardiology, leboeuf, Christophe, Wrocław Medical University, London School of Hygiene and Tropical Medicine (LSHTM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], King's College Hospital (KCH), Universitatea din Bucuresti (UB), University of Lódź, Vifor Pharma Ltd [Glattbrugg, Switzerland], National and Kapodistrian University of Athens (NKUA), Hadassah Hebrew University Medical Center [Jerusalem], Tbilisi State University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Prague University of Economics and Business, Università degli Studi di Brescia = University of Brescia (UniBs), University of Zagreb, Universidade de São Paulo = University of São Paulo (USP), Skane University Hospital [Malmo], Lund University [Lund], National Scientific Center 'M.D. Strazhesko Institute of Cardiology' [Kyiv, Ukraine] (NSC/MDSIC), Universidad de Murcia, University hospital of Zurich [Zurich], National Heart Centre Singapore (NHCS), Saint Joseph Medical Center [Beirut], University Medical Center Groningen [Groningen] (UMCG), Clinical Cardiovascular Research Institute [Haifa, Israel] (2CRI), Bellvitge University Hospital [Barcelona, Spain], University Medical Center Göttingen (UMG), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Charité Campus Virchow-Klinikum (CVK), University of Glasgow, Tel Aviv University (TAU), University of Southern Mississippi (USM), Socar Research S.A. [Nyon, Switzerland] (SR), and AFFIRM-AHF investigators: G Azize, A Fernandez, G O Zapata, P Garcia Pacho, A Glenny, F Ferre Pacora, M L Parody, J Bono, C Beltrano, A Hershson, N Vita, H A Luquez, H G Cestari, H Fernandez, A Prado, M Berli, R García Durán, J Thierer, M Diez, L Lobo Marquez, R R Borelli, M Á Hominal, M Metra, P Ameri, P Agostoni, A Salvioni, L Fattore, E Gronda, S Ghio, F Turrini, M Uguccioni, M Di Biase, M Piepoli, S Savonitto, A Mortara, P Terrosu, A Fucili, G Boriani, P Midi, E Passamonti, F Cosmi, P van der Meer, P Van Bergen, M van de Wetering, Nyy Al-Windy, W Tanis, M Meijs, Rgej Groutars, Hks The, B Kietselaer, Ham van Kesteren, Dpw Beelen, J Heymeriks, R Van de Wal, J Schaap, M Emans, P Westendorp, P R Nierop, R Nijmeijer, O C Manintveld, M Dorobantu, D A Darabantiu, D Zdrenghea, D M Toader, L Petrescu, C Militaru, D Crisu, M C Tomescu, G Stanciulescu, A Rodica Dan, L C Iosipescu, D L Serban, J Drozdz, J Szachniewicz, M Bronisz, A Tycińska, B Wozakowska-Kaplon, E Mirek-Bryniarska, M Gruchała, J Nessler, E Straburzyńska-Migaj, K Mizia-Stec, R Szelemej, R Gil, M Gąsior, I Gotsman, M Halabi, M Shochat, M Shechter, V Witzling, R Zukermann, Y Arbel, M Flugelman, T Ben-Gal, V Zvi, W Kinany, J M Weinstein, S Atar, S Goland, D Milicic, D Horvat, S Tušek, M Udovicic, K Šutalo, A Samodol, K Pesek, M Artuković, A Ružić, J Šikić, T McDonagh, J Trevelyan, Y-K Wong, D Gorog, R Ray, S Pettit, S Sharma, A Kabir, H Hamdan, L Tilling, L Baracioli, L Nigro Maia, O Dutra, G Reis, P Pimentel Filho, J F Saraiva, A Kormann, F R Dos Santos, L Bodanese, D Almeida, D Precoma, S Rassi, F Costa, S Kabbani, K Abdelbaki, C Abdallah, M S Arnaout, R Azar, S Chaaban, O Raed, G Kiwan, B Hassouna, A Bardaji, J Zamorano, S Del Prado, J R Gonzalez Juanatey, F I Ga Bosa Ojeda, M Gomez Bueno, B D Molina, D A Pascual Figal, D Sim, T J Yeo, S Y Loh, D Soon, M Ohlsson, J G Smith, S Gerward, I Khintibidze, Z Lominadze, G Chapidze, N Emukhvari, G Khabeishvili, V Chumburidze, K Paposhvili, T Shaburishvili, G Khabeishvili, O Parhomenko, I Kraiz, O Koval, V Zolotaikina, Y Malynovsky, I Vakaliuk, L Rudenko, V Tseluyko, M Stanislavchuk.

Subjects
Male, medicine.medical_specialty, Anemia, 030204 cardiovascular system & hematology, Rate ratio, Placebo, Ferric Compounds, Ventricular Function, Left, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Maltose, Adverse effect, TOLVAPTAN, Aged, Aged, 80 and over, Heart Failure, RISK, Ejection fraction, Anemia, Iron-Deficiency, business.industry, MORTALITY, Hazard ratio, DEATH, General Medicine, Middle Aged, medicine.disease, Patient Discharge, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, Treatment Outcome, Heart failure, Administration, Intravenous, Female, HOSPITALIZATIONS, business
Abstract

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Published
2020
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33. Diabetes association with self‐reported health, resource utilization, and prognosis post‐myocardial infarction

Author

Carl Mellström, Stuart J. Pocock, Christopher B. Granger, Gunnar Brandrup-Wognsen, Ruth Owen, Jiyan Chen, Shaun G. Goodman, Jose C. Nicolau, Katarina Hedman, Richard Grieve, Remo H.M. Furtado, Dirk Westermann, Tabassome Simon, Mauricio G. Cohen, David Brieger, and Satoshi Yasuda

Subjects
Male, medicine.medical_specialty, Time Factors, Health Status, Population, Myocardial Infarction, Infarction, 030204 cardiovascular system & hematology, Coronary artery disease, cardiovascular events, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Risk Factors, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, education, Stroke, healthcare resource utilization, Aged, Creatinine, education.field_of_study, Quality and Outcomes, diabetes, business.industry, General Medicine, Prognosis, medicine.disease, quality of life, chemistry, Health Resources, Female, Self Report, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Background Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health‐related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post‐myocardial infarction (MI) patients with and without DM. Hypothesis In post‐MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes. Methods The prospective, observational long‐term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post‐MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and

Published
2020
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34. Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction A Prespecified Analysis of DAPA-HF

Author

Piotr Ponikowski, Akshay S. Desai, Mikaela Sjöstrand, David L. DeMets, Anna Maria Langkilde, Tereshchenko Sn, Mikhail Kosiborod, Subodh Verma, Lars Køber, Béla Merkely, John J.V. McMurray, Michael Böhm, Jose C. Nicolau, Inder S. Anand, Kieran F. Docherty, Tzvetana Katova, Per Johanson, Silvio E. Inzucchi, Felipe Martinez, Jonathan G. Howlett, Daniel Lindholm, Rudolf A. de Boer, Scott D. Solomon, Jarosław Drożdż, Eileen O'Meara, Marc S. Sabatine, Pardeep S. Jhund, Olof Bengtsson, and Cardiovascular Centre (CVC)

Subjects
medicine.medical_specialty, therapy, Ejection fraction, Adverse outcomes, business.industry, Treatment outcome, heart failure, medicine.disease, chemistry.chemical_compound, chemistry, Physiology (medical), Heart failure, Internal medicine, ENALAPRIL, medicine, Risk of mortality, Cardiology, sodium-glucose transporter 2 inhibitors, treatment outcome, Enalapril, Dapagliflozin, Cardiology and Cardiovascular Medicine, business, medicine.drug, hospitalization
Abstract

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events. Methods: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction ≤40% and elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide), were eligible. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or an urgent HF visit requiring intravenous therapy) or cardiovascular death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to the initiation of new, or the augmentation of existing, oral treatment. Results: Overall, 36% more patients experienced the expanded, in comparison with the primary, composite outcome. In the placebo group, 684 of 2371 (28.8%) patients and, in the dapagliflozin group, 527 of 2373 (22.2%) participants experienced the expanded outcome (hazard ratio, 0.73 [95% CI, 0.65–0.82]; P Conclusion: In DAPA-HF, outpatient episodes of HF worsening were common, were of prognostic importance, and were reduced by dapagliflozin. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03036124.

Published
2020
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35. Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease

Author

Shaun G. Goodman, Jose C. Nicolau, Andre Franci, Paulo Genestreti, Carlos J.D.G. Barbosa, Remo H.M. Furtado, Paul A. Gurbel, Talia Dalcoquio, Viviane Lima, Rocio Salsoso, Luciano Moreira Baracioli, Robert P. Giugliano, Raul C. Maranhão, and Celia Maria Cassaro Strunz

Subjects
Blood Platelets, 030213 general clinical medicine, medicine.medical_specialty, Platelet Function Tests, Population, Coronary Artery Disease, Gastroenterology, Coronary artery disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, P2Y12, Internal medicine, medicine, Clinical endpoint, Humans, Pharmacology (medical), Platelet, Lipoprotein (a), Risk factor, education, Original Research, education.field_of_study, Primary prevention, biology, business.industry, General Medicine, Lipoprotein(a), medicine.disease, Adenosine diphosphate, chemistry, 030220 oncology & carcinogenesis, biology.protein, Platelet reactivity, business, Platelet Aggregation Inhibitors
Abstract

Introduction Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Methods Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. Conclusion In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity. Electronic supplementary material The online version of this article (10.1007/s12325-020-01483-y) contains supplementary material, which is available to authorized users.

Published
2020
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37. Phase Ib dose-escalation study of the hypoxia-modifier myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors

Author

M Schneider, M Linecker, R Fritsch, U Mühlematter, D Stocker, B Pestalozzi, P Samaras, A Jetter, P Kron, H Petrowsky, C Nicolau, J-M Lehn, B Humar, R Graf, P-A Clavien, and P Limani

Subjects
Surgery
Abstract

Objective Hypoxia is present in most solid tumors and acts as a driver of malignancy. Myo-inositol trispyrophosphate (ITPP) is a novel re-oxygenating compound without apparent toxicity. In preclinical models, it potentiates the efficacy of subsequent chemotherapy through vascular normalization. We sought to assess the safety, tolerability, and preliminary efficacy of ITPP. Methods In this monocentric, open-label, dose-escalation study following a 3+3 design, eligible patients with advanced primary and secondary hepatopancreatobiliary tumors received nine 8-h infusions of ITPP during 3 weeks across eight dose levels (1866–14,500 mg/m2/dose), followed by standard chemotherapy. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics and estimation of efficacy based on radiological responses and angiogenic serum markers. Registration number: NCT02528526. Results From April 2015 to July 2018, a total of 28 enrolled patients were assessed for the primary endpoints. ITPP was safe up to single doses of 12,390 mg/m2, and 32 ITPP-related adverse events occurred: 19 (67.8%) hypercalcemia, 5 (17.8%) hyponatremia, and 4 (14.2%) hypomagnesemia. Following ITPP monotherapy, 52% of patients displayed morphological disease stabilization. Following subsequent chemotherapy, 10% showed a partial response, and 60% had stable disease. Angiogenic markers were decreased in 60% after ITPP and tended to correlate with responses and survival after chemotherapy. Conclusion Administration of ITPP is safe up to 12,390 mg/m2 with favorable pharmacokinetics. Preliminary translational efficacy data show decreased angiogenic markers, which might indicate an anti-hypoxic effect and enhancement of chemotherapy through ITPP.

Published
2022
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38. Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial

Author

Remo H.M. Furtado, Itamar Raz, Erica L. Goodrich, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Philip Aylward, Anthony J Dalby, Mikael Dellborg, Doina Dimulescu, José C. Nicolau, Anthonius J.M. Oude Ophuis, Avivit Cahn, Ofri Mosenzon, Ingrid Gause-Nilsson, Anna Maria Langkilde, Marc S. Sabatine, and Stephen D. Wiviott

Subjects
Heart Failure, Male, Myocardial Infarction, Blood Pressure, Acute Kidney Injury, Middle Aged, Diabetes Mellitus, Type 2, Glucosides, Physiology (medical), Humans, Female, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine, Sodium-Glucose Transporter 2 Inhibitors, Aged
Abstract

Background: Dapagliflozin improved heart failure and kidney outcomes in patients with type 2 diabetes (T2DM) with or at high risk for atherosclerotic cardiovascular disease in the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58). Here, the aim was to analyze the efficacy and safety of dapagliflozin stratified according to baseline systolic blood pressure (SBP). Methods: The DECLARE-TIMI 58 trial randomly assigned patients with T2DM and either previous atherosclerotic cardiovascular disease or atherosclerotic cardiovascular disease risk factors to dapagliflozin or placebo. Patients were categorized by baseline SBP levels: Results: The trial comprised 17 160 patients; mean age, 64.0±6.8 years; 37.4% women; median duration of T2DM, 11 years; 40.6% with prevalent cardiovascular disease. Overall, dapagliflozin reduced SBP by 2.4 mm Hg (95% CI, 1.9–2.9; P P interactions =0.28 and 0.52, respectively). Among normotensive patients, the hazard ratios were 0.66 (95% CI, 0.42–1.05) and 0.39 (95% CI, 0.19–0.78), respectively, for hospitalization for heart failure and the renal-specific outcome. Events of volume depletion, amputation, and acute kidney injury did not differ with dapagliflozin overall or within any baseline SBP group. Conclusions: In patients with T2DM with or at high atherosclerotic cardiovascular disease risk, dapagliflozin reduced risk for hospitalization for heart failure and renal outcomes regardless of baseline SBP, with no difference in adverse events of interest at any level of baseline SBP. These results indicate that dapagliflozin provides cardiorenal benefits in patients with T2DM at high atherosclerotic cardiovascular disease risk independent of baseline blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.

Published
2022

40. Abstract No. 9 ▪ FEATURED ABSTRACT Pivotal Study of Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation (TULSA) of the Prostate: 4-year Follow-up

Author

S. Raman, S. Arora, K. Macura, A. Oto, J. Futterer, R. Staruch, T. Tirkes, D. Bonekamp, M. Haider, D. Cool, K. Nandalur, C. Nicolau, D. Costa, T. Persigehl, G. Clarke, J. Chin, L. Klotz, and S. Eggener

Subjects
Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Published
2023
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42. The role of invasive therapies in elderly patients with acute myocardial infarction

Author

José C. Nicolau, Pedro A. Lemos, Maurício Wajngarten, Roberto R. Giraldez, Carlos V. Serrano Jr., Eulógio E. Martinez, Luciano M. Baracioli, Roberto Kalil, Fábio B. Jatene, Luis A. Dallan, Luis B. Puig, and Noedir A. Stolf

Subjects
Myocardial infarction, Long-term outcome, Elderly population, Coronary artery bypass surgery, Percutaneous coronary intervention, Medicine (General), R5-920
Abstract

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies - IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were >70 years old (elderly group - EG), and 1040 were

Published
2009
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43. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author

Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. 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Timothy Reynolds, David Sharman, david Spriging, Rob Butler, Peter Wilkinson, Gregory YH Lip, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D’Urso, Fadi El- Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. 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G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. P., Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Wilson, Matthew D., Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Tze-Kay Yan, Andrew, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Schiavi, Lilia B., Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Christenson, Stuart, Dotani, Imran, Garrido, Marcelo, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Alvarisqueta, Andrés F., Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Sassone, Sonia A., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Bordonava, Anselmo P., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Alves De Lima, Alberto E., Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Schmidberg, Jorge M., Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E., Butters, Julie, Griffith, Liddy, Duronto, Ernesto A., Shaw, Michelle, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Caruso, Orlando C., Tamby, Jean-Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Novaretto, Leonardo P., Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Hominal, Miguel Angel, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Montaña, Oscar R., Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Caccavo, Alberto, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Gomez Vilamajo, Oscar A., Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Lorenzatti, Alberto J., Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., McClanahan, Mark A., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio Oe, Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Schwartz, Gregory G., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo Ds, Colombo, Hugo R., Bhatt, Deepak L., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Bittner, Vera A., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris Ls, Shaw, James, Diaz, Rafael, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven Gm, Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Harrington, Robert A., Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Jukema, J. Wouter, Vrolix, Mathias Cm, De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Dilic, Mirza, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Zeiher, Andreas M., Rech, Rafael, Rossi, Paulo Rf, Cerqueira, Maria José Ag, Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler On, Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Manenti, Euler Roberto F. Fernandes, Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Neto, Jose A. Marin, Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar Ksb, Reis, Helder Jl, Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Edelberg, Jay M., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Gotcheva, Nina N., Ivanova, Raya, Gospodinov, Maryana, Hanotin, Corinne, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, Moryusef, Angèle, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Pordy, Robert, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Sasiela, William J., Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Tamby, Jean-François, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, De Salazar, Dora I. Molina, Bonfanti, Alberto J. Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Prieto, Juan-Carlos, Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Trujillo, Angela M. Fernandez, Yong, Huo, Strozzi, Maja, Car, Siniša, Miličić, Davor, Lovrić Benčić, Martina, Pintarić, Hrvoje, Prvulović, Đeiti, Šikić, Jozica, Peršić, Viktor, Mileta, Dean, Štambuk, Kresimir, López-Jaramillo, Patricio, Babić, Zdravko, Tomulic, Vjekoslav, Lukenda, Josip, Mejic-Krstulovic, Stanka, Starcevic, Boris, Spinar, Jindrich, Horak, David, Velicka, Zdenek, Alan, David, Machova, Vilma, Pećin, Ivan, Linhart, Ales, Novotny, Vojtech, Kaucak, Vladimir, Rokyta, Richard, Naplava, Robert, Coufal, Zdenek, Adamkova, Vera, Podpera, Ivo, Zizka, Jiri, Motovska, Zuzana, Reiner, Zeljko, Marusincova, Ivana, Ostadal, Petr, Heinc, Petr, Kuchar, Jiri, Povolny, Petr, Matuska, Jiri, Poulsen, Steen H., Raungaard, Bent, Clemmensen, Peter, Bang, Lia E., May, Ole, Bøttcher, Morten, Hove, Jens D., Frost, Lars, Gislason, Gunnar, Larsen, John, Johansen, Peter Betton, Hald, Flemming, Johansen, Peter, Jeppesen, Jørgen, Poulsen, Steen Hvitfeldt, Nielsen, Tonny, Kristensen, Kjeld S., Walichiewicz, Piotr Maria, Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S., Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Chumburidze, Vakhtang, Lefèvre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Marx, Nikolaus, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Liberopoulos, Evangelos, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Carlos, Pablo, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Valdovinos, Montenegro, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Tse, Hung-Fat, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Kiss, Robert Gabor, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, Apostolos, Fausto Ovando, Sergio R., Montenegro Valdovinos, Pablo Carlos, Arango Benecke, Juan L., Xavier, Denis, Rodriguez De Leon, Edgar R., Yan, Bryan Py, Siu, David Cw, Turi, Tibor, Merkely, Bela, Gabor Kiss, Robert, Ungi, Imre, Lupkovics, Geza, Nagy, Lajos, Katona, András, Zahger, Doron, Édes, István, Müller, Gábor, Horvath, Iván, Kapin, Tibor, Szigeti, Zsolt, Faluközy, József, Kumbla, Mukund, Sandhu, Manjinder, Annam, Sharath, Reddy Proddutur, Naveen, Valgimigli, Marco, Regella, Reddy, Premchand, Rajendra K., Mahajan, Ajaykumar, Pawar, Sudhir, Abhyanakar, Atul D., Kerkar, Prafulla, Govinda, Ravishankar A., Oomman, Abraham, Sinha, Dhurjati, Patil, Sachin N., Kimura, Takeshi, Kahali, Dhiman, Sawhney, Jitendra, Joshi, Abhijeet B., Chaudhary, Sanjeev, Harkut, Pankaj, Guha, Santanu, Porwal, Sanjay, Jujjuru, Srimannarayana, Pothineni, Ramesh B., Monteiro, Minguel R., Kim, Hyo Soo, Khan, Aziz, Iyengar, Shamanna S., Grewal, Jasprakash Singh, Chopda, Manoj, Fulwani, Mahesh C., Patange, Dr 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Gavish, Dov, Ramos López, Gabriel Arturo, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Garbelotto, Raffaella, Alings, Marco, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B., Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, PierMarco, Palvarini, Michela, Halvorsen, Sigrun, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Correa Flores, Roger M., Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Sy, Rody G., Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Budaj, Andrzej, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Yoon, Jung Han, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Chua, 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Rolando J., Hernandez Zuniga, Jose D., Camacho Cosavalente, Luis A., Bravo Mannucci, Jorge E., Landeo, Javier Heredia, Llerena Navarro, Nassip C., Roldan Concha, Yudy M., Rodriguez Chavez, Víctor E., Anchante Hernandez, Henry A., Zea Nunez, Carlos A., Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Ray, Kausik K., Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Bhatt, Deepak L, Bittner, Vera A, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A

Subjects
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract

Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]

Published
2022
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44. Abstract 10724: Long-Term Mortality After Acute Coronary Syndromes Among Patients with Normal, Mid-Range or Low Ejection Fraction

Author

Remo Furtado, Marcela G Juliasz, FELIPE Y CHIU, Livia B Bastos, Talia F Dalcoquio, Felipe G Lima, Renato Rosa, Cesar A Caporrino, Adriadne Bertolin, Carla Soffiatti, Andre S Ribeiro, Maria C Andrade, Roberto Giraldez, Luciano Baracioli, and Jose C Nicolau

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Left ventricle ejection fraction (LVEF) is a well-established marker for survival after acute coronary syndromes (ACS). While there has been strong association between low ejection fraction (i.e., LVEF < 40%) and mortality, the long-term prognostic impact of mid-range EF (LVEF 40-49%) after ACS remains less clear. Methods: This was a retrospective study enrolling consecutive patients admitted with ACS included in a single tertiary center databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mid-range (40-49%) and low (< 40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox regression model was used to adjust for confounders. The model was adjusted for age, sex, race, history of diabetes mellitus, prior HF, arterial hypertension, dyslipidemia, smoking, STEMI versus non-ST elevation ACS, prior MI, prior PCI, prior CABG, creatinine and Killip class at admission Results: A total of 3200 patients were included (1,952 with normal EF; 659 with mid-range EF and 589 with low EF); mean age was 63.5 ± 12.4 years (63.2±12.3, 63.9±12.7 and 64.2±12.4 years, respectively for normal, mid-range and low EF; p = 0.14); 2216 (69.3%) were male and 1257 (39.3%) presented with STEMI. The median follow-up time was 5 years, and the maximum follow-up time was 17.8 years. Overall results are shown in the Figure 1. In a sensitivity analysis using a different definition for mid-range EF (36-54%), results remained similar (data not shown). Conclusion: In ACS patients discharged alive from hospital, mid-range EF measured in the acute phase was associated with increased long-term mortality compared to patients with normal EF. This magnitude of effect was similar to that observed for patients with low EF. These data reinforce the need to consider anti-remodeling therapies also for ACS patients who have LVEF in the mid-range.

Published
2021
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45. Endovascular Therapeutic Hypothermia Adjunctive To Percutaneous Coronary Intervention in Acute Myocardial Infarction: Realistic Simulation as a Game Changer

Author

Sergio Timerman, Luis Alberto Oliveira Dallan, Roberto Kalil Filho, Luis Augusto Palma Dallan, Natali Schiavo Giannetti, Mucio Tavares de Oliveira, Expedito Eustáquio Ribeiro da Silva, Michael Dae, Carlos Eduardo Rochitte, Claudia Yanet Bernoche San Martin, Tathiane Facholi Polastri, Pedro Alves Lemos Neto, Ludhmila Abrahão Hajjar, Felipe Gallego Lima, Marian Keiko Frossard Lima, and Jose C. Nicolau

Subjects
medicine.medical_specialty, business.industry, Internal medicine, medicine.medical_treatment, medicine, Cardiology, Percutaneous coronary intervention, cardiovascular diseases, Myocardial infarction, Hypothermia, medicine.symptom, business, medicine.disease
Abstract

Background: Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI. Methods and Results: We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System. The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Conclusions: Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI. ClinicalTrials.gov: NCT02664194.

Published
2021
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46. HDL proteome remodeling associates with COVID-19 severity

Author

Gabrielly Alexandria, Carsten Wrenger, Claudio Romero Farias Marinho, Amanda Ribeiro Martins da Silva, Giuseppe Palmisano, Santhosh D. Bhosale, Talia Dalcoquio, Fabio de Rose Ghilardi, Livia Rosa-Fernandes, Adriadne Justi Bertolin, Paolo Di Mascio, Douglas Ricardo de Souza Junior, Jose C. Nicolau, Graziella E. Ronsein, Rinaldo Focaccia Siciliano, Lorenna Rocha Reis, and Martin R. Larsen

Subjects
Adult, Male, Proteomics, medicine.medical_specialty, Apolipoprotein B, HDL, Endocrinology, Diabetes and Metabolism, Disease, APOF, Gastroenterology, Mass Spectrometry, Article, Internal medicine, Internal Medicine, Quantitative proteomics, Medicine, Humans, Serum amyloid A, Triglycerides, Serum Amyloid A Protein, Nutrition and Dietetics, biology, business.industry, Cholesterol, HDL, COVID-19, Odds ratio, Middle Aged, APOM, Apolipoproteins, GORDURAS, Proteome, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, Lipoproteins, HDL, Infection, Lipoprotein
Abstract

Background: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. Objective: We used a quantitative proteome approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). Methods: Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. Results: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007). Conclusion: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.

Published
2021
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47. Determinants of long-term dual antiplatelet therapy use in post myocardial infarction patients: Insights from the TIGRIS registry

Author

Gunnar Brandrup-Wognsen, Akshay Bagai, Andrew T. Yan, Shaun G. Goodman, Christopher B. Granger, Mauricio G. Cohen, David Brieger, Karolina Andersson Sundell, Stuart J. Pocock, Juan J Russo, Dirk Westermann, Jose C. Nicolau, Ruth Owen, Tabassome Simon, and Satoshi Yasuda

Subjects
medicine.medical_specialty, animal structures, Time Factors, medicine.medical_treatment, Myocardial Infarction, Infarction, Angina, Percutaneous Coronary Intervention, Diabetes mellitus, Internal medicine, medicine, Humans, Myocardial infarction, Prospective Studies, Registries, Aged, business.industry, Percutaneous coronary intervention, medicine.disease, Discontinuation, Treatment Outcome, Heart failure, Cohort, Cardiology, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors
Abstract

BACKGROUND Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. METHODS TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. RESULTS Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients

Published
2021

48. Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction

Author

Olof Bengtsson, Mikhail Kosiborod, Jose C. Nicolau, Marc S. Sabatine, Kieran F. Docherty, Lars Køber, Felipe Martinez, Pardeep S. Jhund, Béla Merkely, Mirta Diez, Piotr Ponikowski, Mark C. Petrie, Daniel Lindholm, Silvio E. Inzucchi, David L. DeMets, Anna Maria Langkilde, John J.V. McMurray, Mikaela Sjöstrand, Subodh Verma, Masafumi Kitakaze, Anna Niklasson, and Scott D. Solomon

Subjects
Male, medicine.medical_specialty, MEDLINE, heart failure, health status, Physical function, Glucosides/pharmacology, chemistry.chemical_compound, Quality of life, Physiology (medical), Internal medicine, Odds Ratio, sodium-glucose transporter 2 inhibitors, Humans, Medicine, Ventricular Function, Left/drug effects, In patient, Prospective Studies, Dapagliflozin, Aged, Hospitalization/statistics & numerical data, Proportional Hazards Models, Ejection fraction, business.industry, Middle Aged, Heart Failure/drug therapy, Placebo Effect, medicine.disease, Survival Analysis, Benzhydryl Compounds/pharmacology, Treatment Outcome, chemistry, Heart failure, Quality of Life, outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Goals of management in patients with heart failure and reduced ejection fraction include reducing death and hospitalizations, and improving health status (symptoms, physical function, and quality of life). In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), sodium–glucose cotransporter-2 inhibitor, dapagliflozin, reduced death and hospitalizations, and improved symptoms in patients with heart failure and reduced ejection fraction. In this analysis, we examine the effects of dapagliflozin on a broad range of health status outcomes, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: KCCQ was evaluated at randomization, 4 and 8 months. Patients were divided by baseline KCCQ total symptom score (TSS); Cox proportional hazards models examined the effects of dapagliflozin on clinical events across these subgroups. We also evaluated the effects of dapagliflozin on KCCQ-TSS, clinical summary score, and overall summary score. Responder analyses were performed to compare proportions of dapagliflozin versus placebo-treated patients with clinically meaningful changes in KCCQ at 8 months. Results: A total of 4443 patients had available KCCQ at baseline (median KCCQ-TSS, 77.1 [interquartile range, 58.3–91.7]). The effects of dapagliflozin vs placebo on reducing cardiovascular death or worsening heart failure were consistent across the range of KCCQ-TSS (lowest to highest tertile: hazard ratio, 0.70 [95% CI, 0.57–0.86]; hazard ratio, 0.77 [95% CI, 0.61–0.98]; hazard ratio, 0.62 [95% CI, 0.46–0.83]; P for heterogeneity=0.52). Patients treated with dapagliflozin had greater improvement in mean KCCQ-TSS, clinical summary score, and overall summary score at 8 months (2.8, 2.5 and 2.3 points higher versus placebo; P P P Conclusions: Dapagliflozin reduced cardiovascular death and worsening heart failure across the range of baseline KCCQ, and improved symptoms, physical function, and quality of life in patients with heart failure and reduced ejection fraction. Furthermore, dapagliflozin increased the proportion of patients experiencing at least small, moderate, and large improvements in health status; these effects were clinically important. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03036124.

Published
2020
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49. Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography

Author

Marc S. Sabatine, Remo H.M. Furtado, Jianping Guo, L. Kristin Newby, KyungAh Im, Jose C. Nicolau, Jennifer A. White, and Robert P. Giugliano

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, 030204 cardiovascular system & hematology, Coronary Angiography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, ST segment, 030212 general & internal medicine, Myocardial infarction, Acute Coronary Syndrome, Non-ST Elevated Myocardial Infarction, Aged, Morphine, business.industry, Hazard ratio, Odds ratio, Middle Aged, Clopidogrel, medicine.disease, Analgesics, Opioid, Treatment Outcome, Concomitant, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Background Mechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial. Objectives This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls. Methods Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days. Results In patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; pinteraction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; pinteraction = 0.46). Conclusions When used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895 )

Published
2020
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50. Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54

Author

KyungAh Im, P. Gabriel Steg, Remo H.M. Furtado, Eugene Braunwald, Róbert Gábor Kiss, Ramón Corbalán, Andrzej Budaj, Eva C. Jensen, Frederic Kontny, Robert F. Storey, Giulia Magnani, Maria Teresa B. Abola, Jindrich Spinar, Jose C. Nicolau, Per Johanson, Deepak L. Bhatt, Marc P. Bonaca, and Marc S. Sabatine

Subjects
Relative risk reduction, Ticagrelor, medicine.medical_specialty, Adenosine, Myocardial Infarction, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Secondary Prevention, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Stroke, Aspirin, business.industry, Hazard ratio, medicine.disease, Treatment Outcome, Purinergic P2Y Receptor Antagonists, Cardiology, Drug Therapy, Combination, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, Mace, TIMI, medicine.drug
Abstract

Aims PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. Methods and results This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1–3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15–1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68–0.99) and with prior stenting (HR 0.85, 95% CI 0.75–0.96; P for interaction = 0.76). Conclusion Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. ClinicalTrials.gov Identifier NCT01225562.

Published
2019
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