Nghiên cứu biến đổi hình thái tim, áp lực động mạch phổi và NT proBNP huyết tương ở bệnh nhân tim bẩm sinh có luồng thông trái phải trước và sau can thiệp TT TIENG ANH

MINISTRY OF EDUCATION MINISTRY OF DEFENSE AND TRAINING MILITARY MEDICAL ACADEMY TRAN VAN PHU STUDY ON CHANGES OF HEART MORPHOLOGY, PULMONARY ARTERY PRESSURE AND PLASMA NT-proBNP IN CONGENITAL HEART DISEASES PATIENTS WITH LEFT TO RIGHT SHUNT BEFORE AND AFTER TRANSCATHETER CLOSURE Speciality: Internal medicine Code: 9720107 SUMMARY OF PHD DISSERTATION HA NOI - 2021 THIS THESIS WAS COMPLETED AT MILITARY MEDICAL ACADEMY Scientific supervisor: Associate Professor PhD Nguyen Lan Hieu Associate Professor PhD Pham Van Tran Reviewer 1: Do Doan Loi Prof MD., PhD Reviewer 2: Pham Thien Ngoc Assoc Prof MD., PhD Reviewer 3: Nguyen Oanh Oanh Assoc Prof MD., PhD The thesis will be examined and assessed by termination Council at: hour date month year It can be found at: National Library The Library of Military Medical Academy INTRODUCTION Congenital heart diseases with an incidence of about 1% in infants is the leading cause of infant and child mortality and a growing burden of disease for their family, health system and society Among congenital heart diseases, the group of congenital heart diseases with left to right shunt is the most common pathology This is also a group of heart diseases that can be completely cured by interventional cardiac catheterization or surgical closure of the catheter if diagnosed early Despite the advancement of science and technology and investment in equipment, the diagnosis of congenital heart diseases, as well as the monitoring of treatment, is not always perfectly determined by echocardiography and cardiac catheterization always possible, especially in lower level medical facilities NT-proBNP is an endogenous biomarker produced by pressure overload and cardiac chamber volume and is a sensitive and specific indicator of cardiac function Measurement of NT-proBNP levels is increasingly used to aid in the diagnosis, assessment of prognosis, and appropriate treatment in people with congestive heart failure NT-proBNP may also be useful in other conditions such as hypertrophic cardiomyopathy, myocardial infarction, or congenital heart diseases Studies around the world have proven that plasma NT-proBNP concentrations increase higher than in people with congenital heart diseases and are related to pulmonary artery pressure and the ratio of Qp/Qs In Vietnam, this biomarker has been studied and applied in clinical practice, including some types of congenital heart diseases, but there has been no study on NT-proBNP concentration and its relationship with cardiac morphological characteristics and pulmonary artery pressure Therefore, we conducted the study: "Study on changes in heart morphology, pulmonary artery pressure and plasma NT-proBNP in congenital heart patients with left to right shunt before and after intervention" with two objectives of the study: Study on changes in heart morphology, pulmonary artery pressure and plasma NT-proBNP in congenital heart diseases patients with left to right shunt before and after treatment 24 hours and three months The relationship of NT-proBNP with cardiac morphological characteristics, pulmonary artery pressure and Qp/Qs The thesis consists of 121 pages with including main chapters: - Introduction: pages - Chapter Literature overview: 32 pages - Chapter Subjects and methods: 22 pages - Chapter Results: 24 pages - Chapter Discussion: 35 pages - Conclusions and recommendations: pages - There were 40 tables, 10 illustrations and charts - Two articles related to the thesis have been published - There were 151 references with in Vietnamese documents and the rest were English documents Chapter LITERATURE OVERVIEW 1.1 Classification of congenital heart diseases The congenital heart diseases can occur in the heart chambers, heart valves or blood vessels, and the patient may have only one or more congenital heart defects The morphology of congenital heart diseases lesions ranges from simple to complex There are many different classifications of congenital heart diseases: Purple and non-violet congenital heart diseases; congenital heart diseases in children and adults; congenital heart diseases disease has left to right shunting, right to left shunt, and obstructive congenital heart diseases and valvular regurgitation injury 1.1.1 Congenital heart diseases disease with left to right shunt In this group, it is common to see atrial septal defect, ventricular septal defect and patent ductus arteriosus Less common are the aortopulmonary windows, partial atrioventricular canals and right atrial septal defects Clinically common atrial septal defect, ventricular septal defect and patent ductus arteriosus account for about 85% of all congenital heart diseases seen in children and almost all in adults Atrial septal defect is a congenital heart disease caused by a defect in the septum of the two atria This is a common congenital pathology, accounting for about 25% of congenital heart disease cases in children Ventricular septal defect alone is the most common congenital heart disease, accounting for about 37% of all congenital hearts in children The rate of patent ductus arteriosus reported in full term newborn is in 2,000 births, accounting for 5% - 10% of all congenital heart diseases 1.1.2 Congenital heart diseases with right to left shunt Characteristic of this group of diseases is often purple 1.1.3 Obstructive congenital heart diseases and valvular regurgitation injury Also called congenital heart diseases group without shunt These patients have underdeveloped heart chambers or blocked large blood vessels, preventing blood flow to meet the needs of body tissues 1.2 Congenital heart diseases with left to right shunt 1.2.1 Morphological and hemodynamic changes Congenital heart diseases with left to right shunt is described when blood flows from the left atrium, left ventricle or aorta to the right atrium, right ventricle or pulmonary artery or its branches The importance of left to right shunt can be expressed by the ratio Qp/Qs The patients with congenital heart diseases with left to right which of them are Qp/Qs will be > 1.2.1.1 Atrial septal defect Because there are defect in the atrial septum so blood flows from the left atrium to the right atrium Chronic mass overload in the atrial septal defect also causes dilation of the entire pulmonary vascular Hypertrophy of the muscular layer between the pulmonary arteries and veins, although its extent is often masked by vascular dilation The magnitude of the left to right shunt in the atrial septal defect depends on the size of the shunt, the pressure between the two ventricles, and the relative pulmonary and systemic vascular The left to right shunt is the cause of volume overload and morphological changes of right ventricle, right atrium, left atrium and pulmonary circulation However pulmonary arterial pressure was only slightly increased and in most patients, pulmonary vascular resistance remained within the normal range in patients aged months 1.2.1.2 Ventricular septal defect With ventricular septal defect, the blood flows from the left ventricle through the right ventricle into the pulmonary artery The right and left ventricles contract simultaneously, the right ventricle does not recognize the overloaded volume in this situation The right atrium also failed to recognize a mass overload However the pulmonary artery receives increased blood volume Lesions in the ventricular septal defect allow blood from the systemic circulation to pass through the pulmonary circulation, shifting the flow from an area of high pressure to an area of low pressure (from left to right ventricle) In general, the ventricular septal defect leaves two main consequences on the heart: (i) Gradual change in the pulmonary arteriole system by increasing pulmonary artery flow (ii) Overloading the left heart Morphological changes of left ventricle and left atrium If the ventricular septal defect is small, the right ventricular pressure and pulmonary artery pressure increase insignificantly Conversely, if the ventricular septal defect is wide then the high right ventricular pressure can equal the left ventricular pressure The consequences in the lungs depend on the response of the pulmonary vasculature to increased blood flow, affecting the capacity and elasticity of the pulmonary circulation The resistance of the pulmonary vasculature is also an important factor determining the shunt 1.2.1.3 Patent ductus arteriosus When in the patent ductus arteriosus then the blood flows from the aorta to the pulmonary artery so the pulmonary artery, the left atrium, and the left ventricle are overloaded, but the right atrium and right ventricle are not Consequences causing changes in left heart morphology Due to the presence of coronary artery and more blood flows through the pulmonary artery cause increasing the pressure in the pulmonary circulation 1.2.2 Natural progression 1.2.2.1 Natural progression of atrial septal defect Spontaneous progression of atrial septal defect is relatively benign except for large fistulas and the patient with other associated cardiac defects Typically, the patient with atrial septal defect remain physically active and non symptom in the childhood, and many patients whom have survived and even average sized atrial septal defect by age 40 before the symptoms develop Secondary atrial septal defect may close spontaneously or remain open Sometimes it is enlarge 1.2.2.2 Natural progression of ventricular septal defect The natural progression of ventricular septal defect ranges from spontaneous closure of the shunt to congestive heart failure and death in the childhood Spontaneous closure of the fistula usually occurs in children younger than years of age However it is uncommon after the age of years 1.2.2.3 Natural progression of patent ductus arteriosus Risks associated with long term of patent ductus arteriosus include endocarditis, patent ductal arteriosus calcification, patent ductal arteriosus aneurysm or enlargement, heart failure and pulmonary hypertension 1.3 NT-proBNP NT-proBNP is a cardiac biomarker secreted primarily from cardiac ventricular myocytes in response to increased volume and chamber pressure Elongated cardiomyocytes are the main stimulator for the secretion of NT-proBNP into the blood Clinically, the value of NT-proBNP is used in the diagnosis of left ventricular systolic and diastolic dysfunction and prognosis which are including heart failure, acute coronary syndromes, stable coronary artery disease and stable angina NT-proBNP may also be useful in other settings such as hypertrophic cardiomyopathy, right ventricular dysplasia, or congenital heart diseases BNP was approved for use by the FDA in 2001 and NT-proBNP in 2002 as a marker for cardiac dysfunction NT-proBNP does not indicate specific heart disease, but elevated test results indicate the presence of underlying cardiac dysfunction Normal plasma NT-proBNP levels are unlikely to include cardiac dysfunction The high plasma NT-proBNP levels, even in the clinical setting of undiagnosed cardiovascular disease, are predictive of future cardiovascular events Chapter SUBJECTS AND METHODS 2.1 Subjects The patients with a definitive diagnosis of congenital heart diseases with left to right shunt such as: Atrial septal defect, ventricular septal defect and patent ductus arteriosus There are indications to close the shunt by intervention The study was conducted at Bach Mai hospital from March 2015 to September 2017 Including 190 congenital heart diseases with left to right shunt such as: Atrial septal defect, ventricular septal defect and patent ductus arteriosus 107 healthy people 2.2 Methods 2.2.1 Design Described cross sectional study with before and after comparison Using a group of healthy people to compare indicators related to the concentration of NT-proBNP levels Selected random and convenient sample 2.2.3 Steps and variables - The study patients were collected data, before and after cardiac catheterization 24 hours and reexamination after months - Clinical and paraclinical: + Age and gender ( 60 years old) + Described clinical characteristics: chest pain, dyspnea, palpitations, hemoptysis, edema, hepatomegaly + Described electrocardiographic characteristics: electrocardiographic axis and heart rhythm - Described cardiac morphology and echocardiography: + Atrial septal defect, ventricular septal defect and patent ductus arteriosus, congenital heart diseases others + Right ventricular diameter, aortic diameter, Dd, Ds, FS, EF, interventricular septum thickness, left ventricular posterior wall thickness, size of shunt, size and pressure of pulmonary artery + Pulmonary pressure is divided into three levels: normal pulmonary pressure: < 30 mmHg; mild to moderate increase 30-59 mmHg and severe increase ≥ 60 mmHg - Cardiac chamber and vascular variables measured by cardiac catheterization: size of shunt, pulmonary artery pressure, Qp/Qs + Based on the influence of catheter flow on pulmonary artery hemodynamics, the size of the catheter is divided into two types: large and small: for patients with atrial septal defect, the size < 20 mm is small, the rest is large; for patients with ventricular septal defect, the size < 10 mm is small and for patient with patent ductus arteriosus, the size is mm + Qp/Qs is divided into levels: < 1.5 was small shunt; between 1.5-2 was medium shunt and >2 was high shunt - Test variables of plasma NT-proBNP: NT-proBNP is calculated in units of pg/ml 2.2.5 Methods of information collection The patient is allowed to make a study record, the PhD student directly asked the patient, clinical examinated and entered data Facilities: testing machine, echocardiogram machine and cardiac catheterization system 2.2.6 Data processing and analysis - Data processing in the study used SPSS software version 22.0 - Used logistic regression to analyze the correlation between dependent variable and influencing factors that are independent variables (qualitative or quantitative) To eliminate confounding factors, we consider univariate logistic correlation between each factor with treatment outcome and which factors are not significant (p > 0.05) Then consider the multivariable logistic correlation and remove the non-significant factors (p > 0.05) 2.2.7 Ethical issues in study - Approved by the board of the Military Medical Academy - The study was approved by Bach Mai Hospital - Patient's family agrees to participate - The treatment regimens and treatment results were not changed Chapter RESULTS 3.1 General characteristics of the study subjects 3.1.1 Age and sex characteristics A total of 190 patients and 107 normal people were recruited into the study The age of study group was < 16 (45; 23.7%); 16-40 (86; 45.30%); 10 41-60 (47; 24.70%) and > 60 (12; 6.3%) There were not different from the control group The mean age of patients with atrial septal defect, ventricular septal defect and patent ductus arteriosus were: 41.31 ± 15.82, respectively; 21.58 ± 13.52; 21.74 ± 17.84 years old Male 62 (32.6%), female 128 (67.4%) 3.1.2 Characteristics of the distribution of patients Atrial septal defect 88 (46.3%), ventricular septal defect 60 (31.6%), and patent ductus arteriosus 42 (22.1%) Patients with symptoms such as exertional dyspnea, palpitations, etc., should been stable treatment before cardiac catheterization 2-3 days 3.2 Cardiac morphology, pulmonary artery pressure, plasma NTproBNP concentration and Qp/Qs ratio 3.2.1 Cardiac morphology and left ventricular systolic function Table 3.1 Echocardiographic parameters before and after closing of shunt with atrial septal defect Before 24 After 24 After hours hours months p Parameters Mean±SD(n=88 ) Mean±SD(n=8 8) Mean±SD(n=3 5) RV (mm) 31.06 ± 5.89 26.32 ± 4.46 25.93 ± 3.63 PA (mm) 28.18 ± 5.80 25.38 ± 5.21 24.69 ± 3.19 Dd (mm) 3.75 ± 4.28 37.49 ± 4.56 37.57 ± 4.19 Ds (mm) 24.49 ± 3.48 22.10 ± 3.59 23.64 ± 3.06 FS (%) 37.89 ± 5.62 40.61 ± 5.75 37.91 ± 6.05 EF (%) 68.56 ± 6.73 70,74 ± 8.14 69.16 ± 4.79 0.05* >0.05; >0.05* *Comparison before closing the shunt after 24 hours and follow-up months After closing atrial septal defect 24 hours, right ventricular diameter was smaller than before closing (p < 0.01); The pulmonary artery origin and the left ventricular dimensions smaller than before closure but with p > 0.05) At months after closing th shunt, the right ventricular and 14 Median (Q1Q3) Median (Q1Q3) ASD (n=88) 70.79 (43.51 – 214.94) 87.15 (57.51 – 242.46) VSD (n=60) PDA (n=42) 50.53 (21.78 – 108.38) 50.99 (28.67 – 144.02) 60.51 (31.80 – 151.13) 57.43 (32.83 – 79.69) 53.70 (24.48 – 82.38) 63.31 (43.32 – 180.51) Total (n=74) Median (Q1Q3) 61.07 (29.46 – 102.97) 30.96 (19.55 – 37.77) 29.67 (15.92 – 40.64) 36.57 (23.10 - 74.99) >0.05 0.05 0.05 0.05 0.05) But at the time after months, the concentration of NT-proBNP decreased compared to before closing the shunt with statistical significance (p < 0.01) Relationship between plasma NT-proBNP concentration with some cardiac morphological characteristics, pulmonary artery pressure and Qp/Qs ratio - The concentration of NT-proBNP was positively correlated with right ventricular size, pulmonary artery size, left ventricular size and shunt size - The concentration of NT-proBNP plasma was positive correlation with systolic pulmonary artery pressure - The concentration of NT-proBNP plasma was weak positive correlation with Qp / Qs - The cutoff of NT-proBNP was 126.4 pg/ml, sensitivity 94.6% and specificity 72% corresponding to systolic pulmonary arterial pressure ≥ 60mmHg - The concentration of NT-proBNP of patients with Qp / Qs > was significantly higher than that of patients with Qp / Qs ≤ (p < 0.01) The cutoff of NT-proBNP was 127.4 pg/ml, sensitivity 82.2% and specificity 74.4% 27 RECOMMENDATIONS The NT-proBNP test is relatively inexpensive, noninvasive, rapid, and a commonly used cardiac biomarker The present study shows that plasma NT-proBNP can provide a useful clinical tool in the diagnosis and monitoring of congenital heart diseases with left to right shunt Especially in the conditions of Vietnam, the ultrasound of congenital heart diseases is not performed accurately by any medical facility and cardiac catheterization is not always feasible This finding warrants further studies in larger groups and highlights the potential of NT-proBNP to contribute to the diagnosis and monitoring of congenital heart diseases in general and congenital heart diseases with left to right shunt in particular PUBLISHED SCIENTIFIC PAPERS RELATED TO THE CURRENT THESIS Tran Văn Phu, Luu Minh Quang, Nguyen Lan Hieu, et al (2020) Relationship between plasma NT-proBNP levels with some echocardiographic parameters and cardiac catheterization in patients with left to right shunt Vietnam Medical Journal., 445(1): 45 – 50 Tran Văn Phu, Luu Minh Quang, Nguyen Lan Hieu, et al (2020) Some morphological and hemodynamic characteristics and plasma NTproBNP level in congenital heart disease patients with left to right shunt Journal of Military Pharmaco-Medicine., 45(6): 41 – 47 ... than that of control group (p < 0.01) The plasma NT- proBNP concentration of each patient group was higher than NT- proBNP of control group (p < 0.01) Table 3.6 Plasma NT- proBNP concentration before... the sizi of shunt The plasma NT- proBNP concentration increased in patients with large shunt, the difference was statistically significant (p < 0.01) The plasma NT- proBNP concentration positive... large and small shunts, the difference in plasma NT- proBNP concentration was not statistically significant even though the NT- proBNP concentration of the patients with large shunts were higher (p