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www.arquivosonline.com.br Sociedade Brasileira de Cardiologia ISSN-0066-782X Volume 102, N 1, January 2014

EditorialThe Arquivos Brasileiros de Cardiologia and the Dissemination of

Cardiovascular Science Research in Brazil

Special ArticlePrevalence of Heart Disease Demonstrated in 60 Years of the Arquivos

Brasileiros de Cardiologia

Original ArticlesAssessment of the Relationship between Non-Alcoholic Fatty Liver

Disease and CAD using MSCT

A New Tissue Doppler Index to Predict Cardiac Death in Patients with

Heart Failure

Atrial Fibrillation Ablation by Use of Electroanatomical Mapping: Efficacy

and Recurrence Factors

Risk Factors Associated with High Blood Pressure in Two- to Five-Year-

Old Children

Aerobic Interval Exercise Training Induces Greater Reduction in Cardiac

Workload in the Recovery Period in Rats

Cystatin C, CRP, Log TG/HDLc and Metabolic Syndrome are Associated

with Microalbuminuria in Hypertension

Blood Pressure in Adolescence, Adipokines and Inflammation in Young

Adults. The Rio de Janeiro Study

Angiotensin-Converting Enzyme Genetic Polymorphism: Its Impact on

Cardiac Remodeling

Short and Long-Term Outcome of Stress-Induced Cardiomyopathy: What

Can We Expect?

Subcutaneous Tissue Thickness is an Independent Predictor of Image

Noise in Cardiac CT

Brief CommunicationCoronary Obstruction Following Transcatheter Aortic Valve Implantation

Review ArticleThe Echocardiography in the Cardiovascular Laboratory: A Guide to

Research with Animals

Letter to the EditorPossible Brugada Phenocopy Induced by Hypokalemia in a Patient with

Congenital Hypokalemic Periodic Paralysis

Association is Not the Same as Accuracy

Eletronic Pages

Clinicoradiological SessionCase 1/2014 - 24-Year-Old Man with Left Single Ventricle in Chronic

Hypoxia

Case ReportAtypical Clinical Presentation of Arrhythmogenic Biventricular

Cardiomyopathy

ViewpointBack to Basics: PCSK9 as a New Target for the LDL Receptor

ImageFatal Infective Endocarditis in a Patient with Cardiac

Resynchronization Therapy

Figure 2 A) Multiplanar reconstruction image is showing mild stenotic calcified coronary plaques at proximal area of RCA(arrows) (RCA: right coronary artery). B) 3-D reconstruction image are showing mild stenotic calcified coronary plaques at proximal area of RCA(arrows) (RCA: right coronary artery). Page 12

Arquivos Brasileiros de Cardiologia - Volume 102, N 1, January 2014

A JOURNAL OF SOCIEDADE BRASILEIRA DE CARDIOLOGIA - Published since 1948

Contents

Editorial

The Arquivos Brasileiros de Cardiologia and the Dissemination of Cardiovascular Science Research in BrazilLuiz Felipe P. Moreira..........................................................................................................................................................................page1

Special Article

Prevalence of Heart Disease Demonstrated in 60 Years of the Arquivos Brasileiros de Cardiologia

Paulo Roberto Barbosa Evora, Julio Cesar Nather, Alfredo Jos Rodrigues.........................................................................................................................................................................page 3

Original Articles

Atherosclerosis/Endothelium/Vascular

Assessment of the Relationship between Non-Alcoholic Fatty Liver Disease and CAD using MSCTDuran Efe e Fatih Aygn.......................................................................................................................................................................page 10

Echocardiography (Adults)

A New Tissue Doppler Index to Predict Cardiac Death in Patients with Heart FailureCristian Mornos, Lucian Petrescu, Dragos Cozma, Adina Ionac.......................................................................................................................................................................page 19

Therapeutic Electrophysiology (Ablation)

Atrial Fibrillation Ablation by Use of Electroanatomical Mapping: Efficacy and Recurrence FactorsCarlos Kalil, Eduardo Bartholomay, Anibal Borges, Guilherme Gazzoni, Edimar de Lima, Renata Etchepare, Rafael Moraes, Carolina Sussenbach, Karina Andrade, Renato Kalil.......................................................................................................................................................................page 30

Epidemiology

Risk Factors Associated with High Blood Pressure in Two- to Five-Year-Old ChildrenPaula Azevedo Aranha Crispim, Maria do Rosrio Gondim Peixoto, Paulo Csar Brando Veiga Jardim.......................................................................................................................................................................page 39

Exercising

Aerobic Interval Exercise Training Induces Greater Reduction in Cardiac Workload in the Recovery Period in RatsJuliana Pereira Borges, Gustavo Santos Masson, Eduardo Vera Tibiri, Marcos Adriano da Rocha Lessa.......................................................................................................................................................................page 47


Systemic Hypertension

Cystatin C, CRP, Log TG/HDLc and Metabolic Syndrome are Associated with Microalbuminuria in HypertensionRafaela do Socorro Souza e Silva Moura, Daniel Frana Vasconcelos, Eduardo Freitas, Flavio Jos Dutra de Moura, Tnia Torres Rosa, Joel Paulo Russomano Veiga.......................................................................................................................................................................page 54

Systemic Hypertension

Blood Pressure in Adolescence, Adipokines and Inflammation in Young Adults. The Rio de Janeiro StudyErika Maria Gonalves Campana, Andra Araujo Brando, Roberto Pozzan, Maria Eliane Campos Magalhes, Flvia Lopes Fonseca, Oswaldo Luiz Pizzi, Elizabete Viana de Freitas, Ayrton Pires Brando.......................................................................................................................................................................page 60

Heart Failure

Angiotensin-Converting Enzyme Genetic Polymorphism: Its Impact on Cardiac RemodelingFelipe Neves de Albuquerque, Andra Araujo Brando, Dayse Aparecida da Silva, Ricardo Mourilhe-Rocha, Gustavo Salgado Duque, Alyne Freitas Pereira Gondar, Luiza Maceira de Almeida Neves, Marcelo Imbroinise Bittencourt, Roberto Pozzan, Denilson Campos de Albuquerque.......................................................................................................................................................................page 70

Cardiomyopathies

Short and Long-Term Outcome of Stress-Induced Cardiomyopathy: What Can We Expect?Vnia Filipa Andrade Ribeiro, Mariana Vasconcelos, Filipa Melo, Ester Ferreira, Gracieta Malangatana, Maria Jlia Maciel.......................................................................................................................................................................page 80

Computed tomography/Magnetic resonance imaging

Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CTHenrique Lane Staniak, Rodolfo Sharovsky, Alexandre Costa Pereira, Cludio Campi de Castro, Isabela M. Benseor, Paulo A. Lotufo, Mrcio Sommer Bittencourt.......................................................................................................................................................................page 86

Brief Communication

Coronary Obstruction Following Transcatheter Aortic Valve ImplantationHenrique Barbosa Ribeiro, Rogrio Sarmento-Leite, Dimytri A. A. Siqueira, Luiz Antnio Carvalho, Jos Armando Mangione, Josep Rods-Cabau, Marco A. Perin, Fbio Sandoli de Brito Jr........................................................................................................................................................................page 93

Review Article

The Echocardiography in the Cardiovascular Laboratory: A Guide to Research with AnimalsMaria Cristina Donadio Abduch, Renato Samy Assad, Wilson Mathias Jr., Vera Demarchi Aiello .......................................................................................................................................................................page 97


Arquivos Brasileiros de Cardiologia - Eletronic Pages

Clinicoradiological Session

Case 1/2014 - 24-Year-Old Man with Left Single Ventricle in Chronic HypoxiaEdmar Atik, Marcelo B. Jatene, Patricia O. Marques, Fabiana Passos Succi.................................................................................................................................................................... page e1

Case Report

Atypical Clinical Presentation of Arrhythmogenic Biventricular CardiomyopathyIns Rangel, Mariana Vasconcelos, Manuel Campelo, Ceclia Frutuoso, Antnio Jos Madureira, Maria Jlia Maciel.................................................................................................................................................................... page e3

Viewpoint

Back to Basics: PCSK9 as a New Target for the LDL ReceptorPablo Corral.................................................................................................................................................................... page e5

Image

Fatal Infective Endocarditis in a Patient with Cardiac Resynchronization TherapyOscar Fabregat-Andrs e Bruno Bochard-Villanueva.................................................................................................................................................................... page e9

* Indicate manuscripts only in the electronic version. To view them, visit: http://www.arquivosonline.com.br/2013/english/10201/edicaoatual.asp

Letter to the Editor

Possible Brugada Phenocopy Induced by Hypokalemia in a Patient with Congenital Hypokalemic Periodic ParalysisDaniel D. Anselm, Natalia Rodriguez Genaro, Adrian Baranchuk.....................................................................................................................................................................page 104

Association is Not the Same as AccuracyLuis Cludio Lemos Correia e Carolina Esteves Barbosa.....................................................................................................................................................................page 105

Editorial BoardBrasilAdib D. Jatene (SP)Alexandre A. C. Abizaid (SP)Alfredo Jos Mansur (SP)lvaro Avezum (SP)Amanda G. M. R. Sousa (SP)Andr Labrunie (PR)Andrei Sposito (DF)Angelo A. V. de Paola (SP)Antonio Augusto Barbosa Lopes (SP)Antonio Carlos C. Carvalho (SP)Antnio Carlos Palandri Chagas (SP)Antonio Carlos Pereira Barretto (SP)Antonio Cludio L. Nbrega (RJ)Antonio de Padua Mansur (SP)Ari Timerman (SP)Armnio Costa Guimares (BA)Ayrton Klier Pres (DF)Ayrton Pires Brando (RJ)Barbara M. Ianni (SP)Beatriz Matsubara (SP)Braulio Luna Filho (SP)Brivaldo Markman Filho (PE)Bruce B. Duncan (RS)Bruno Caramelli (SP)Carisi A. Polanczyk (RS)Carlos Alberto Pastore (SP)Carlos Eduardo Negro (SP)Carlos Eduardo Rochitte (SP)Carlos Eduardo Suaide Silva (SP)Carlos Vicente Serrano Jnior (SP)Celso Amodeo (SP)Charles Mady (SP)Claudio Gil Soares de Araujo (RJ)Cleonice Carvalho C. Mota (MG)Dalton Valentim Vassallo (ES)Dcio Mion Jr (SP)Denilson Campos de Albuquerque (RJ)Dikran Armaganijan (SP)Djair Brindeiro Filho (PE)Domingo M. Braile (SP)Edmar Atik (SP)Edson Stefanini (SP)Elias Knobel (SP)Eliudem Galvo Lima (ES)Emilio Hideyuki Moriguchi (RS)Enio Buffolo (SP)

Eulgio E. Martinez F (SP)Evandro Tinoco Mesquita (RJ)Expedito E. Ribeiro da Silva (SP)Fbio Sndoli de Brito Jr. (SP)Fbio Vilas-Boas (BA)Fernando A. P. Morcerf (RJ)Fernando Bacal (SP)Flvio D. Fuchs (RS)Francisco Antonio Helfenstein Fonseca (SP)Francisco Laurindo (SP)Francisco Manes Albanesi F (RJ)Gilmar Reis (MG)Gilson Soares Feitosa (BA)nes Lessa (BA)Iran Castro (RS)Ivan G. Maia (RJ)Ivo Nesralla (RS)Jarbas Jakson Dinkhuysen (SP)Joo Pimenta (SP)Jorge Ilha Guimares (RS)Jorge Pinto Ribeiro (RS)Jos A. Marin-Neto (SP)Jos Antonio Franchini Ramires (SP)Jos Augusto Soares Barreto Filho (SE)Jos Carlos Nicolau (SP)Jos Geraldo de Castro Amino (RJ)Jos Lzaro de Andrade (SP)Jos Pricles Esteves (BA)Jos Teles Mendona (SE)Leopoldo Soares Piegas (SP)Lus Eduardo Rohde (RS)Luiz A. Machado Csar (SP)Luiz Alberto Piva e Mattos (SP)Lurildo Saraiva (PE)Marcelo C. Bertolami (SP)Marcia Melo Barbosa (MG)Marco Antnio Mota Gomes (AL)Marcus V. Bolvar Malachias (MG)Maria Cecilia Solimene (SP)Mario S. S. de Azeredo Coutinho (SC)Maurcio I. Scanavacca (SP)Mauricio Wajngarten (SP)Max Grinberg (SP)Michel Batlouni (SP)Nabil Ghorayeb (SP)Nadine O. Clausell (RS)Nelson Souza e Silva (RJ)

Orlando Campos Filho (SP)Otvio Rizzi Coelho (SP)Otoni Moreira Gomes (MG)Paulo A. Lotufo (SP)Paulo Cesar B. V. Jardim (GO)Paulo J. F. Tucci (SP)Paulo J. Moffa (SP)Paulo R. A. Caramori (RS)Paulo R. F. Rossi (PR)Paulo Roberto S. Brofman (PR)Paulo Zielinsky (RS)Protsio Lemos da Luz (SP)Renato A. K. Kalil (RS)Roberto A. Franken (SP)Roberto Bassan (RJ)Ronaldo da Rocha Loures Bueno (PR)Sandra da Silva Mattos (PE)Sergio Almeida de Oliveira (SP)Srgio Emanuel Kaiser (RJ)Sergio G. Rassi (GO)Srgio Salles Xavier (RJ)Sergio Timerman (SP)Silvia H. G. Lage (SP)Valmir Fontes (SP)Vera D. Aiello (SP)Walkiria S. Avila (SP)William Azem Chalela (SP)Wilson A. Oliveira Jr (PE)Wilson Mathias Jr (SP)

ExteriorAdelino F. Leite-Moreira (Portugal)Alan Maisel (Estados Unidos)Aldo P. Maggioni (Itlia)Cndida Fonseca (Portugal)Fausto Pinto (Portugal)Hugo Grancelli (Argentina)James de Lemos (Estados Unidos)Joo A. Lima (Estados Unidos)John G. F. Cleland (Inglaterra)Maria Pilar Tornos (Espanha)Pedro Brugada (Blgica)Peter A. McCullough (Estados Unidos)Peter Libby (Estados Unidos)Piero Anversa (Itlia)

Scientific Director Luiz Alberto Piva e Mattos

chief eDitor Luiz Felipe P. Moreira

ASSociAteD eDitorS

clinicAl cArDiology Jos Augusto Barreto-Filho

SurgicAl cArDiology Paulo Roberto B. Evora

interventioniSt cArDiology Pedro A. Lemos

PeDiAtric/congenitAl cArDiology Antonio Augusto Lopes

ArrhythmiAS/PAcemAker Mauricio Scanavacca

non-invASive DiAgnoStic methoDS Carlos E. Rochitte

BASic or exPerimentAl reSeArch Leonardo A. M. Zornoff

ePiDemiology/StAtiSticS Lucia Campos Pellanda

ArteriAl hyPertenSion Paulo Cesar B. V. Jardim

ergometricS, exerciSe AnD cArDiAc rehABilitAtion Ricardo Stein

firSt eDitor (1948-1953) Jairo Ramos

A JOURNAL OF SOCIEDADE BRASILEIRA DE CARDIOLOGIA - Published since 1948www.arquivosonline.com.br

PresidentAngelo Amato V. de Paola

Vice-PresidentSergio Tavares Montenegro

Financial DirectorJacob Ati

Scientific DirectorMaria da Consolao Vieira Moreira

Administrative DirectorEmilio Cesar Zilli

Assistance Quality DirectorPedro Ferreira de Albuquerque

Communication DirectorMaurcio Batista Nunes

Information Technology DirectorJos Carlos Moura Jorge

Government Liaison DirectorLuiz Csar Nazrio Scala

Director of State and Regional AffairsAbraho Afiune Neto

Cardiovascular Health Promotion Director - SBC/FuncorCarlos Costa Magalhes

Department DirectorEspecializados - Jorge Eduardo Assef

Research DirectorFernanda Marciano Consolim Colombo

Chief Editor of the Brazilian Archives of CardiologyLuiz Felipe P. Moreira

Special Advisor to the PresidencyFbio Sndoli de Brito

Adjunct Coordination

SBC Newsletter EditorNabil Ghorayeb e Fernando Antonio Lucchese

Continuing Education Coordination Estvo Lanna Figueiredo

Norms and Guidelines Coordination Luiz Carlos Bodanese

Governmental Integration Coordination Edna Maria Marques de Oliveira

Regional Integration Coordination Jos Luis Aziz

Presidents of State and Regional Brazilian Societies of Cardiology

SBC/AL - Carlos Alberto Ramos Macias

SBC/AM - Simo Gonalves Maduro

SBC/BA - Mario de Seixas Rocha

SBC/CE - Ana Lucia de S Leito Ramos

SBC/CO - Frederico Somaio Neto

SBC/DF - Wagner Pires de Oliveira Junior

SBC/ES - Marcio Augusto Silva

SBC/GO - Thiago de Souza Veiga Jardim

SBC/MA - Nilton Santana de Oliveira

SBC/MG - Odilon Gariglio Alvarenga de Freitas

SBC/MS - Mrcule Pedro Paulista Cavalcante

SBC/MT - Julio Csar De Oliveira

SBC/NNE - Jose Itamar Abreu Costa

SBC/PA - Luiz Alberto Rolla Maneschy

SBC/PB - Catarina Vasconcelos Cavalcanti

SBC/PE - Helman Campos Martins

SBC/PI - Joo Francisco de Sousa

SBC/PR - Osni Moreira Filho

SBC/RJ - Olga Ferreira de Souza

SBC/RN - Rui Alberto de Faria Filho

SBC/RS - Carisi Anne Polanczyk

SBC/SC - Marcos Vencio Garcia Joaquim

SBC/SE - Fabio Serra Silveira

SBC/SP - Francisco Antonio Helfenstein Fonseca

SBC/TO - Hueverson Junqueira Neves

Sociedade Brasileira de Cardiologia

Presidents of the Specialized Departaments and Study Groups

SBC/DA - Hermes Toros Xavier (SP)

SBC/DCC - Evandro Tinoco Mesquita (RJ)

SBC/DCM - Orlando Otavio de Medeiros (PE)

SBC/DCC/CP - Estela Suzana Kleiman Horowitz (RS)

SBC/DECAGE - Abraho Afiune Neto (GO)

SBC/DEIC - Joo David de Souza Neto (CE)

SBC/DERC - Pedro Ferreira de Albuquerque (AL)

SBC/DFCVR - Jos Carlos Dorsa Vieira Pontes (MS)

SBC/DHA - Weimar Kunz Sebba Barroso de Souza (GO)

SBC/DIC - Jorge Eduardo Assef (SP)

SBC/SBCCV - Walter Jos Gomes (SP)

SBC/SBHCI - Marcelo Antonio Cartaxo Queiroga Lopes (PB)

SBC/SOBRAC - Adalberto Menezes Lorga Filho (SP)

SBC/DCC/GAPO - Daniela Calderaro (SP)

SBC/DCC/GECETI - Joo Fernando Monteiro Ferreira (SP)

SBC/DCC/GEECABE - Luis Claudio Lemos Correia (BA)

SBC/DCC/GEECG - Carlos Alberto Pastore (SP)

SBC/DCP/GECIP - Angela Maria Pontes Bandeira de Oliveira (PE)

SBC/DERC/GECESP - Daniel Jogaib Daher (SP)

SBC/DERC/GECN - Jos Roberto Nolasco de Arajo (AL)

Arquivos Brasileiros de Cardiologia

Affiliated at the Brazilian Medical Association

Volume 102, N 1, January 2014Indexing: ISI (Thomson Scientific), Cumulated Index Medicus (NLM), SCOPUS,

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Editorial

The Arquivos Brasileiros de Cardiologia and the Dissemination of Cardiovascular Science Research in BrazilLuiz Felipe P. MoreiraInstituto do Corao, Hospital das Clnicas, Faculdade de Medicina, Universidade de So Paulo (USP), So Paulo, SP - Brazil

Mailing Address: Luiz Felipe P. Moreira Av. Dr. Enas Carvalho Aguiar, 44, 2 andar, bloco 2, sala 13, Cerqueira Csar. Postal Code 05403-000, So Paulo, SP - BrazilE-mail: [email protected]

KeywordsCardiovascular Diseases; Prevalence; Periodicals as Topic.

DOI: 10.5935/abc.20140002

For over six decades, the development of cardiology and cardiovascular science in Brazil has been documented by the Arquivos Brasileiros de Cardiologia. Over these years, major changes have been observed in various fields of expertise, and new fields of investigation and activity have emerged, significantly transforming the contents of our journal. As we begin a new volume of files at the same time they also started a new period in front of the management of the journal, it is important to highlight the main aspects and trends in publications held. Therefore, it is of great importance that among more than 1,500 original manuscripts published by Brazilian authors on journals indexed by Thomson-Reuters in the database Web of Science regarding cardiovascular topics, from 2010 to 2012, about 27% were published by the Arquivos Brasileiros de Cardiologia, which makes clear the importance of this journal for the Brazilian cardiology science.

With respect to the changes seen in the publications of the Arquivos Brasileiros de Cardiologia throughout its existence, the special article published in this edition, by vora et al., provides an excellent overview on the evolution of the prevalence of major heart diseases based on the manuscripts published over 60 years, during which the journal was indexed at an international level1. Over the period analyzed, we observe a progressive increase in the percentage of publications regarding coronary ar te ry d i sease , myocard ia l in fa rc t ion, hypertension and congestive heart failure - conditions whose prevalence and whose prevention and treatment actions have become increasingly frequent. In parallel, a decrease in the percentage of manuscripts addressing valvular heart diseases, including rheumatic disease, has been documented, as well as those that refer to Chagas disease and cardiac arrhythmias.

Complementing the set of information obtained in the study mentioned, it was observed that in the publications

of the last four years, manuscripts addressing aspects of clinical cardiology, including the monitoring of patients with conditions that include coronary artery disease, heart failure and hypertension accounted for one third of the total number of manuscripts published by the Arquivos. Studies related to basic research and to the study of diagnostic methods, represented about 15% of the publications on an individual basis, while the other areas covered by the journal, such as epidemiology, interventional cardiology, cardiac surgery, cardiac arrhythmia, pediatric cardiology, exercising and rehabilitation, accounted for 3% to 10% of the manuscripts accepted for publication.

Concerning the types of publications, original manuscripts, which represent more than 60% of the studies published by the Arquivos, maintained a distribution similar to the overall distribution of materials accepted for publication. Review manuscripts also focused on the themes of clinical cardiology, basic research and diagnostic methods, while case reports mostly included themes related to interventional cardiology and arrhythmia, in addition to manuscripts related to clinical cardiology and diagnostic methods. The maintenance of regular publications of anatomoclinical and clinical-radiological correlations on each issue of our journal, as well as the points of view of experts of various segments of cardiology, complemented the journals current scientific and informational contents, which cover virtually all fields of knowledge related to cardiology.

Although the aspects presented here partially represent the scope of the Brazilian scientific production in cardiology, they refer solely to the percentage related to manuscripts published in the Arquivos Brasileiros de Cardiologia. Undoubtedly, significant numbers of basic science manuscripts and each of the specific areas of this specialty are published in other channels both in Brazil and in other countries, which represents a major limitation to the generalization of the figures discussed here. Furthermore, it is important to consider the existence of a large number of manuscripts with a considerable scientific merit, which are currently denied by the Arquivos, which has a level of acceptance as low as 25%, publishing around ten original manuscripts per month. In this sense, an increased dissemination of this growing research activity in the context of cardiovascular sciences in our country is necessary, either by creating new journals linked to the Arquivos or by a stronger integration with other cardiology journals published in Brazil.

1

Editorial

Moreira et al.The Arquivos and Brazilian Cardiology Research

Arq Bras Cardiol. 2013; [online].ahead print, PP.0-0

1. Evora PR, Nather JC, Rodrigues AJ. Prevalncia das doenas cardacas ilustrada em 60 anos dos Arquivos Brasileiros de Cardiologia. Arq Bras Cardiol. 2014;102(1):3-9.

References

2

Special Article

Prevalence of Heart Disease Demonstrated in 60 Years of the Arquivos Brasileiros de CardiologiaPaulo Roberto Barbosa Evora, Julio Cesar Nather, Alfredo Jos RodriguesDepartamento de Cirurgia e Anatomia da Faculdade de Medicina de Ribeiro Preto, Universidade de So Paulo (USP), Ribeiro Preto, SP - Brazil

KeywordsCardiovascular Diseases; Prevalence; Periodicals as Topic;

Coronary Artery Disease; Heart Defects, Congenital; Heart Valve Diseases; Cardiomyopathies, Myocardial Infarction.

Arq Bras Cardiol. 2014; 102(1):3-9

Mailing Address: Paulo Roberto Barbosa Evora Rua Rui Barbosa, 367/15, Centro. Postal Code 14015-120, Ribeiro Preto, SP BrazilE-mail: [email protected], [email protected] Manuscript received September 02, 2013, revised manuscript October 29, 2013, accepted October 30, 2013.

DOI: 10.5935/abc.20140001

AbstractConsidering the historical and academic relevance of

the Brazilian Archives of Cardiology (ABC), as its MEDLINE indexing began in 1950, it was assumed as a hypothesis that the analysis of the publications over the last 60 years could reflect the changing trends of heart disease in Brazil.

The study data were collected using a program developed for this purpose, allowing the automatic extraction of information from the MEDLINE database. The study information were collected by searching Brazilian Archives of Cardiology AND selected parameter in English. Four observational groups were determined: (1) major groups of heart diseases (coronary artery disease, valvular heart disease, congenital heart disease and cardiomyopathies); (2) relevant diseases in clinical practice (cardiac arrhythmias, cor pulmonale, myocardial infarction and congestive heart failure); (3) cardiovascular risk factors (hypertension, diabetes, dyslipidemia and atherosclerosis); and (4) group determined due to the growing trend of publications on congestive heart failure seen in previous groups (congestive heart failure, myocardial infarction, rheumatic heart disease and Chagasic heart disease)

All publications within the established groups were described, highlighting the increasing importance of heart failure and diabetes as risk factors. A relatively easy search was carried out, using the computer program developed for literature search covering six decades. Emphasizing the limitations of the study, we suggest the existence of an epidemiological link between cardiac diseases that are prevalent in Brazil and the publications of the Brazilian Archives of Cardiology.

IntroductionThe Brazilian Archives of Cardiology (ABC) memorial

reports that in the first years of its existence, the great challenge for the Brazilian Society of Cardiology (SBC) was to organize

their congresses to make them regular and productive, which, at that time, was a complex and comprehensive task, mainly due to the difficulties in transportation and effective communication at that time.

The second most important task was the creation of its own self-publicizing vehicle, as those in Europe and the United States had great penetration in the Brazilian academic environment, but did not reach the mass of physicians who practiced Cardiology here, especially those represented by general practitioners. The idea of a self-publicizing vehicle was soon put into practice by creating a journal which, at the time, represented a genuine bold action, as it belonged to a still developing specialty, considering that in most medical centers, Cardiology still part of Internal Medicine. This initiative certifies that the founders of the SBC considered, from the beginning, the need for a vehicle that could record and publicize the events and scientific works produced by its members and this initiative was put into practice at its founding, on 14 of August 19431.

With over 60 years - exactly 70 years of existence since its foundation the ABC is the official scientific publication of the SBC and the main vehicle for the dissemination of Brazilian scientific research in the area of cardiovascular sciences. Published in two languages (Portuguese and English) and indexed in major international databases (ISI Web of Science, Cumulated Index Medicus, MEDLINE, EMBASE, Scopus, SciELO and LILACS), the ABC has an average impact factor of 1.2 according to Thompson Reuters. This fact means a factor that is similar to most of the journals indexed in the ISI Web of Science in the field of Cardiology.

Additionally, ABC is currently classified as Qualis B2 by the Coordination of Improvement of Higher Education Personnel (Capes), a situation that contributes to a better score of Graduate Programs with lines of research in cardiovascular sciences2.

Thus, considering the historical and academic relevance of ABC, with its indexing in MEDLINE in 1950, and convinced of the great possibility of the existence of important biases, it was assumed as a hypothesis that the analysis of the publications over a period of 60 years could reflect the changing trends of heart disease in Brazil. This hypothesis defined the rationale of this research, which, in other words, sought to establish the existence of a temporal association between prevalent heart diseases in Brazil and ABC publications.

Methods The study data were collected with the help of a new

software program using LINUX language, developed by one of the authors (JCN), which consisted of an automatic method

3

Special Article

Evora et al.60 years of ABC publications


of MEDLINE database information3. For this purpose, it was sufficient to provide, as filters, a list of words and parameters of interest. Therefore, the information was processed and stored in a Microsoft Excel file with pre-defined formatting. It is worth mentioning that the creation of this program allowed us to collect a large amount of data within a short period of time, making it a tool that will surely be useful in further investigations.

The program is written in Python language, using some libraries as windmill (establishes the interface with the browser, can operate pages with Java, CSV (MEDLINE) and MS- Excel scripts. There is no graphic interface yet, which brings some difficulty, as the program must be handled entirely at the command terminal. The programming of the word list was performed in a text file (. txt) respecting the order of one word per line.

The collected data were manually specified, with this being the most difficult step, as one needs programming knowledge to do so. It is noteworthy that the program works on both Windows and Linux operating systems.

The study information were collected by searching Brazilian Archives of Cardiology AND selected parameter in English. Filters were applied to the results and then the number of publications for each disease was counted. In order to calculate the percentages by decade, a search with the term Brazilian Archives of Cardiology was performed to count the total number of articles published by the journal and indexed in MEDLINE from 1950 on. We inserted a list of search words and parameters that needed to be extracted from each search result. These parameters could be names, dates, or any other word of interest. The program automatically opens all pages and harvests data of interest. The information is collected and then processed in different ways. In this case, the results were divided into decades, calculating the percentages of values in each period in relation to the total, creating an MS - Excel file with the final values .

Four observational groups were determined: (1) major groups of heart diseases (coronary artery disease, valvular heart disease, congenital heart disease and cardiomyopathies); (2) prevalent diseases in clinical practice (cardiac arrhythmias, Cor Pulmonale, myocardial infarction and congestive heart failure); (3) cardiovascular risk factors (arterial hypertension, diabetes, dyslipidemia and atherosclerosis), and (4) group determined due to the growing trend of publications on congestive heart failure (congestive heart failure, myocardial infarction, rheumatic heart disease and Chagasic heart disease).

Studies on human subjects were considered and the results were presented as compositions of vertical bar graphs (absolute values ) and linear graphs (percentage values representing the timeline).

ResultsThe charts have decades as the abscissa and as ordinate

as the number of results of the chosen parameter divided by the total number of results in the decade. Figure 1 portrays the evolution of large groups of cardiac diseases; Figure 2

shows publications related to four parameters determined by their importance in clinical practice. All curves, except that of arterial hypertension, start from zero because the publications start from 1960 on. Figure 3 shows cardiovascular risk factors in the general survey, and Figure 4 shows the curve of heart failure and possible causes.

DiscussionChart data depicted in Figure 1 show that the percentage

of publications on congenital heart disease decreased in the 1960s and increased in the 1970s and remained stable thereafter, with approximately 2% of incidence. The curve of valvular diseases had a peak in the 1950s, decreased sharply in the 1960s and since then has decreased steadily, to 10-14%. The curve of coronary diseases showed a great increase until the 1970s, when it decreased slightly, increasing again in the 1980s, reaching approximately 19% of cases and, since then, has shown a small decrease. Cardiomyopathies showed a great and almost linear increase until the 1980s, when there was a plateau with a maximum of approximately 13%, followed by a decrease until 2010-2013, when it represented approximately 8% of cases.

Thus, considering the main presumed groups of heart disease, we have the following observations:

- Congenital heart diseases, during the six decades, maintained a level of low and stable incidence. This trend continued in the first three years of the 2010s, coinciding with clinical practice;

- There was a predominance of valvular heart disease in the first 2 decades (1950-1970), when studies on coronary diseases reached and surpassed those on valvular heart diseases, probably coinciding with the advent of coronary angiography;

- It is worth mentioning the behavior of cardiomyopathies, of which publications increased and began to show similar incidence to that of valvular heart disease as early as the 1980s. Considering the decrease in Chagas heart disease as a public health problem, would it not be possible to speculate that this increase is related to coronary disease and/or old age?

Data from the charts depicted in Figure 2 show that the curve of myocardial infarction increased in the 1960s and remained virtually unchanged in 1970s. There was another important increase in the 1980s and, as a result, a new plateau, followed by a decrease in the period of 2010-2013. The curve of arrhythmia increased greatly in the 1960s, reaching almost 16% of the articles, followed by an almost linear decrease to approximately 6%. Congestive heart failure only increased during the study period, and this increase was even more significant in the 1980s, reaching approximately 16% in the period of 2010-2013.

Cor Pulmonale remained below 2% until the 1990s, when it showed a small increase, returning to approximately 2% in 2010-2013. When considering the group of publications determined by its importance in clinical practice (arrhythmias, myocardial infarction, congestive heart failure and Cor Pulmonale) and excluding Cor Pulmonale, of which publications remained at a low and stable level, other three parameters showed patterns amenable to interesting discussion:

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- the incidence of articles on cardiac arrhythmias was more prevalent until the 1990s, when it was equaled by publications on myocardial infarction and congestive heart failure, and started to show a steady decrease;

- in the 1990s, there was a perfect balance between the number of publications;

- from 2000 on, there was an extremely interesting fact, namely, the decrease in publications on myocardial infarction and the continuous increase in publications on congestive heart failure. This pattern coincided with the cardiomyopathy pattern, allowing us to repeat the comment on the influence of age and the development of coronary artery disease;

Another consideration between the patterns of incidence of publications on arrhythmias and Cor Pulmonale would be the emergence of other journals specialized in these subjects.

Chart data depicted in Figure 3 show that the curve of hypertension had a great increase in the study period, going from 4% of publications to over 18% in 2010-2013. Diabetes showed a low increase until the 1990s, when it increased significantly, reaching almost 10%. Dyslipidemia showed a low incidence of articles, less than 2% up to the 1980s, when it showed an approximate increase of 4%. Atherosclerosis remained low until the 1990s, when it showed a near linear increase, reaching about 4% of the publications.

Figura 1 - Main groups of heart diseases (coronary artery disease, valvular heart disease, congenital heart disease and cardiomyopathies).

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Thus, the following were observed in the group of risk factors: clear prevalence of publications involving arterial hypertension, an already observed trend of increase in publications about diabetes, and, observing the first 3 years of the 2010s, an increasing trend of publications on diabetes and a slight decrease of studies on myocardial infarction were confirmed.

Finally, the data depicted in Figure 4 show that Chagasic heart disease remained on a plateau until the 1990s, when it showed an almost linear decrease, reaching 2010-2013

with approximately 4% of the results. Rheumatic heart disease decreased from the 1960s on, remaining below 2%. Myocardial infarction showed an increase in almost the entire study period, with plateaus in the 1970s and 1990s, and declined in the early 2010s. Congestive heart failure showed a high and continuous increase in percentage of articles, ranging from approximately 5% to nearly 20% in the 1980s.

Therefore, due to the increasing number of publications on congestive heart failure, a fourth observational group was created, which confirmed the upward trend, when compared

Figura 2 - Prevalent diseases in clinical practice (cardiac arrhythmias, Cor pulmonale, myocardial infarction and congestive heart failure).

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with the number of publications on Chagasic heart disease, rheumatic heart disease and myocardial infarction. As we observed a lower frequency of rheumatic heart disease and a decreasing trend of publications on Chagas disease, we still speculate about the importance of age and of dilated cardiomyopathy due to coronary artery disease.

LimitationsSome observations are relevant because the present is a

manuscript that does not follow the conventional rules of a scientific article. There are, obviously, limitations to the

method: 1) one of them is counting certain articles more than once, as they may appear in the results of more than one selected parameter. For instance, the same article may appear in the results of myocardial infarction and arrhythmia. Nevertheless, the charts clearly show trends of increase and decrease in the percentage of published articles related to selected indicators; (2) throughout its existence, the ABC had its periodicity changed over time and this increased frequency must certainly have some association with the number of articles published4,5; (3) furthermore, from the 1960s on, there was a marked increase in the number of medical

Figure 3 - Cardiovascular risk factors (arterial hypertension, diabetes, dyslipidemia and atherosclerosis).

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schools in Brazil, with a higher number of cardiologists and the growth of institutions that contribute most to the ABC in the country; and (4) the categorizations were arbitrary and therefore it is necessary to admit them, in general, as simplifiers of reality. In the case of this manuscript, we used the categorization of interest at a time period, in a single vehicle of scientific communication and, of course, the authors methodological interest. This type of categorization, when applied over decades, can fall upon an artificial classification.

In conclusion, it was relatively easily to perform a literature search of six decades with the aid of a computer program developed for this purpose. Emphasizing the limitations of the study, we suggest the existence of a temporal relationship between heart diseases that are prevalent in Brazil and ABC publications.

Author contributionsConception and design of the research and Writing of

the manuscript: Evora PRB; Acquisition of data: Nather JC;

Figure 4 - Arbitrated group due to the growing trend of publications on congestive heart failure (congestive heart failure, myocardial infarction, rheumatic heart disease, Chagas heart disease).

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1. PubMed / Medline. [Acessado em 2013 Nov 10]. Disponvel em: http://www.ncbi.nlm.nih.gov/pubmed/

2. Moreira LF. Bem-vindo pgina dos Arquivos Brasileiros de Cardiologia. [Citado em 2013 nov 10]. Disponvel em: http://www.arquivosonline.com.br/2013/

3. Memorial dos Arquivos Brasileiros de Cardiologia: histria da revista. [Citado em 2013 nov 10]. Disponvel em: http://www.arquivosonline.com.br/memorial/historia.asp

4. Amorim DS. Publications of the Arquivos Brasileiros de Cardiologia in the period 1968-1977. Arq Bras Cardiol. 1980;34(1):1-7.

5. Mansur AJ, Abud AS, Albuquerque CP. Publication trends in quarterly, bimonthly and monthly cycles of publication during the five decades of Brazilian Archives of Cardiology. Arq Bras Cardiol. 2000;75(1):1-7.

References

Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content: Evora PRB, Nather JC, Rodrigues AJ.

Potential Conflict of InterestNo potential conflict of interest relevant to this article

was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This study is not associated with any post-graduation program.

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Assessment of the Relationship between Non-Alcoholic Fatty Liver Disease and CAD using MSCTDuran Efe1 and Fatih Aygn2Departamento de Radiologia, Faculdade de Medicina, Mevlana University1, Konya; Departamento de Cirurgia Cardiovascular, Faculdade de Medicina, Mevlana University2, Konya - Turkey

Mailing Address: Fatih Aygn Aksinne Mahallesi Esmeta Sokak n16. Postal Code 42040, Meram-Konya - TurkeyE-mail: [email protected] received March 21, 2013; revised manuscript July 16, 2013; accepted August 23, 2013.

DOI: 10.5935/abc.20130225

Abstract

Background: Some risk factors for atherosclerosis are followed by non-alcoholic fatty liver disease (NAFLD). We wanted to use Multislice computed tomography (MSCT) as technique for searching relationship between NAFLD and coronary artery disease (CAD).

Objective: The relationship between NAFLD and CAD was investigated using MSCT.

Methods: A total of 372 individuals with or without cardiac symptoms who had undergone MSCT angiography were included in the study. The patients were divided into two groups according to the presence of NAFLD. Coronary artery segments were visually evaluated via MSCT angiography. Based on the coronary artery stenosis degree, those with no or minimal plaques were considered normal, whereas those who had stenosis of less than 50% and at least one plaque were considered to have non-obstructive coronary artery disease (non-obsCAD). The patients who had at least one plaque and coronary artery stenosis of 50% or more were considered to have obstructive coronary artery disease (obsCAD). NAFLD was determined according to the MSCT protocol, using the liver density.

Results: According to the liver density, the number of patients with non-alcoholic fatty liver disease (group 1) was 204 (149 males, 54.8%) and with normal liver (group 2) was 168 (95 males, 45.2%). There were 50 (24.5%) non-obsCAD and 57 (27.9%) obsCAD cases in Group 1, and 39 (23.2%) non-obsCAD and 23 (13.7%) obsCAD cases in Group 2.

Conclusions: The present study using MSCT demonstrated that the frequency of coronary artery disease in patients with NAFDL was significantly higher than that of patients without NAFDL. (Arq Bras Cardiol. 2014; 102(1):10-18)

Keywords: Fatty Liver; Hepatitis; Metabolic x Syndrome; Coronary Artery Disease; Atherosclerosis, Tomography.

IntroductionToday, non-alcoholic fatty liver disease (NAFLD) is considered

as the most common chronic liver disease in Western populations1,2. Since the cases are generally asymptomatic, the true prevalence of NAFLD is unknown. Hepatic enzymes are within normal ranges in 70% of the patients. Adult screening studies found the prevalence of NAFLD to be 10%-15% in normal-weight individuals, but 70%-80% in obese people3,4. NAFLD comprises a wide spectrum of hepatic damage ranging from simple steatosis and steatohepatitis to advanced fibrosis and cirrhosis3. Risk factors for atherosclerosis including hypertension, obesity, diabetes, metabolic syndrome, dyslipidemia and insulin resistance, accompany NAFLD5-8.

Computed tomography (CT) is the right modality for detecting fatty liver disease9. The attenuation value differences between liver and spleen are used for hepatosteatosis diagnosis. The mean liver attenuation value minus the mean spleen attenuation value presenting a difference of 10 Hounsfield Units indicates hepatosteatosis9,10.

Multislice computed tomography (MSCT) coronary angiography is considered a non-invasive modality for the detection and classification of coronary artery disease (CAD)11,12.

The present study investigated the relation between CAD and non-alcoholic fatty liver disease using MSCT angiography protocol.

Methods

Patients Clinical Characteristics The present study comprises 372 patients with or

without cardiac symptoms, who underwent MSCT angiography in our clinic between January 2008 and September 2012. Data were collected retrospectively and the ethical committee approval was obtained.

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Efe & AygnNAFLD, MSCT, CAD

Arq Bras Cardiol. 2014; 102(1):10-18

Study groups included individuals who did not consume alcohol or had an alcohol consumption of less than 20 g/day ethanol. People with positive serology for hepatitis B or C or who had a history of chronic liver disease were excluded from the study.

Dyslipidemia was defined as a fasting serum triglyceride level 150 mg/dl, low-density lipoprotein (LDL) cholesterol level 140 mg/dl, and/or high-density lipoprotein (HDL) cholesterol level < 40 mg/dl, and those receiving or not active medical treatment for this13.

Before CT scan, the height (Human weighing machine, NAN TARTI A, Turkey) and body weight (TANITA Body Composition Analyzer, TANITA Corporation, Japan) of the participants were measured, and their body mass indexes (BMI) were calculated. Those with a BMI lower than 25 kilogram (kg)/square meter (m2) (BMI

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Arq Bras Cardiol. 2014; 102(1):10-18

Figure 1 - 3-D reconstruction image are showing normal coronary arteries (RCA: right coronary artery; Cx: circumflex coronary artery; LAD: left anterior descending artery).

Figure 2 - A) Multiplanar reconstruction image is showing mild stenotic calcified coronary plaques at proximal area of RCA(arrows) (RCA: right coronary artery). B) 3-D reconstruction image are showing mild stenotic calcified coronary plaques at proximal area of RCA(arrows) (RCA: right coronary artery).

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Figure 3 - A) Multiplanar reconstruction image is showing total vessel occlusion of the right coronary artery due to diffuse soft plaque (arrows). B) 3-D reconstruction image is showing considerable atherosclerosis with diffuse calcifications of LAD and Cx (arrows)(LAD: the left anterior descending artery; Cx: circumflex coronary artery).

Figure 4 - Diffuse fat deposition in the liver (non-contrast CT section). Liver density is 37 HU and spleen density is 68 HU.

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Table 1 - Data and statistical results about groups

Group 1 (n = 204) Group 2 (n = 168) p value

Age (SD) 50,8 10,9 48,09 11,5 0,018

Gender (male) 149 (% 73) 95 (% 56,5) 0,001

Hepatic density (HU) 43,7 9 62,2 5,2 0

Diabetes

Nondiabetic 130 (% 63,7) 124 (% 73,8)

0,112Oral a/d 54 (% 26,5) 33 (% 19,8)

Parenteral a/d 20 (% 9,4) 11 (% 6,5)

Dyslipidemia 161 (% 78,9) 108 (% 64,3) 0,002

Hypertension 125 (% 61,3) 94 (% 56) 0,323

Smoking 96 (% 47,1) 56 (% 33,3) 0,007

Alcohol consumption 20 g/day ( SD) - - -

Body weight

Excessive weight 61 (% 29,9) 39 (% 23,2)0

Obesity 104 (% 51) 34 (% 20,2)

CAD disease

Non-obs CAD 50 (% 24,5) 39 (% 23,2)0,002

Obs CAD 57 (%27,9) 23 (% 13,7): P value was presented as a result of Student t-test. : P value was presented as a result of Pearson Chi-square test. SD: Standart deviation; HU: Haunsfiled Unit; a/d: Antidiabetic agent; CAD: Coronary artery disease; non-obs: Non-obstructive; obs: Obstructive.

Table 2 - Statistical effect of different characteristics in groups

Unadjusted OR %95 CI p value Adjusted OR %95 CI p value

Age ( SD) 1,082 1,039-1,127 0,000 1,065 1,029-1,101 0,000

Gender 2,498 0,972-6,425 0,057 - - -

Dyslipidemia 0,111 0,035-0,355 0,000 0,121 0,039-0,377 0,000

Smoking 1,883 0,840-4,223 0,125 - - -

OR: Odds Ratio; SD: Standart deviation.

There were 152 (40.9%) active smokers and 220 (59.1%) nonsmokers. Based on BMI, 96 (25%) patients were normal-weight, 149 (40.1%) were over-weight and 127 (34.1%) were obese. Fatty liver disease was detected in 168 (45.2%) of study participants. Number of patients with normal liver was 204 (54.8%). (Table 3)

The mean liver density was 43 9.1 HU (range 14-56) in males, and 45.5 8.4 HU (range 31-58) in females of Group 1. The corresponding figures were 61.8 4.7 HU (range, 56-75), and 62.6 5.7 HU (range, 54-74) in the males and females of Group 2, respectively. Mean liver densities of the groups according to their ages are demonstrated in Figure 5.

Evaluation of the coronary arteries of the study participants revealed that 203 of them (107 males, 52.7%) had normal coronary arteries, 89 (69 males, 77.5%) had non-obsCAD, and 80 (68 males, 21.5%) had obsCAD.

The number of males without coronary artery disease was 62 (41.6%), those with non-obsCAD was 42 (28.2%), and those with obsCAD was 45 (30.2%) in Group 1. The number of females without coronary artery disease was 35 (63.6%), with non-obsCAD was 8 (14.5%), and with obsCAD was 12 (21.8%).

In Group 2, there were 45 (47.4%) males without coronary artery disease, 27 (28.4%) males with non-obsCAD, and 23 (24.2%) males with obsCAD. The number of females without coronary artery disease was 61 (83.6%), with non-obsCAD was 12 (16.4%), and with obsCAD was 0 in Group 2.

Individuals in Group 1 were older and dyslipidemic more than Group 2. In additionaly, Group 1 has more males and smokers than the Group 2. These characteristics of persons affected on obsCAD were evaluated with Binary Logistic Regresion Analysis in Table 3. Age and dyslipidemia affected on obsCAD were considered statistical significant (p < 0.01).

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Table 3 - Data about study participants

All participants ( n = 372)

Age ( SD) 49.6 11,2 years( range 24-74 years)

Gender (male) 244 (65,6%)

Hepatic density (HU) 52 11.9 HU (range, 14-75 HU)

Diabetes

Nondiabetic 239 (64.2%)

Oral a/d 96 (25.8%)

parenteral a/d 37 (9.9%)

Dyslipidemia 131 (35,2%)

Hypertension 102 (27,4%)

Smoking ( active smokers) 152 (40,9%)

Alcohol consumption 20 g/day ( SD) -

Body weight

Excessive weight 149 (40.1%)

Obesity 127 (34.1%): P value was presented as a result of Student t-test. : P value was presented as a result of Pearson Chi-square test. SD: Standart deviation; HU: Haunsfiled Unit; a/d: Antidiabetic agent.

Figure 5 - Mean hepatic density according to ages.

Mean

hep

atic

dens

ity

AgeError bars: 95 CI

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DiscussionMSCT coronary angiography is an important method for

detecting CAD in the early stage. A study which compared MSCT angiography and invasive coronary angiography for the evaluation of coronary arteries and coronary artery segments larger than 1.5 mm found the sensitivity of MSCT angiography to be 94% and specificity to be 97%14. Besides, CT is also used for the diagnosis of hepatic steatosis. Sensitivity and specificity of CT for the diagnosis of hepatic steatosis is 82% and 100%, respectively9. The present study used the hepatic CT images used in the MSCT angiography scanning protocol.

Based on MSCT, the present study found that coronary artery disease prevalence in patients with NAFLD was significantly higher than that of those with normal liver tissue (p < 0.01). Statistical comparison between the two groups is presented in Table 2.

Studies from other countries reported that NAFLD was more common among females15,16. However, a study from Turkey found the frequency of non-alcoholic hepatic steatosis to be lower in females (32.7%)17. Some prevalence studies verified the diagnosis of NAFLD in 76% of 146 liver biopsy samples obtained from obese patients that underwent bariatric surgery; a smaller-scale study in Turkey, however, reported the prevalence of NAFLD to be 72% among obese patients18,19.

A gradually increasing number of studies indicate NAFLD as the hepatic manifestation of metabolic syndrome20,21. Although metabolic syndrome is a well-known precursor of CAD22-24, the association between NAFLD and CAD remains unclear.

There are studies demonstrating that proinflammatory cytokines including tumor necrosis factor alpha (TNF-), C reactive protein (CRP) and plasminogen activator inhibitor I (PAI-I) have been increased in patients with both NAFLD and CAD25. It has been emphasized that the increase in proinflammatory markers enhances future CAD events25. It has been also highlighted that this might independ from metabolic syndrome and related risk factors. Some studies conducted in insulin users demonstrated that insulin resistance is a predictor for CAD events and plays an important role in the development of unfavorable clinical outcomes for NAFLD patients26,27.

Association between NAFLD, from simple steatosis to advanced form of NAFLD, and high risk of CAD has been attributed to increased oxidative stress and subclinical inflammation26,28,29.

A study conducted by Perseghin stated that NAFLD was characterized by the appearance of early metabolic and vascular pathological changes of atherosclerosis. However, despite all these findings, it has been emphasized that the evidences indicating the association between NAFLD and CAD are weak30.

Although the close association between NAFLD and CAD has not been clarified yet, fat deposition in NAFLD is considered to increase free fatty acids that lead to CAD by causing low-grade inflammation31. The presence of NAFLD in patients with type 2 diabetes has suggested NAFLD as a strong predictor for CAD32.

Brea et al33 found an association between NAFLD and carotid atherosclerosis. Targher et al34 suggested a relation between NAFLD and carotid artery wall thickness in type 2 diabetes mellitus patients controlled with diet. Lin et al35 stated that NAFLD was an independent risk factor for ischemic CAD.

Study LimitationsWhile measuring the liver density of some cases,

the optimal selection of appropriate hepatic regions not including vascular and biliary structures has not been possible due to inadequate spatial resolution. During MSCT coronary angiography, we had occasional difficulties in detecting the stenosis degree in massive calcified plaques. Moreover, there have been difficulties in differentiating probable coronary artery soft plaques from the respiratory artifacts on the images of the cases with respiratory distress.

ConclusionBased on MSCT, the present study found that the difference

between the prevalence of coronary artery disease found in the group with NAFLD and in the group with normal liver tissue was statistically significant.

We can say that the likelihood of CAD in individuals with hepatosteatosis not consuming or consuming less than 20 g/day of alcohol is higher than in the individuals without hepatosteatosis.

We think that this hypothesis should be verified with larger studies.

AcknowledgmentsWe thank Assoc. Prof. Ismail Keskin*, PhD for his

contributions to the evaluation of results and statistical analysis.*Seluk University, Zootechnics Division, Department of

Biometry and Genetics, Konya, TURKEY.

Author contributionsConception and design of the research, Acquisition of

data, Analysis and interpretation of the data: Efe D. Statistical analysis, Writing of the manuscript, Critical revision of the manuscript for intellectual content: Aygn F.

Potential Conflict of InterestNo potential conflict of interest relevant to this article was

reported.

Sources of FundingThere were no external funding sources for this study.

Study AssociationThis study is not associated with any post-graduation

program.

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32. Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005;54(12):3541-6.

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34. Targher G, Bertolini L, Padovani R, Poli F, Scala L, Zenari L, et al. Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients. J Endocrinol Invest. 2006;29(1):55-60.

35. Lin YC, Lo HM, Chen JD. Sonographic fatty liver, overweight and ischemic heart disease. World J Gastroenterol. 2005;11(31):4838-42.

References

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Arq Bras Cardiol. 2014; 102(1):10-1818

Original Article

A New Tissue Doppler Index to Predict Cardiac Death in Patients with Heart FailureCristian Mornos1,2, Lucian Petrescu1,2, Dragos Cozma1,2, Adina Ionac1,2Victor Babes University of Medicine and Pharmacy1, Timisoara; Institute of Cardiovascular Diseases2, Timisoara - Romania

Mailing Address: Lucian Petrescu Victor Babes University of Medicine and Pharmacy, Timisoara, G.Adam 13 - RomaniaE-mail: [email protected] Manuscript received March 25, 2013; revised manuscript July 20, 2013; accepted August 07, 2013.

DOI: 10.5935/abc.20130222

AbstractBackground: It has been shown that a new tissue Doppler index, E/(ES), including the ratio between early diastolic transmitral and mitral annular velocity (E/E), and the systolic mitral annular velocity (S), has a good accuracy to predict left ventricular filling pressure.

Objectives: We investigated the value of E/(ES) to predict cardiac death in patients with heart failure.

Methods: Echocardiography was performed in 339 consecutive hospitalized patients with heart failure, in sinus rhythm, after appropriate medical treatment, at discharge and after one month. Worsening of E/(ES) was defined as any increase of baseline value. The end point was cardiac death.

Results: During the follow-up period (35.2 8.8 months), cardiac death occurred in 51 patients (15%). The optimal cut-off value for the initial E/(ES) to predict cardiac death was 2.83 (76% sensitivity, 85% specificity). At discharge, 252 patients (74.3%) presented E/(ES) 2.83 (group I) and 87 (25.7%) presented E/(ES) > 2.83 (group II), respectively. Cardiac death was significantly higher in group II than in group I (38 deaths, 43.7% vs. 13 deaths, 5.15%, p < 0.001). By multivariate Cox regression analysis, including variables that affected outcome in univariate analysis, E/(ES) at discharge was the best independent predictor of cardiac death (hazard ratio = 3.09, 95% confidence interval = 1.81-5.31, p = 0.001). Patients with E/(ES) > 2.83 at discharge and its worsening after one month presented the worst prognosis (all p < 0.05).

Conclusions: In patients with heart failure, the E/(ES) ratio is a powerful predictor of cardiac death, particularly if it is associated with its worsening. (Arq Bras Cardiol. 2014; 102(1):19-29)

Keywords: Heart Failure / mortality; Echocardiography, Doppler; Death, Sudden, Cardiac / prevention & control.

useful information regarding LV filling pressure9. However, elevated LV filling pressure may be clinically silent. The early diastolic transmitral velocity/early mitral annular diastolic velocity ratio (E/E) has been proposed as the best single Doppler predictor for evaluating LV filling pressure12,13 and as a good predictor of cardiac death1,5,6,9,10. Recently, a new TDI index, E/(ES), that associates a marker of diastolic function (E/E) and a parameter that explores LV systolic performance (systolic mitral annular velocity, S), had been shown to be useful to assess the LV filling pressure in a heterogeneous population of cardiac patients, regardless of LVEF14.

We believe that a precise assessment of prognosis in patients with cardiac diseases must take into account parameters that explore global LV function. Therefore, we investigated the value of E/(ES) ratio to predict cardiac death in patients with HF.

Methods

PatientsWe analyzed prospectively 500 consecutive patients,

hospitalized at our clinic between October 2006 and September 2007 with HF, in sinus rhythm. We included adult patients (age 18 years) with exacerbation of symptoms of

IntroductionThe mortality rate after the onset of heart failure (HF)

remains high despite recent advances in the management of this condition. The high mortality associated to left ventricular (LV) dysfunction results in the necessity to obtain prognosis information as soon as possible. A variety of indexes derived using echocardiography have been used to predict cardiac outcome of patients with HF, including left cavity dimensions, LV ejection fraction (LVEF), and transmitral flow patterns1-4. Some studies demonstrated that tissue Doppler imaging (TDI) parameters were capable of adding prognostic information to predict cardiac death in major cardiac diseases, such as HF3,5-7, acute coronary syndrome8,9, acute myocardial infarction10, and hypertension11.

Echocardiography is a mainstay of the diagnostic work-up of dyspneic patients2, with Doppler echocardiography providing

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Mornos et al.A Tissue Doppler index to predict cardiac death

Arq Bras Cardiol. 2014; 102(1):19-29

HF with at least 1 New York Heart Association (NYHA) class deterioration, with typical signs of HF and echocardiographic evidence of systolic and/or diastolic LV dysfunction15. Patients with inadequate echocardiographic images, congenital heart disease, cardiac pacemaker/defibrillator, significant primary valvular heart disease, acute coronary syndrome at inclusion, coronary revascularization during follow-up, severe pulmonary disease, malignant neoplasia or renal failure, were excluded. The remaining 339 patients formed our study group. The study was approved by the local research ethics committee.

EchocardiographyBefore discharge and in a reasonably stable clinical

condition (within 24 hour), our patients underwent an echocardiographic examination with an ultrasonographic system (Vivid 7 General Electric, Milwaukee, WI) equipped with multifrequency transducer. LVEF was calculated from apical two- and four-chamber views using a modified Simpsons rule16. Left atrial (LA) volume was calculated using the biplane area-length method at the apical four-chamber and apical two-chamber views at ventricular end-systole (maximum LA size). LA volume was indexed for body surface area16. The severity of mitral regurgitation was assessed from the apical views using proximal convergence method; the regurgitant orifice area (ROA) and the regurgitant volume (RV) were determined17. Transmitral flow patterns were recorded from apical four-chamber windows with 4-5 mm pulsed-sample Doppler volume placed between mitral valve tips in diastole during five consecutive cardiac cycles. Care was taken to obtain the smallest possible angle between the direction of transmitral flow and the ultrasound beam. Maximal velocities of E and late transmitral flow (A) waves were measured during end-expiratory apnea; the velocities were recorded for five consecutive cardiac cycles, and the results were averaged. Pulsed Doppler signals were recorded at a horizontal sweep of 100 mm/s. The global myocardial index (GMI) was determined using Doppler time intervals measured from mitral inflow and LV outflow Doppler tracings as the sum of isovolumic contraction and relaxation time divided by the ejection time18. Measurement of systolic pulmonary artery pressure was performed using the maximal regurgitant velocity at the tricuspide valve by continous Doppler.

The TDI program was set in pulsed-wave Doppler mode. Motion of mitral annulus was recorded in the apical four-chamber view at a frame rate of 80 to 140 frames per second19. A 4-5 mm sample volume was positioned sequentially at the lateral and septal corners of the mitral annulus. The peak early diastolic mitral annular velocity (E) was determined. The peak mitral annular systolic velocity (S) was defined as the maximum velocity during systole, excluding the isovolumic contraction. All velocities were recorded for five consecutive cardiac cycles during end-expiratory apnea, and the results were averaged. All TDI signals were recorded at horizontal time sweep set at 100 mm/s accordingly to current guidelines19. E/E and E/(ES) were calculated; the average of the velocities from the septal and lateral site of the mitral annulus was

used for the analysis. TDI measurements were repeated one month after hospital discharge (30 3 days). Worsening of E/(ES) was defined as a value greater than the previous value determined at discharge. An experienced echocardiographer performed all measurements.

The inter- and intra-observer variabilities for E/E, S and E/(ES) were examined. Measurements were performed in a group of 30 randomly selected subjects by one observer at two separate times and by two investigators who were unaware of the others measurements and of the study time point.

Clinical Variables Recorded The following clinical variables were recorded at hospital

discharge and included in the prognostic model: age, sex, body mass index, mean arterial pressures, heart rate, etiology of HF, NYHA functional class, N-terminal pro-brain natriuretic peptide (NTproBNP) levels (determined within 30 minutes before or after echocardiography). Prescription of the main therapeutic classes in HF was also recorded.

Clinical OutcomePatients were followed for 24 months. Cardiac death

was regarded as the study end- point. The cause of death was determined from hospital documentation, information from attending physicians and death certificate. Cardiac death was defined as a death directly related either to cardiac disease, mainly congestive HF, or sudden death. Non-cardiac death was defined as a death that was not primarily due to cardiac causes.

Statistical Analysis

Data are expressed as mean standard deviation for continuous variables and as proportions for categorical variables. Continuous variables were compared between groups using unpaired t test (variables with normal distribution) or Mann-Whitney U test (non-normally distributed variables). Proportions were compared using chi-square test and Fischers exact test. Univariate Cox proportional hazards analysis was performed to investigate the significance of a number of variables in predicting cardiac death. Variables associated with outcome were put into a multivariate Cox regression model to identify independent predictors of cardiovascular death. The output of this analysis was expressed as hazard ratio with 95% confidence interval. Cumulative mortality curves were obtained using the Kaplan-Meier method. Patients who died of non-cardiovascular causes were censored (as non-events) at date of death. A p value < 0.05 was considered significant. Receiver-operator characteristic (ROC) curves were plotted to define cut-off values of independent predictors. Intra-observer variability and inter-observer variability for E/E, S and E/(ES) were measured by the intraclass correlation coefficient and by the coefficient of variation (CV) with the root-mean-square method. The power calculation was conducted using the PS software version 3.0 from Vanderbilt University (Nashville, TN). For the power calculation, the threshold for significance was = 0.05 and the accrual time was 12 months. All other analyses were carried out with the

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SPSS, version 18.0 (SPSS Inc., Chicago, Illinois) statistical software. This work was supported by CNCSIS-UEFISCU, project number PN II/RU, code PD 526/2010 and TD 530/2007.

ResultsThe current study included 339 consecutive patients

(62 13 years; 106 women), hospitalized for HF, in sinus rhythm. The aetiology of HF was coronary artery disease (218 patients), non-ischemic cardiomyopathy (85 patients) and systemic hypertension (36 patients). The mean LVEF was 41 14% and mitral annular velocities from TDI were recordable at both sites in all 339 patients. Baseline characteristics of the overall group are presented in Table 1.

During the follow-up period (average: 35.2 8.8 months) cardiac death occurred in 51 patients (15%). The clinical and echocardiographic characteristics of the group of survivors and non-survivors are presented in Table 2. As compared with patients who did not develop cardiac death, patients who developed cardiac death had significantly higher NTproBNP

levels and pulmonary artery systolic pressures, larger LA and LV, lower LVEF, E and S velocities and higher values for E, E/A, E/E and E/(ES). In addition, there was no difference with regard to the distribution of age, gender, etiology of HF, heart rate, mean arterial pressure, body mass index, NYHA class, medication (regarding beta blocker, angiotensin converting enzyme inhibitor/angiotensin receptor antagonist, nitrates and diuretics), E-deceleration time, ORA, RV and GMI. Mean E/(ES) at discharge was 3.67 1.69 in patients who developed cardiac death, while it was 1.05 1.09 in the rest (p < 0.001).

Figure 1 shows the ROC curve for E/(ES) at discharge to predict cardiac death. The optimal cut-off value for E/(ES) ratio was 2.83 with 76% sensitivity and 85% specificity. Patients were divided into 2 groups according to E/(ES) at discharge: group I consisted of patients with E/(ES) 2.83 (252 patients, 74.3%) and group II with E/(ES) > 2.83 (87 patients, 25.7%). KaplanMeier analysis showed that the survival rate during follow-up was significantly higher in group I than in group II (log rank, p < 0.001) (Figure 2a). The median survival time from the baseline echocardiography

Table 1 - Baseline characteristics of the overall group of 339 patients with heart failure

Characteristics Data

Clinical characteristics

Age, years 62 13

Female/male gender, n (%) 106 (31.3) / 233 (68.7)

Body mass index, kg/m2 26.1 4.1

Heart rate, beats/min 75.5 21

Mean arterial pressure, mmHg 97.2 14.1

Coronary artery disease, n (%) 218 (64.3)

Non-ischemic cardiomyopathy, n (%) 85 (25.1)

Systemic hypertension, n (%) 36 (10.6)

NYHA class I/II/III/IV, n (%) 20 (5.9)/167 (49.3)/133 (39.2)/19 (5.6)

NTproBNP, pg/ml 3049 3993

Medical therapy

Beta blocker, n (%) 297 (87.6)

ACEI/angiotensin receptor antagonist, n (%) 323 (95.3)

Diuretics, n (%) 294 (86.7)

Digoxin, n (%) 84 (24.8)

Nitrates, n (%) 223 (65.8)

Echocardiographic parameters

LV ejection fraction, % 41 14

Left atrial volume, ml 92 44

Indexed left atrial volume, ml/m2 48 25

Systolic pulmonary artery pressure, mmHg 40 15

Mitral regurgitant orifice area, mm2 27.1 10.1

Mitral regurgitant volume, ml 37.6 14

ACEI: angiotensin converting enzyme inhibitor; LV: left ventricle; NTproBNP: N-terminal pro-brain natriuretic peptide; NYHA: New York Heart Association.

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Table 2 - Clinical and echocardiographic characteristics of the groups of patients at hospital discharge

Characteristics Survivors (n = 288) Cardiac death (n = 51) p value

Clinical characteristics

Age, years 61.8 12.9 64.1 11.1 0.22

Female/male gender 88 / 200 18 / 33 0.51

Body mass index, kg/m2 25.73.8 28.4 5.9 0.43

Heart rate, beats/min 75 17 78 22 0.47

Mean arterial pressure, mmHg 97.7 13.8 94.8 15.7 0.56

Coronary artery disease, n (%) 186 (64.6) 32 (62.7) 0.80

Non-ischemic cardiomyopathy, n (%) 74 (25.7) 11 (21.6) 0.53

Systemic hypertension, n (%) 28 (9.7) 8 (15.7) 0.20

NYHA class I/II/III/IV, n 17/140/118/13 3/27/15/6 0.13

NTproBNP, pg/ml 2454 3039 6411 6418 < 0.001

Medical therapy

Beta blocker, n (%) 254 (88.1) 43 (84.3) 0.73

ACEI/angiotensin receptor antagonist, n (%) 276 (95.8) 47 (92.1) 0.25

Diuretics, n (%) 247 (85.7) 47 (92.1) 0.21

Digoxin, n (%) 64 (22.2) 20 (39.2) 0.01

Nitrates, n (%) 187 (64.9) 36 (70.5) 0.43

Echocardiographic variables

LV end-diastolic volume index, ml/m2 92 32 113 41 0.005

LV end-systolic volume index, ml/m2 53 26 75 29 0.008

LV ejection fraction, % 42 14 33 15 0.001

Left atrial volume, ml 87 40 118 49 < 0.001

Indexed left atrial volume, ml/m2 45 22 65 29 < 0.001

Systolic pulmonary artery pressure, mmHg 39 14 47 18 0.001

Global myocardial index 0.61 0.42 0.72 0.45 0.07

Mitral regurgitant orifice area, mm2 26.6 10.3 29.9 9.8 0.41

Mitral regurgitant volume, ml 37 15 41 22 0.22

E, cm/s 79 25 101 33 < 0.001

E/A ratio 1.14 0.76 1.64 1.08 0.003

E-deceleration time, ms 171 75 158 71 0.27

E, cm/s 7.4 2.7 5.5 1.6 < 0.001

S, cm/s 6.9 2.6 5.1 1.9 < 0.001

E/E ratio 10.9 4.02 18.7 5.91 < 0.001

E/(ES) ratio 1.57 1.09 3.67 1.69 < 0.001

A: late transmitral flow velocity; ACEI: angiotensin converting enzyme inhibitor; E: early diastolic transmitral flow velocity; E: early mitral annular diastolic velocity; LV: left ventricle; NYHA: New York Heart Association; S: systolic velocity of mitral annulus; NTproBNP: N-terminal pro-brain natriuretic peptide.

was 42.1 months in the group of patients with E/(ES) 2.83 and 26.2 months in those with E/(ES) > 2.83. Statistical analysis showed a power of 81% to detect the difference between median survival times for the two groups. To investigate the possible impact of LVEF, patients with LVEF 50% (108 patients, 31.9%) and with LVEF < 50% (231 patients, 68.1%) were analyzed separately. In both

groups, the survival rate was significantly higher in patients from group I than in those from group II, as shown by Kaplan-Meier plots (Figures 2b and 2c).

Table 3 shows the variables that predicted cardiac death on univariate Cox regression analysis (p < 0.05): NTproBNP levels, LVEF, systolic pulmonary artery pressure, indexed LA volume, E/A ratio, E, S, E/E, E/(ES), and LVEF 40%

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combined with E/E >15. Conversely, age, sex, heart rate, blood pressure, etiology of HF (coronary artery disease, etc.), NYHA functional class, LV end-diastolic volume index, LV end-systolic volume index, GMI, E-deceleration time, A, RV and ROA, were not significantly associated with cardiac death on univariate analysis. Only variables that affected outcome were included in the multivariate forward Cox regression analysis. This analysis identified E/(ES) at discharge as the best independent predictor of cardiac death in patients with HF (HR = 3.09, 95% confidence interval = 1.81-5.31, p = 0.001). Table 3 shows the final multivariate Cox model. Non-cardiac death was similar in group I compared to group II [4 (1.58%) vs. 2 (2.29%), p = 0.66].

The additional benefit of E/(ES) to predict cardiovascular death is shown in Figure 3. However, the addition of E/(ES) markedly improved the prognostic utility of the model containing LVEF, indexed LA volume, E/E and S. We included in this model only the t radi t ional echocardiographic parameters and not all of the variables that predicted cardiac death on univariate analysis.

One month after hospital discharge we identified worsening of E/(ES) ratio in 97 patients (28.6%). Of these patients, 37 (10.9%) presented the initial value of E/(ES) greater than 2.83. However, as shown in Figure 4, E/(ES) worsening was associated with lower survival rate, regardless of the E/(ES) value at inclusion in the study (43.2% versus 66%, p = 0.021 in patients with the initial E/(ES) > 2.83, and 90.3% vs. 96.3%, p = 0.046 in those with E/(ES) 2.83 at hospital discharge, respectively). The subgroup of patients with an initial E/(ES) ratio > 2.83 and its worsening after one month presented the worst prognosis in the overall population, and in those with preserved or reduced LVEF (Figures 4

and 5). This analysis was underpowered (< 80%) because of small sample size, small difference in median survival, and subgroup comparisons.

The intra-observer intraclass coefficients for E/E, S and E/(ES) were 0.95 (CV 2.6%), 0.93 (CV 3.1%), and 0.93 (CV 3%), respectively. The inter-observer intraclass coefficients for E/E, S and E/(ES) were 0.93 (CV 2.8%), 0.91 (CV 3%), and 0.90 (CV 3.2%), respectively.

DiscussionTo the best of our knowledge, this is the first study

investigating the value of a new TDI derived index, E/(ES) to predict cardiac death in patients with HF, in sinus rhythm. E/(ES) ratio at hospital discharge was the strongest predictor of cardiovascular death when compared to several other echocardiographic parameters, coronary artery disease, NYHA functional class and plasmatic NTproBNP levels.

The clinical importance of predicting cardiac death in patients with LV dysfunction has been increasing. Several previous studies with echocardiographic imaging have suggested that LVEF20, LV volumes indices20 and LA size4,21 are strong predictors of outcome in the setting of congestive HF. In our study, LVEF, predictor of outcome on univariate analysis, was eliminated on multivariate analysis. Although indexed LA volume seemed to be a valuable echocardiographic parameter for prediction of cardiovascular death, E/(ES) was a better predictor in our patients.

TDI is now widely available on echocardiographic equipment of various manufacturers and is increasingly used in clinical practice but the relative importance of different

Figure 1 - The receiver-opera

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