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Article: Enhancing Arrhythmogenic Right Ventricular Cardiomyopathy Detection and Risk Stratification: Insights from Advanced Echocardiographic Techniques.

Olivetti, Natália / Sacilotto, Luciana / Moleta, Danilo Bora / França, Lucas Arraes de / Capeline, Lorena Squassante / Wulkan, Fanny / Wu, Tan Chen / Pessente, Gabriele D'Arezzo / Carvalho, Mariana Lombardi Peres de / Hachul, Denise Tessariol / Pereira, Alexandre da Costa / Krieger, José E / Scanavacca, Mauricio Ibrahim / Vieira, Marcelo Luiz Campos / Darrieux, Francisco

Diagnostics (Basel, Switzerland)

2024 Volume 14, Issue 2

Abstract: Introduction: The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has ...

Abstract	Introduction: The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes. Methods: The study included 28 patients from the Heart Institute of São Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR. Results: In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd ( Conclusion: Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers.
Language	English
Publishing date	2024-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics14020150
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Article ; Online: Evaluation of a new treadmill exercise protocol to unmask type 1 Brugada electrocardiographic pattern: can we improve diagnostic yield?

Pichara, Nemer L / Sacilotto, Luciana / Scanavacca, Maurício I / Cardoso, Acácio Fernandes / Soares, Beatriz Moreira Ayub Ferreira / Falcochio, Paola P Pn F / Falcão, Andrea M G / Olivetti, Natalia / da Costa Darrieux, Francisco Carlos / Chalela, William A

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

2023 Volume 25, Issue 7

Abstract: Aims: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing ( ... ...

Abstract	Aims: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG. Methods and results: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone. Conclusion: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.
MeSH term(s)	Humans ; Male ; Female ; Exercise Test ; China ; Brugada Syndrome/diagnosis ; Electrocardiography/methods ; Brazil
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1449879-0
ISSN	1532-2092 ; 1099-5129
ISSN (online)	1532-2092
ISSN	1099-5129
DOI	10.1093/europace/euad157
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Article ; Online: Family Screening in the Diagnosis of Short QT Syndrome after Sudden Cardiac Death as First Manifestation in Young Siblings.

Athayde, Guilherme Augusto Teodoro / Olivetti, Natália Quintella Sangiorgi / Darrieux, Francisco Carlos da Costa / Sacilotto, Luciana / Pessente, Gabrielle D'Arezzo / Scanavacca, Maurício Ibrahim

Arquivos brasileiros de cardiologia

2021 Volume 117, Issue 1 suppl 1, Page(s) 12–15

Title translation	Triagem Familiar no Diagnóstico da Síndrome do QT Curto após Morte Súbita Cardíaca como Primeira Manifestação em Jovens Irmãos.
MeSH term(s)	Arrhythmias, Cardiac/diagnosis ; Death, Sudden, Cardiac/etiology ; Electrocardiography ; Humans ; Siblings
Language	Portuguese
Publishing date	2021-07-21
Publishing country	Brazil
Document type	Case Reports
ZDB-ID	730261-7
ISSN	1678-4170 ; 0066-782X
ISSN (online)	1678-4170
ISSN	0066-782X
DOI	10.36660/abc.20200274
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Zs.A 548: Show issues

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Article ; Online: ETS factors are required but not sufficient for specific patterns of enhancer activity in different endothelial subtypes.

Neal, Alice / Nornes, Svanhild / Louphrasitthiphol, Pakavarin / Sacilotto, Natalia / Preston, Mark D / Fleisinger, Lucija / Payne, Sophie / De Val, Sarah

Developmental biology

2021 Volume 473, Page(s) 1–14

Abstract: Correct vascular differentiation requires distinct patterns of gene expression in different subtypes of endothelial cells. Members of the ETS transcription factor family are essential for the transcriptional activation of arterial and angiogenesis- ... ...

Abstract	Correct vascular differentiation requires distinct patterns of gene expression in different subtypes of endothelial cells. Members of the ETS transcription factor family are essential for the transcriptional activation of arterial and angiogenesis-specific gene regulatory elements, leading to the hypothesis that they play lineage-defining roles in arterial and angiogenic differentiation directly downstream of VEGFA signalling. However, an alternative explanation is that ETS binding at enhancers and promoters is a general requirement for activation of many endothelial genes regardless of expression pattern, with subtype-specificity provided by additional factors. Here we use analysis of Ephb4 and Coup-TFII (Nr2f2) vein-specific enhancers to demonstrate that ETS factors are equally essential for vein, arterial and angiogenic-specific enhancer activity patterns. Further, we show that ETS factor binding at these vein-specific enhancers is enriched by VEGFA signalling, similar to that seen at arterial and angiogenic enhancers. However, while arterial and angiogenic enhancers can be activated by VEGFA in vivo, the Ephb4 and Coup-TFII venous enhancers are not, suggesting that the specificity of VEGFA-induced arterial and angiogenic enhancer activity occurs via non-ETS transcription factors. These results support a model in which ETS factors are not the primary regulators of specific patterns of gene expression in different endothelial subtypes.
Language	English
Publishing date	2021-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2021.01.002
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Article ; Online: Impact of adherence to warfarin therapy during 12 weeks of pharmaceutical care in patients with poor time in the therapeutic range.

Marcatto, Leiliane / Boer, Bruno / Sacilotto, Luciana / Olivetti, Natália / Darrieux, Francisco Carlos Costa / Scanavacca, Maurício Ibrahim / Pereira, Alexandre Costa / Santos, Paulo Caleb Junior Lima

Journal of thrombosis and thrombolysis

2020 Volume 51, Issue 4, Page(s) 1043–1049

Abstract: Poor adherence to warfarin treatment is a contributor to poor quality of treatment, which increases the risk of bleeding and thromboembolic events. This study aims to evaluate the impact of adherence to warfarin therapy on anticoagulation quality during ... ...

Abstract	Poor adherence to warfarin treatment is a contributor to poor quality of treatment, which increases the risk of bleeding and thromboembolic events. This study aims to evaluate the impact of adherence to warfarin therapy on anticoagulation quality during 12 weeks of pharmaceutical care and after 1 year of follow-up for patients with atrial fibrillation and with poor TTR. The Arrhythmia Unit of tertiary hospital in Brazil. We included 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR < 50%). Pharmacist-driven therapy management was performed for 12 weeks and patients were also evaluated 1 year after the end of the follow-up with a pharmacist. Adherence was classified into high adherence, medium adherence and low adherence. Impact of adherence to warfarin therapy after pharmaceutical care. Of the 262 patients, 160 were high adherence, 71 were medium adherence and 31 were low adherence. No statistically significant difference is found between adherence groups in demographic and clinical variables. The TTR basal means were not different among adherence groups (p = 0.386). However, the means of TTR 12 weeks and TTR 1 year after the end of protocol were statistically different among adherence groups (p < 0.001 and p = 0.002, respectively). When we compared TTR values at different times within the adherence group, we observed that there is a statistical difference between the three TTR means (basal versus 12 weeks versus 1 year after) within the adherence group (p < 0.001). Patients with poor anticoagulation control, who adhered to the treatment with warfarin during the pharmaceutical care had better anticoagulation quality compared to those who did not adhere to the therapy with warfarin.
MeSH term(s)	Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; Blood Coagulation/drug effects ; Humans ; International Normalized Ratio ; Pharmaceutical Services ; Treatment Outcome ; Warfarin/pharmacology ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2020-09-24
Publishing country	Netherlands
Document type	Letter
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-020-02280-8
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Zs.A 4352: Show issues

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Article: Effect of Occurrence of Lamin A/C (

Pessente, Gabrielle D'Arezzo / Sacilotto, Luciana / Calil, Zaine Oliveira / Olivetti, Natalia Quintella Sangiorgi / Wulkan, Fanny / de Oliveira, Théo Gremen Mimary / Pedrosa, Anísio Alexandre Andrade / Wu, Tan Chen / Hachul, Denise Tessariol / Scanavacca, Maurício Ibrahim / Krieger, José Eduardo / Darrieux, Francisco Carlos da Costa / Pereira, Alexandre da Costa

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 823717

Abstract: Objective: Mutations in the : Methods: One-hundred and one consecutive patients with "lone AF" criteria were initially screened by genetic testing. Genetic variants were classified according to the American College of Genetic and Genomic criteria. ... ...

Abstract	Objective: Mutations in the Methods: One-hundred and one consecutive patients with "lone AF" criteria were initially screened by genetic testing. Genetic variants were classified according to the American College of Genetic and Genomic criteria. All subjects were evaluated through clinical and familial history, ECG, 24-h Holter monitoring, echocardiogram, cardiac magnetic resonance, treatment response, and the present relatives of Results: Three missense variants in Conclusion: Although a rare occurrence, our findings emphasize the possibility of an initial presentation of apparently "lone AF" in
Language	English
Publishing date	2022-04-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.823717
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Article ; Online: Left Atrial Thrombus and Dense Spontaneous Contrast in Direct Oral Anticoagulant Therapy of Atrial Fibrillation: Insights from a Reference Center.

Marques, Thiago / Darrieux, Francisco / Gouvêa, Fábio / Garambone, Leandro / Lindoso, Ana Paula / Lage, João / Sacilotto, Luciana / Coimbra, Ana Lúcia / Pinheiro, Martina / Olivetti, Natália / Lara, Sissy / Hardy, Carina / Athayde, Guilherme / Hachul, Denise / Pisani, Cristiano / Wu, Tan Chen / Scanavacca, Maurício

Arquivos brasileiros de cardiologia

2022 Volume 119, Issue 4, Page(s) 514–519

Abstract: Background: In the treatment of atrial fibrillation (AF), the most frequently sustained arrhythmia, with catheter ablation (CA) or electrical cardioversion (ECV), the periprocedural period is one of the most critical phases. Currently, the use of new ... ...

Title translation	Trombo Atrial Esquerdo e Contraste Espontâneo Denso no Uso de Anticoagulante Oral de Ação Direta em Fibrilação Atrial: Visão de Centro Referenciado.
Abstract	Background: In the treatment of atrial fibrillation (AF), the most frequently sustained arrhythmia, with catheter ablation (CA) or electrical cardioversion (ECV), the periprocedural period is one of the most critical phases. Currently, the use of new direct action oral anticoagulants (DOAC) is increasingly frequent; however, in the real world, there are still few data on studies on the thrombus incidence in the left atrium (TrLA) or dense spontaneous contrast (DSC) on transesophageal echocardiogram (TEE). Objective: To evaluate the prevalence of events and association with risk factors in patients using DOACs. Primary objective: to analyze the prevalence of thrombus in the LA by TEE in patients using DOAC undergoing ECV/CA. Second, evaluate the association of comorbidities with the presence of thrombi and DSC. Methods: Retrospective cohort, single-center study with patients followed at the Arrhythmia Outpatient Unit (InCor-HCFMUSP). Patients indicated for procedures and using DOACs were selected, and their clinical/echocardiographic data were analyzed. A significance level of 5% was considered. Results: 354 patients were included, a total of 400 procedures, from March 2012-March 2018. Thrombus in the LA was found in 11 patients (2.8%), associated with advanced age (p=0.007) and higher CHA2DS2-VASc (p<0.001) score. DSC in the LA before TEE was found in 29 patients (7.3%), with lower LVEF (p<0.038) and greater LA dimension (p<0.0001). Conclusion: The incidence of LA thrombus and DSC in patients using DOC in the context of AF ECV/CA, although small, is not negligible. Patients with higher CHA2DS2-VASc scores, especially older and with larger LA diameter, are more prone to these echocardiographic findings.
MeSH term(s)	Humans ; Atrial Fibrillation ; Retrospective Studies ; Administration, Oral ; Anticoagulants/therapeutic use ; Thrombosis/diagnostic imaging ; Thrombosis/epidemiology ; Thrombosis/etiology ; Heart Diseases/diagnostic imaging ; Heart Diseases/epidemiology ; Echocardiography, Transesophageal ; Atrial Appendage/diagnostic imaging
Chemical Substances	Anticoagulants
Language	Portuguese
Publishing date	2022-10-20
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	730261-7
ISSN	1678-4170 ; 0066-782X
ISSN (online)	1678-4170
ISSN	0066-782X
DOI	10.36660/abc.20210658
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Zs.A 548: Show issues

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Article: Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis.

Cavalcanti, Fernando / Gonzalez-Rey, Elena / Delgado, Mario / Falo, Clara P / Mestre, Leyre / Guaza, Carmen / O'Valle, Francisco / Lufino, Michele M P / Xaus, Jordi / Mascaró, Cristina / Lunardi, Serena / Sacilotto, Natalia / Dessanti, Paola / Rotllant, David / Navarro, Xavier / Herrando-Grabulosa, Mireia / Buesa, Carlos / Maes, Tamara

Pharmaceutics

2022 Volume 14, Issue 7

Abstract: Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A forms a part of protein complexes that regulate the expression of genes involved in the onset and progression of ... ...

Abstract	Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A forms a part of protein complexes that regulate the expression of genes involved in the onset and progression of diseases such as cancer, central nervous system (CNS) disorders, viral infections, and others. Vafidemstat (ORY-2001) is a clinical stage inhibitor of KDM1A in development for the treatment of neurodegenerative and psychiatric diseases. However, the role of ORY-2001 targeting KDM1A in neuroinflammation remains to be explored. Here, we investigated the effect of ORY-2001 on immune-mediated and virus-induced encephalomyelitis, two experimental models of multiple sclerosis and neuronal damage. Oral administration of ORY-2001 ameliorated clinical signs, reduced lymphocyte egress and infiltration of immune cells into the spinal cord, and prevented demyelination. Interestingly, ORY-2001 was more effective and/or faster acting than a sphingosine 1-phosphate receptor antagonist in the effector phase of the disease and reduced the inflammatory gene expression signature characteristic ofEAE in the CNS of mice more potently. In addition, ORY-2001 induced gene expression changes concordant with a potential neuroprotective function in the brain and spinal cord and reduced neuronal glutamate excitotoxicity-derived damage in explants. These results pointed to ORY-2001 as a promising CNS epigenetic drug able to target neuroinflammatory and neurodegenerative diseases and provided preclinical support for the subsequent design of early-stage clinical trials.
Language	English
Publishing date	2022-07-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14071420
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Article ; Online: Comprehensive

Sacilotto, Natalia / Dessanti, Paola / Lufino, Michele M P / Ortega, Alberto / Rodríguez-Gimeno, Alejandra / Salas, Jordi / Maes, Tamara / Buesa, Carlos / Mascaró, Cristina / Soliva, Robert

ACS pharmacology & translational science

2021 Volume 4, Issue 6, Page(s) 1818–1834

Abstract: Lysine-specific demethylase 1 (LSD1 or KDM1A) is a chromatin modifying enzyme playing a key role in the cell cycle and cell differentiation and proliferation through the demethylation of histones and nonhistone substrates. In addition to its enzymatic ... ...

Abstract	Lysine-specific demethylase 1 (LSD1 or KDM1A) is a chromatin modifying enzyme playing a key role in the cell cycle and cell differentiation and proliferation through the demethylation of histones and nonhistone substrates. In addition to its enzymatic activity, LSD1 plays a fundamental scaffolding role as part of transcription silencing complexes such as rest co-repressor (CoREST) and nucleosome remodeling and deacetylase (NuRD). A host of classical amine oxidase inhibitors such as tranylcypromine, pargyline, and phenelzine together with LSD1 tool compounds such as SP-2509 and GSK-LSD1 have been extensively utilized in LSD1 mechanistic cancer studies. Additionally, several optimized new chemical entities have reached clinical trials in oncology such as ORY-1001 (iadademstat), GSK2879552, SP-2577 (seclidemstat), IMG-7289 (bomedemstat), INCB059872, and CC-90011 (pulrodemstat). Despite this, no single study exists that characterizes them all under the same experimental conditions, preventing a clear interpretation of published results. Herein, we characterize the whole LSD1 small molecule compound class as inhibitors of LSD1 catalytic activity, disruptors of SNAIL/GFI1 (SNAG)-scaffolding protein-protein interactions, inducers of cell differentiation, and potential anticancer treatments for hematological and solid tumors to yield an updated, unified perspective of this field. Our results highlight significant differences in potency and selectivity among the clinical compounds with iadademstat being the most potent and reveal that most of the tool compounds have very low activity and selectivity, suggesting some conclusions derived from their use should be taken with caution.
Language	English
Publishing date	2021-11-12
Publishing country	United States
Document type	Journal Article
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.1c00223
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Article ; Online: Correction: Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice.

Overman, Jeroen / Fontaine, Frank / Moustaqil, Mehdi / Mittal, Deepak / Sierecki, Emma / Sacilotto, Natalia / Zuegg, Johannes / Robertson, Avril A B / Holmes, Kelly / Salim, Angela A / Mamidyala, Sreeman / Butler, Mark S / Robinson, Ashley S / Lesieur, Emmanuelle / Johnston, Wayne / Alexandrov, Kirill / Black, Brian L / Hogan, Benjamin M / De Val, Sarah /

Capon, Robert J / Carroll, Jason S / Bailey, Timothy L / Koopman, Peter / Jauch, Ralf / Cooper, Matthew A / Gambin, Yann / Francois, Mathias

eLife

2023 Volume 12

Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Published Erratum
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.90408
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