MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN THITHANH TRUNG STUDY OF CLINICAL CHARACTERISTICS AND LEFT VENTRICULAR DYSSYNCHRONY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION USING GATED-SPECT IMAGING Specialty: INTERNAL CARDIOVASCULAR CODE: 62.72.01.41 DOCTOR DISSERTATION Ha Noi - 2020 THIS DISSERTATION WAS COMPLETED AT 108 INTSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Scientific supervisors: Associate Professor Dr.Le Ngoc Ha Associate Professor Dr Pham Thai Giang Reviewers: Associate Professor Dr Dinh Thi Thu Huong Associate Professor Dr Luong Cong Thuc Associate Professor Dr Tran Van Riep The dissertation was examined and assessed by Institutional Scientific Council at 108 Institute of Clinical medical and Pharmaceutical sciences at on , The disse rtation can be found at: National Library Library of 108 Institute Pharmaceutical sciences of Clinical medical and INTRODUCTION Necessity of the study Left ventricular dyssynchrony is one of the consequences of coronary artery disease After early myocardial infarction, 56.0% and 61.0% of patients had left ventricular dyssynchrony based on evaluation of Tissue Doppler Imaging According to Ko (2009), the rate of patients with left ventricular dyssynchrony after myocardial infarction is generally 32.6% Left ventricular dyssynchrony is close ly associated with heart failure,increasing major adverse cardiovascular events (MACE) as well as mortality in patients after myocardial infarction Following 197 patients with myocardial infarction, Pazhenkottil (2011) showed that the rate of patients with MACE in the group with left ventricular dyssynchrony was much higher than that in the group without left ventricular dyssynchrony (62.9% compared with 24.7%) and proved that left ventricular dyssynchrony is one of the three independent predictors of MACE There have been many methods for assessing left ventricular dyssynchrony such as: electrocardiogram, Tissue Doppler ultrasound of cardiac muscle tissue, 3D ultrasound, and myocardial perfusion scan, etc in which myocardial perfusion imaging proved to be superior in assessing left ventricular dyssynchrony by its accuracy and objectivity In Vietnam, some studies have applied Gated-SPECT to evaluate residual myocardial ischemia, myocardial infarction scars, cardiac wall motion and cardiac function Several domestic studies published on the use of electrocardiography, Tissue Doppler ultrasound in evaluating left ventricular dyssynchrony However, there have not been any studies to assess the dyssynchrony performed with myocardial perfusion scan by Gated-SPECT method with specialized software for analyzing left ventricular dyssynchronyin patients after myocardial infarction Therefore, the study of this issue is controvers ial, scientific and brings about a lot of benefits for physicians in the prognosis and treatment of patients after myocardial infarction Meanings of the study The use of myocardial perfusion imaging (MPI) in assessing left ventricular dyssynchrony will help overcome some disadvantages of Tissue Doppler ultrasound methods For example, MPI could assess 17 myocardial regions simultaneously including the cardiac apex, whereas the Tissue Doppler ultrasound can not assess the dyssynchrony at the heart apex region, and this method has an increase in the unit This method of MIP, using degrees to assess, also corrects errors when evaluating patients with different heart rates In addition, MPI also assesses the status of residual myocardial ischemia, cardiac wall motion, heart function, cardiac muscle survival status Therefore this method helps clinicians predict and offer better treatments for patients Objectives of the study To investigate some clinical, laboratory characteristics and left ventricular dyssynchrony using Gated-SPECT imaging in patients after acute myocardial infartion To assess the relationship between left ventricular dyssynchrony on Gated-SPECT imaging and some clinical features, echocardiography in patients after acute myocardial infarction Structure of the disse rtation The dissertation consists of 128 pages (excluding references and indexes) including main chapters: Introduction: 02 pages, Chapter – Literature review: 36 pages, Chapter - Subjects and methodology: 19 pages, Chapter –Research results: 32 pages, Chapter - Discussions: 32 pages, Conclusion and recommendations: 03 pages The dissertation has 29 tables, 13 schemes and figures, 20 illustration, 157 references with 17 in Vietnamese and140 in English CHAPTER I: LITERATURE REVIEW 1.1 Les ions after myocardial infarction Myocardial infarction (MI) is a condition when atherosclerosis blocks the coronary arteries, stop supply of blood and oxygen to the heart muscle Although there have been many advances in diagnosis, treatment and monitoring, myocardial infarction remains a challenging issue for the health sector The more patients rescued from acute myocardial infarction, the more patients have to accompany the post-MI disorders such as residual myocardial ischemia, left ventricular remodelling, left ventricular dyssynchrony, arrhythmia, heart failure, reinfarction 1.2.Cardiac dysynchrony In cardiology, dyssynchrony is the phenomenon in which the different parts of the heart contract in a non-rhythmic physiological sequence, leading to a decrease in ejection efficiency.Left ventricular mechanical dyssynchrony is the differences in the timing of contraction or relaxation between different myocardial segments or the contraction of the heart muscle areas that are delayed in the systole.Mechanical dyssynchronyusually appears in the late stages of some heart conditions, associated with hypertrophy and left ventricular dysfunction Left ventricular mechanical dyssynchrony is particularly common after myocardial infarction Left ventricular dyssynchronyreduces the ejection fraction, aggravates heart failure, and increases myocardial oxygen demand, increases left ventricular remodelling The detection of left ventricular dyssynchrony also plays an important role in the designation and prognosis of the treatment success of resynchrony 1.2.1 Methods for evaluating left ventricular dyssynchrony  Routine ECG This method is simple, easy to implement and can be implemented in all health facilities However, it is only possible to assess the electrical dyssynchrony and does not reflect the mechanical dyssynchrony According to the North American Heartbeat Association and the American Society of Echocardiography when PR≥160 ms, QRS≥120 ms is considered to have electrical dyssynchrony and this is a criterion for the selection of patients after MI designated as cardiac resynchronization therapy (CRT)  M-mode echocardiography This method can only assess the dyssynchrony of the ventricular septum and left posterior ventricle by measuring the maximum difference in time of inoculation of the ventricular septum and left posterior ventricular wall When this index is ≥130 ms, it is an indicator to evaluate intraventricular dyssynchrony  Tissue Doppler imaging  Pulse-Doppler Ultrasound: This method assesses by measuring the time interval Ts is the time from the beginning of the QRS complex to the start of the S wave or to the S wave peak of each region, then based on the difference in Ts of the myocardial regions, it will evaluate th level of left ventricular dyssynchrony If the Ts difference between the wall and lateral wall is>65 ms, there is a left ventricular dyssynchrony  Ultrasound Tissue velocity imaging (TVI):In this method, each cross section will assess simultaneously the movement of two or more cardiac muscle regions in the same cycle By visual observation, the time when the peak velocity of two regions overlap or close to each other is considered as the opposite two regions contracting synchronously and vice versa  Tissue synchronization imaging (TSI):The ultrasound can automatically calculate the time difference to reach the maximum systolic wave velocity of the opposite myocardial regions and the 12 myocardial regions as well as the standard deviation of the time to reach the maximum systolic wave velocity of 12 cardiac muscle regions (Ts - SD) on basic dimentionals and calculate the maximum time difference of any two cardiac muscle regions According to Yu,that Ts-SD> 34.4 ms and Ts - Diff> 105 ms were significant in predicting left ventricular remodelling  There are also other more modern methods on ultrasound such as:3D Ultrasound Marker, Real-time 3D Ultrasound Imaging These methods are expensive but overcome the limitations of the above ultrasound methods 1.3 Left ventricular dyssynchrony assessed by Gated myocardial perfusion SPECT Principle: each cardiac cycle is divided into sections (usually or 16 sections) of equal duration referred to as “frames” The system records the highest radioactivity count on the perfusion image of each myocardial region through theframes (or sections in a cycle) The left ventricle is divided into more than 600 regions, each containing information about the radioactive counts for each section Information obtained from these 600 regions in a section is represented as polar maps That is the view of the transverse section of the myocardial axis with the center is the cardiac apex and the border is the base of the heart.From the radiologica l data that "each region" cardiac muscle varies by phases, which are “harmonic” in nature, the software automatica lly uses the Fourier function to estimate the change in thickness of each region according to the heart cycle duration These are expressed as a sinusoidal graph, and help find out when the region's cardiac musc le begins to contract, which are called the onset of mechanical contraction (OMC).600 different cardiac muscle regions will have 600 OMC moments respectively The software, then, converts these 600 data into a color-coded polarized map called (phase polar map) with the center being the heart apex and the periphery being the heart's bottom Visually, the picture shows the slow contraction of the heart muscle (light area) The software also automatically calculates PSD which is the standard deviation of the OMC phase distribution of more than 600 cardiac muscle regions Normally, the heart muscle regions contract in sync, that is, their OMCs are close together The OMC set of these 600 cardiac muscle regions will be close to each other, the graph has a uniform distribution with a low standard deviation of the OMC phase distribution (PSD) The larger the PSD, the more different the OMC of myocardial regions are, the more uneven the distribution of OMCs is, the more severe the degree of dyssynchrony.Normally, when the heart muscle regions have synchronized contractions, the OMC of 600 myocardial regions will be close to each other, creating a chart with a high shape, narrow legs, a normal distribution with a deviation index (Skewness index) close to and the oblique index (Kurtosis index) is close to In case of dyssynchrony, OMC of different areas are far from each other and the chart will be low with wide legs To measure the oscillation level of OMC between more than 600 regions, the HBW (Histogram bandwidth) is used as the interval during which 95% of the myocardial muscle regions begin to contract or the interval containing 95% of the OMC score 1.4 Studies using Gated-SPECT to evaluate left ventricular dyssynchrony 1.4.1 International studies Trimble et al (2006) studied a group of 120 patients with left ventricular dysfunction, 33 patients with a left bundle branch block, 19 patients with a right bundle branch block and 23 patients with a pacemaker, compared with 157 healthy subjects in the control group showed that the average phase standard deviation (PSD) and histogram bandwidth(HBW) of normal people were 15.7 ± 11.8 and 42.0 ± 28.4, with Skewness and Kurtosis indices of 4.6 ± 2.4 and 22.4 ± 11.7, respectively The study a lso showed a clear difference in these indicators among patients with left ventricular dysfunction, left bundle branch block and those in the control group Zafrir (2013) studied 787 patients after MI, with an average of 18.3 ± 6.2 months, showing that the PSD index on GSPECT was significant for predicting mortality in general and cardiovascular death in particular Santiago Aguade et al (2016) studied 408 patients (150 control groups and disease groups) to find the cut off index to distinguish the group with dyssynchrony and the normal group with PSD> 18.4º, HBW> 51º, Skewness ≤ 3.2º, Kurtosis ≤ 9.3º The study a lso proves the value of those four indicators in identifying whether a patient has been identified with cardiac resynchronization therapy(CRT) or not 1.4.2 Vietnamese studies Quyen Dang Tuyen (2010) studied left ventricular dyssynchrony in patients with heart failure by Tissue Doppler ultrasound showed that the heart failure group had a higher rate and level of dyssynchrony than the control group and there is a correlation between the degree of dyssynchrony on Tissue Doppler ultrasound with dyspnea level, QRS width and e jection fraction Mai Hong Son, Le Ngoc Ha (2014) studied 50 patients with coronary artery disease and 30 patients without coronary artery disease in the control group using GSPECT Results showed that the dyssynchrony indexes of HBW and PSD in the disease group were significantly higher than those in the control group and there was a correlation between the dyssynchrony index and the width of defect area and ejection fraction Summary of some findings of left ventricular dyssynchrony in patients after myocardial infarction and some existing problems Gated-SPECT is an effective tool in the diagnosisof dyssynchrony Dyssynchrony indices on Gated-SPECT have good prognosis for MACE and mortality in patients after acute myocardial infarction In Vietnam, there has not been much research on left ventricular dyssynchronyby Gated-SPECT and no research has evaluated the relationship between dyssynchrony on Gate d-SPECT a nd clinica l a nd ultrasonic synchronous Tissue Doppler imaging CHAPTER RESEARCH SUBJECTS AND METHODOLOGY 2.1 Research subjects The study was carried out at 108 Military Central Hospital from October 2014 to December 2018, on a case group of 106 patients after myocardial infarction and the control group of 34 subjects without cardiovascular diseases  Patient selection criteria: Case group Having been diagnosed with acute MI (according to World Health Organization standards - 2012) that have passed the acute phase for at least 14 days Stable clinical condition, hemodynamics, cardiac enzyme tests returned to normal Meeting the criteria for Gated-SPECT imaging according to the guidelines of the American Society of Nuclear Cardiology 2010 Control group No cardiovascular diseases when having clinical examination, normal results of ECG and echocardiography No evidence of myocardial ischemia on myocardial perfusion imaging: radiation defects in each region 70ml had significantly higher PSD and HBW values than the group with normal ESV (r =0.57, p