Abstract of medical PHD thesis: Research on the changes and predictive value of left ventricular longitudinal strain by speckle tracking echocardiography in septic shock patients

The new conclusions of this study: Speckle tracking echocardiography can detect significant left ventricular impairment in patients with septic shock, which was not otherwise detectable by conventional echocardiography.

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

PHAM DANG HAI

RESEARCH ON THE CHANGES AND PREDICTIVE VALUE OF LEFT VENTRICULAR LONGITUDINAL STRAIN

BY SPECKLE TRACKING ECHOCARDIOGRAPHY IN

SEPTIC SHOCK PATIENTS

Speciality: Anesthesiology and critical care

Code: 62720122

ABSTRACT OF MEDICAL PHD THESIS

Hà Nội – Năm 2019

THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

Supervisor:

1 Ass Prof PhD Le Thi Viet Hoa

2 Ass Prof PhD Phạm Nguyen Son

Day Month Year

The thesis can be found at:

1 National Library of Vietnam

2 Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences

THE PUBLISHED ARTICLES RELATED TO THIS STUDY

1 Pham Dang Hai, Do Van Quyen, Le Thi Viet Hoa, Pham Nguyen

Son (2019) “Left ventricular systolic function in septic shock by speckle-tracking echocardiography”, Journal of 108 clinical medicine and pharmacy, vol 1 (1), pp.34-38

2 Pham Dang Hai, Do Van Quyen, Le Thi Viet Hoa, Pham Nguyen

Son (2019) “Prognostic value of global longitudinal strain in patients with septic shock” Journal of 108 clinical medicine and pharmacy, vol (1), pp.46-50

INTRODUCTON

1 The urgent and demand of the study

Septic shock is the major cause of hospitalization and also the leading cause of death in ICU Septic shock can lead to organs dysfunction including cardiovascular system Prevalence of cardiac dysfunction in patients with septic shock is aproximately 60-70% This disorder aggravates the condidtion of disease and increases the mortality rate Echocardiography is nowadays one of the first line investigations in patients with septic shock because of its accessibility and noninvasive nature In sepsis and septic shock, however, assessment of myocardial function by conventional echocardiographic parameters such as left ventricular ejection fraction (LVEF) is affected to a large degree by ongoing changes in preload and afterload conditions

Speckle tracking echocardiography (STE) is a novel technology

of echocardiography Compared to LVEF, STE is affected to a much lesser degree by changes in ventricular loading conditions, angle -independent and reproducible This method based on a semi-automated algorithm that tracks the displacement of acoustic “speckles” in the myocardium, the change in length of myocardial segments are measured Global longitudinal strain is a valuable index in assessing left ventricular function, in the prognosis of cardiovascular events and mortality prognosis In worldwide, the application of STE in clinical practice is being studied, especially in investigating cardiac function in patients with septic shock However, there have not been any studies about it in Vietnam Therefore, this is a novel and scientific issue and maybe benefits

to doctors in the management of septic shock

2 The new conclusions of this study

- Speckle tracking echocardiography can detect significant left ventricular impairment in patients with septic shock, which was not otherwise detectable by conventional echocardiography

- GLS is valuable in prognosis of severity in patients with septic shock through correlation with severity score (APACHE II, SOFA, SAPS2), biomarker (NT-proBNP, hs-Troponin T, Lactat) and number of organ dysfuctions

- GLS has predictive mortality value in septic shock patients

3 The aims of this study

- To evaluate some characteristics of changes in left ventricular longitudinal strain by Speckle tracking echocardiography in patients with septic shock

- To determine the association of global longitudinal strain with some prognostic factors in patients with septic shock

4 The structure of thesis

The thesis includes 119 pages, with introduction and aims of study 2 pages Chapter one: overview 34 pages, chapter two: subject and method

25 pages; chapter three: results 24 pages; chapter four: discussion 27 pages, conclusion and recommendation 3 pages There are 27 tables of data, 15 charts, 9 pictures and figures The reference section has 169 articles including 157 English and 12 Vietnamese articles Two study–related articles were published

Chapter one OVERVIEW 1.1 Septic shock

1.1.1 Definition of septic shock

In 2016, A task force with expertise of society of Critical Care Medicine and the European Society of Intensive Care Medicine gave new definition of sepsis and septic shock

- Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection

- Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough

to substantially increase mortality Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate level greater than 2 mmol/L in the absence of hypovolemia

1.1.2 Risk factors of sepsis and septic shock

Some risk factors of sepsis and septic shock include:

- Intensive care unit admission

- Advanced age (≥ 65 years)

- Immunosuppression

- Diabetes and cancer

- Previous hospitalization

1.1.3 Prognosis of sepsis and septic shock

Prognostic factors include clinical characteristics that impact the severity of sepsis, the host's response to infection, the site and type of infection, and the timing and type of antimicrobial therapy

1.2 Cardiac dysfunction in septic shock

1.2.1 The clinical characteristics of sepsis induced myocardial dysfunction

- Increased cardiac output and decreased systemic vascular resistence

- Patients who survived had a depressed left ventricular EF and acute left ventricular dilatation However, nonsurvivors of septic shock maintained normal left ventricular EF and volume

1.2.2 Pathogenesis of sepsis induced myocardial dysfunction

- Role of coronary blood flow

- Myocardium-depressing factors

- Autonomic dysregulation

- Dysfunction of intracellular Ca2+ transporters in cardiomyocytes

- Energetic starvation of cardiomyocytes

- Mitochondrial dysfunction and oxidative-nitrosative stress

1.3 Image methods evaluating cardiac function in septic shock

- Transthoracic echocardiography

- Cardiac magnetic resonance imaging

- Myocardial perfusion imaging (MPI)

1.4 Speckle tracking echocardiography

1.4.1 Parameters of speckle tracking echocardiography

- Strain

- Strain rate

1.4.2 Clinical applications

- Detection of subclinical myocardial dysfunction

- Monitoring response to treatment

- Role in acute coronary event

- As a measure of myocardial ischemia and viability

- Role in cardiac resynchronization therapy

- Assessment of LV diastolic function

60 adult patients with severe sepsis or septic shock, 33% of patients had left ventricle (LV) dysfunction based on ejection fraction compared to 69% assessed with STE

Lui et al (2015), the non-survivors exhibited GLSs that were less negative than those of the survivors (non-survivors vs survivors: -11.8 ± 4.5% vs -15.0±3.6%, p <0.001), which indicated worse LV systolic function The patients with GLS ≥-13% exhibited higher ICU and in-hospital mortality rates (hazard ratio: 4.34, p <0.001 and hazard ratio: 4.21, p <0.001, respectively) Cox regression analyses revealed that higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores and less negative GLS were independent predictors of ICU and in-hospital mortalities

In SPECKSS study (2016), Septic shock group had a greater degree

of myocardial dysfunction measured by global longitudinal strain (GLS) than sepsis group (-14.5 % vs -18.3 %, p < 0.001), and the myocardial strain differed upon diagnosis and recovery (-14.5 % vs -16.0 %, P = 0.010) Conventional echocardiographic measurements such as LVEF (59 % in the study group vs 61 % in the control group, p = 0.169) did not differ between the two groups

Innocenti et al (2018), Analyses through ROC curves focusing on day-7 mortality show that less negative GLS (AUC 0.73, p = 0.001) In multivariate analyses, mortality by day-7 follow-up is more likely per higher GLS (i.e., indicative of worst systolic dysfunction, HR 1.22/%,

p = 0.005) and the same analysis by 28-day follow-up, LV GLS is an independent prognostic value ((RR 1,14; KTC 95%: 1,03–1,26, p = 0,009)

Some issues need further research

- To determine the prognostic value of the severity through the

correlation between GLS with scores such as SOFA, APACHE II and

SAPS 2 as well as biomarkers (hs-Troponin T, NT-proBNP, Lactat)

- To determine cut- off value of GLS in predictor of mortality

Chapter two SUBJECTS AND METHOD 2.1 Subjects

From May 2017 to December 2018, we prospectively studied

127 patients admitted to the ICU of 108 Military Central Hospital, divided 2 groups: 90 patients with septic shock and 37 patients with sepsis

2.1.1 Study group

Include criteria

- Age 18 years or older,

- Diagnosis of septic shock according to SCCM/ESICM (2016)

Exclude criteria

Patients were excluded if they met one of the following criteria:

- Active diagnoses directly relating to myocardial dysfunction, such as acute myocardial infarction, myocarditis and post-cardiopulmonary resuscitation status;

- Significant underlying cardiac conditions, such as congenital heart disease, valvular heart disease, and cardiomyopathy

2.1.2 Control group

Inclusion criteria

- Age 18 years or older,

- Diagnosis of sepsis according to SCCM/ESICM (2016)

Exclusion criteria

Patients were excluded if they met one of the following criteria:

- Active diagnoses directly relating to myocardial dysfunction, such as acute myocardial infarction, myocarditis and post-cardiopulmonary resuscitation status;

- Significant underlying cardiac conditions, such as congenital heart disease, valvular heart disease, and cardiomyopathy

2.1.3 Withdrawal criteria in study

- Patients who are eligible for study but the patient's family demands

to stop the management

- Poor quality echocardiography images do not qualify for analysis

- Hemodynamic and respiratory monitoring devices

- Machines for continuous renal replacement therapy

- Hematological and biochemical tests are performed on parameter testing machines at 108 Military Central Hospital

multi Vivid S5 Cardiovascular Ultrasound Machine

2.2.4 Research contents and evaluation criteria

2.2.4.1 Some general characteristics in patients with septic shock

- Clinical and subclinical characteristics in patients with septic shock + Determining characteristics of age, gender, number of organ dysfunction, score of severity

+ Describe some biochemical test results

- Identify several mortality-related clinical and subclinical factors in patients with septic shock

- Results (the mean length of stay in the ICU, percentage of mechanical ventilation, length of stay on mechanical ventilation, percentage of CRRT and mortality)

2.2.4.2 Some characteristics of changes in left ventricular longitudinal strain by speckle tracking echocardiography in patients with septic shock

Content 1: left ventricular longitudinal strain by speckle tracking

echocardiography in evaluating left ventricular systolic function versus left ventricular ejection fraction by conventional echocardiography

Content 2: Some characteristics of changes in left ventricular

longitudinal strain by speckle tracking echocardiography in patients with septic shock

° Evaluation criteria:

- Left ventricular longitudinal strain at the study times: Timing of septic shock onset(T0) and timing of septic shock recovery (T1)

- Left ventricular longitudinal strain at the time of T0 by age group

- Left ventricular longitudinal strain at time of T0 by gender

- Left ventricular longitudinal strain at time of T0 according to the number of organs dysfunction

- Left ventricular longitudinal strain at time T0 according to microbiological causes (gram negative bacteria, gram-positive bacteria and fungi)

- Left ventricular longitudinal strain at the time of T0 in the survivor and nonsurvivor group at the hospital

2.2.4.3 The association of global longitudinal strain with some

prognostic factors in patients with septic shock

Content 1: The association of GLS with some prognostic factors in

patients with septic shock.

- Determination of correlation between GLS and the number of organs dysfunction

Content 2: the value of left ventricular global longitudinal strain in the prognosis of mortality in patients with septic shock

° Evaluation criteria:

- Analyzing the ROC curve in the mortality prognosis of GLS compared

to APACHE II score, SOFA score and SAPS 2 score

- Analyzing the ROC curve in the mortality prognosis of GLS

compared to serum NT-proBNP, hs-troponin T and lactat

- Analysis of ROC curve of GLS in mortality prognosis when combined with APACHE II, SOFA and SAPS2 score compared to GLS alone

- Analysis of ROC curve of GLS in mortality prognosis when combined with NT-proBNP, hs-Troponin T and Lactat compared with GLS alone

- Univariate and multivariate regression analysis of GLS and other

parameters to predict the mortality

2.2.5 Conducting research and data collection

2.2.5.1 Time to conduct research

- T0: Timing of septic shock onset

- T1: Timing of septic shock recovery

2.2.5.2 Enrollment of patients

2.2.5.3 Collection of the initial parameters

2.2.5.4 Management of the septic shock patients according SCC 2016 2.2.5.5 The main techniques protocol in the study

(1) Two-dimensional transthoracic echocardiography: measure the

left ventricular ejection fraction (Simpson)

(2) Two-dimensional speckle tracking echocardiography

- Collect images from the apical four-chamber, apical two-chamber and three-chamber views, takes each image with 3 consecutive cardiac cycles Then copy these images to the CD

- Image analysis using EchoPAC software (version 112, GE - USA) following the steps below:

+ Select images in each recorded apical four-chamber, two-chamber and three-chamber views

+ Choose 3 points (two points on either side of the valve, 1 point at the heart's apex)

+ The software will automatically trace along the border of the left ventricular endothelium according to each views to be analyzed If the automated frame selection seems inaccurate, the same can be adjusted manually.Then the software will automatically analyze to find the strain

of each view and global longitudinal strain

- Left ventricular systolic function parameters:

+ Apical four-chamber longitudinal strain

+ Apical three-chamber longitudinal strain

+ Apical two-chamber longitudinal strain

2.2.6 Criteria using in the study

- Sepsis and septic shock according to SCCM/ESICM (2016)

- Organ dysfunction according to Knaus (1989)

- Left ventricular systolic dysfunction by conventional

echocardiography according to ESC (2016)

- Left ventricular systolic dysfunction by STE according to Dalla (2012)

2.2.7 Statistics and data analysis

All data were assessed by SPSS Software, version 20.0 and Medcalc

14.8.1.0