Nghiên cứu đặc điểm lâm sàng và tình trạng rối loạn đồng bộ thất trái ở bệnh nhân sau nhồi máu cơ tim bằng xạ hình gated SPECT tt tiếng anh

There have been many methods for assessing left ventricular dyssynchrony such as: electrocardiogram, Tissue Doppler ultrasound of cardiac muscle tissue, 3D ultrasound, and myocardial per

OF EDUCATION AND TRAINING 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

THIS DISSERTATION WAS COMPLETED AT

108 INTSTITUTE OF CLINICAL MEDICAL AND

PHARMACEUTICAL SCIENCES

Scie ntific supe rvisors:

1 Associate Professor Dr.Le Ngoc Ha

2 Associate Professor Dr Pham Thai Giang

Revie we rs:

1 Associate Professor Dr Dinh Thi Thu Huong

2 Associate Professor Dr Luong Cong Thuc

3 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:

1 National Library

2 Library of 108 Institute of Clinical medical and Pharmaceutical sciences

INTRODUCTION

1 Ne cessity 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

2 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

3 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

4 Structure of the disse rtation

The dissertation consists of 128 pages (excluding references and indexes) including 4 main chapters: Introduction: 02 pages, Chapter 1 –Literature review: 36 pages, Chapter 2 - Subjects and methodology: 19 pages, Chapter 3 –Research results: 32 pages, Chapter 4 - 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 afte r 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, re-infarction

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 le ft 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 3 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 Le ft ventricular dyssynchrony assessed by Gate d myocardial perfusion SPECT

Principle: each cardiac cycle is divided into sections (usually 8 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 informationabout 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 0 and the oblique index (Kurtosis index) is close to 3 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 Gate d-SPECT to evaluate le ft 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 2 RESEARCH SUBJECTS AND METHODOLOGY 2.1 Rese arch 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

- No branch block

by the American Society of Nuclear Cardiology

2.2 Methodology:

- This is a hospital-based, descriptive, cross-sectional case-control study

- Steps to conduct research:

+ All subjects were interviewed and had clinical examination

+ All subjects were assigned to have basic tests of: pulmonary X-ray, lead ECG, bas ic biochemical test, Cardiac Doppler ultrasound to record basic parameters ofcardiac structure and function including Dd, Ds, EDV, ESV, and EF

12-+ Parameters to evaluate left ventricular dyssynchrony on TSI according

to American Society of Echocardiography (2008):

When the standard deviation of time reaches the maximum speed of 12 regions in the systole Ts - SD 34.4 ms on TSI, patients have left ventricular dyssynchrony

The biggest difference of time to reach the maximum speed of

12 regional systolic is Ts-Diff and when Ts - Diff ≥ 105 ms on TSI, patients have left ventricular dyssynchrony

+ The patient had an Electrocardiographically gated myocardial perfusion SPECT to assess the position, degree of radiation injury, to calculate a summed rest score (SRS), summed stress score (SSS) and the difference between the two phases, to assess the viability of myocardial, structure index and cardiac function including Dd, Ds, EDV, ESV, EF and parameters to evaluate left ventricular dyssynchrony including standard deviation the onset of contraction in more than 600 left ventricular myocardial regions (PSD) andthe interval that 95% of the myocardial regions begin to contract (HBW)

The indices of evaluating left ventricular dyssynchrony on Gated-SPECT include:

- PSD: OMC standard deviation of myocardial regions (more than 600 OMC)

- HBW: interval containing 95% of OMC

- HK, HS: Histogram Kurtosus and skewness

Assessment of left ventricular dyssynchrony

- The control group had 4 indicators assessed with PSD, HBW, HK, and HS

- From the mean of PSD and HBW of the control group, we take the threshold of > +2SD of the control group as the threshold of dyssynchrony Thus, the criteria for assessing the dyssynchrony are when the PSD or HBW exceeds the + 2SD threshold of the control group

2.3.Data processing

Data were processed using STATA 14.2 software Quantitative variables are expressed as mean (X) and standard deviation (SD), median; Qualitative variables are expressed as percentages

2.4 Ethics in rese arch

The study did not violate ethica l regulations when carrying out biomedica l research

CHAPTER 3 RESEARCH RESULTS

The study was conducted on 140 subjects including the research group of

106 patients after MI and the control group of 34 people without cardiovascular diseases The study subjects were tracked down for at least 12 months after myocardial infarction in the period from October

2014 and December 2018

3.1 Clinical, laboratory characte ristics and le ft ve ntricular dyssynchrony using Gate d-SPECT in patie nts afte r MI

The mean age of bothrcase group and control group were quite high with 65.4 ± 10.31 and 62.68 ± 6.42, respectively The highest age in the research group is 81 years old and the lowest is 49 years old, in the control group the oldest is 79 years old and the youngest is 53 years old Men accounted for higher percentage in the research group w ith 83.96% and 16.04%, respectively, compared to 76.47% and 23.53% in the control group

The majority of patients had typical chest pain symptoms upon admission (53.8%), atypica l chest pain accounted for 44.3%, and those without pain was 1.9%.Patients were assessed of heart failure according

to New York Heart Association (NYHA) classification with mainly heart failure class II accounting for 52.8%, the rate of severe heart failure NYHA class III, IV was 30.3% The number of patients in the intervention of phase 1was a relatively high with 58.1%, those with medical treatment was 41.5% and only 0.95% was treated with coronary artery bypass surgery

The most common risk factors are hypertension (66.98%), dyslipidemia (28.3%), smoking (33.02%), obesity (26.42%) and diabetes (24.5%);

Among 106 patients after MI, 61 patients had early coronary intervention, accounting for 58.1%; 13 patients died during the 12-month follow-up, accounting for 12.26%

Inferior wall myocardial infarction accounted for the highest rate (41.51%), the anterior wall myocardial infarction accounted for 38.68%, mainly the large anterior MI with 17.92% The prevalence ò those with combined MI was 7.55% and the prevalence of patients with Non-Q wave MI was 8.49% 6 patients after the MI had wide QRS complex of >

120 ms accounting for 5.7% The prevalence of those with left branch block was 5.7%

The mean index of left ventricular systolic volume in the disease group after MI is larger than that of the control group with 59.4 ± 31.03; 30.6 ± 4.65, respectively The average index of left ventricular systolic function in the disease group after MI is lower than that of the control group w ith 46.8 ± 14.25; 66.6 ± 5.33, respectively

On Tissue Doppler imaging (TDI), the average indices of the standard deviation of time reaches a maximum speed of 12 regions in the systole Ts - SD12 and the largest difference in time reaches the maximum speed of 12 systolic regions Ts - Diff12 are 43.2 ± 22.19; 121.8 ± 49.81, respectively Of which 60 patients had Ts - SD12 ≥ 34.4 accounting for (56.6%) and 64 patients had Ts - Diff 12 ≥ 105 with 60.4%

the case group

Of the 140 patients studied, we performed Dipyridamole-induced stress myocardial perfusion scans (MPS) for 140 patients (100%) For the group of patients after MI, we performed myocardial perfusion scans

at the time point of 15.8 ± 1.05 days after acute MI

Table 3.10 Comparison of left ventricular dyssynchrony indices on Gated-SPECT in patients after MI and the control group

Indices Patients afte r MI(n =106) Control

The PSD and HBW indices of the patient group after MI are significantly higher than those of the control group

Table 3.11 Parameters evaluating left ventricular dyssynchrony on

Table 3.12 Compatibility of diagnosing LVD between HBW and PSD

3.2 Relationship of left ventricular dyssynchrony on Gate d-SPECT and some clinical characte ristics and e chocardiography in patients afte r MI

3.2.1 Relationship of left ventricular dyssynchrony on Gated-SPECT and some clinical characteristics and echocardiography in patients after MI

Table 3.13 Relationship ofparameters of left ventricular

dyssynchronyon G-SPECT and gender

Paramete rs Male (n = 89)

(X ± SD)

Fe male (n = 17) (X ± SD)

p

(ranksum test) PSD (o) 48.4± 19.12 50.4 ± 21.92 >0.05 HBW (o) 155.5 ± 72.91 151.9 ± 68.85 >0.05

p (test for trend) < 0.05 < 0.05

There are significant differences between the PSD and HBW indices among age groups

Table 3.15 Relationship of parameters of left ventricular dyssynchrony