MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH
HO CHI MINH CITY UNIVERSITY OF MEDICINE AND PHARMACY
NGUYEN DUC KHANH
PROGNOSIS ROLE OF
sST2 BIOMARKER IN HEART FAILURE
DOCTORAL THESIS IN MEDICINE
HO CHI MINH CITY, 2022
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH
HO CHI MINH CITY UNIVERSITY OF MEDICINE AND PHARMACY
NGUYEN DUC KHANH
PROGNOSIS ROLE OF
sST2 BIOMARKER IN HEART FAILURE
INDUSTRY: INTERNAL CARDIOLOGY CODE: 62720141
DOCTORAL THESIS IN MEDICINE
SCIENTIFIC INSTRUCTOR:
1. PROFESSOR, DR. DANG VAN PHUOC
2. Dr. LE THANH LIEM
HO CHI MINH CITY, 2022
COMMITMENT
I hereby certify that this is my own research work, the research results presented in the thesis are honest, objective and have never been published anywhere.
Thesis author
Nguyen Duc Khanh
INDEX
LIST OF ENGLISH AND VIETNAMESE ABBREVIATIONS AND TERMS i
LIST OF TABLES iv
LIST OF CHARTS vii
LIST OF DIAGRAM ix
LIST OF FIGURES x
INTRODUCTION 1
Chapter 1. OVERVIEW 4
1.1. Overview of chronic heart failure 4
1.2 The role of biomarkers in the prognosis of chronic heart failure 13
1.3 Overview of the IL-33/ST2 axis and soluble ST2 17
1.4 Studies of sST2 in chronic heart failure 27
Chapter 2. RESEARCH OBJECTS AND METHODS 36
2.1. Research design 36
2.2. Research subjects 36
2.3. Time and place of research 37
2.4. Sample size of the study 37
2.5. Identify independent and dependent variables 38
2.6. Methods and tools for measurement and data collection 49
2.7. Research process 54
2.8. Data analysis method 55
2.9. Ethics in research 57
Chapter 3. RESULTS 58
3.1 Survey of research population characteristics 59
3.2 Survey on concentration, distribution and characteristics of sST2 67
3.3 Survey of the relationship between sST2 and clinical, paraclinical and
Treatment characteristics in chronic heart failure 69
3.4 Survey of the prognostic role of sST2 in chronic heart failure 74
Chapter 4. DISCUSSION 90
4.1 Characteristics of the study population 90
4.2 Concentration, distribution and characteristics of sST2 103
4.3 Relationship between sST2 and clinical and paraclinical factors in heart failure
................................................................ ................................................................ .........105
4.4 Prognostic role of sST2 in heart failure hospitalization, cardiovascular death and all-cause mortality 113
TOPIC RESTRICTIONS 125
CONCLUSION 126
PROPOSAL 128
LIST OF RELATED PUBLISHED WORKS 129
REFERENCES APPENDIX
APPENDIX 1. Consent form for participation in the study APPENDIX 2 Data collection table
APPENDIX 3. sST2 testing procedure
APPENDIX 4. Functional symptoms, physical symptoms, causes and classification of chronic heart failure according to the European Society of Cardiology 2016
APPENDIX 5. Heart failure treatment regimen of Cho Ray Hospital and Recommendations for diagnosis and treatment of heart failure of the Vietnam Cardiology Association
APPENDIX 6. Decision of the Medical Ethics Council APPENDIX 7. List of research patients
LIST OF ABBREVIATIONS AND TERMS ENGLISH AND VIETNAMESE
Acronym
English | Vietnamese | |
BCTGN | Dilated cardiomyopathy | |
BPTNMT | Chronic obstructive pulmonary disease | |
BTBS | Congenital heart disease | |
BVT | Valvular heart disease | |
CTTA | Angiotensin receptor blocker | |
DKA | Aldosterone receptor antagonist | |
Condition | Left ventricular end-diastolic diameter | |
collect | ||
Prime Minister | Left ventricular end-diastolic diameter | |
Truong | ||
Condition | Left atrial diameter | |
DLC | Standard deviation | |
DLCTDD | Estimated glomerular filtration rate | |
Mobile | Diabetes | |
HCMVMT | Chronic coronary syndrome | |
HTL | Smoking | |
KTC | Confidence interval | |
NMCT | Myocardial infarction | |
PSTM | Ejection fraction | |
PSTMTT | Left ventricular ejection fraction | |
EXCUSE | Hypertension | |
TTTTTTh | Left ventricular end-systolic volume | |
TTTTTTg | Left ventricular end-systolic volume | |
Truong |
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TV-MNN Death from all causes
TV-TM Cardiovascular Death
TK-GC Sympathetic Nerve
UCMC ACE inhibitor
ACC American College of Cardiology AHA American Heart Association American Heart Association
AIC Akaike Information Criteria Akaike Information Criteria ANP Atrial-type natriuretic peptide AUC Area Under Curve Area under the curve BIC Bayes information criteria Bayes information criteria BMI Body Mass Index Body mass index
BNP B-type natriuretic peptide BUN Blood Ure Nitrogen Blood Urea Nitrogen
CABG Coronary artery bypass graft
surgery
Coronary artery bypass grafting
CKMB Creatine Kinase – MB CKMB
Cre Creatinine Blood creatinine
CRP C-reactive protein C-reactive protein
cTn Cardiac troponin Cardiac troponin
EF Ejection Fraction
ELISA Enzyme linked immunosorbent
assay
Enzyme-linked immunosorbent assay
ESC European Society of Cardiology
GDF-15 Growth differentiation factor-15 Growth differentiation factor 15 HDL High density Lipoprotein High density Lipoprotein
HFpEF Heart Failure With Preserved Ejection Fraction
Heart failure with preserved ejection fraction
HFrEF Heart Failure With Reduced
Ejection Fraction HFmrEF Heart Failure With Mid-
Range Ejection Fraction
Heart failure with reduced ejection fraction
Heart failure with mildly reduced ejection fraction
HR Hazard Ratio Hazard Ratio
Hs- Tn T High sensitivity Troponin T High sensitivity Troponin T IL Interleukin Interleukin
Ig Immunoglobulin Immunoglobulin
LDL Low density Lipoprotein Low density Lipoprotein
NHANES National Health and Nutrition
Examination Survey NOS/ROS Nitric oxide synthase/reactive
oxygen species
National Health and Nutrition Examination Survey
NO synthase/reactive oxygen molecules
NT-proBNP N-terminal pro-hormone BNP N-terminal pro-hormone BNP precursor NYHA New York Heart Association New York Heart Association
Pro-ANF Pro-Atrial Natriuretic Factor Pro-Atrial Natriuretic Factor
RAS Renin_Angiotensin System Renin-Angotensin System
ROC Receiver Operating Characteristic Curve
ST2 Supperssion of Tumorigenicity gene 2
ROC curve
Oncogenic suppressor gene 2
sST2 Soluble isoform of ST 2 ST2 soluble form ST2L Transmembrane isoform of ST2 ST2 transmembrane form WHO World Health Organization World Health Organization