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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: Ass Prof PhD Le Thi Viet Hoa Ass Prof PhD Phạm Nguyen Son Reviewer: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute Pharmaceutical Sciences of Clinical Medical and THE PUBLISHED ARTICLES RELATED TO THIS STUDY 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), pp.34-38 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 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 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 The structure of thesis The thesis includes 119 pages, with introduction and aims of study 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 pages There are 27 tables of data, 15 charts, 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 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 - Assessment of RV function - LA function 1.4.3 Some studies regarding speckle tracking echocardiography in septic shock The first study evaluating this in 2014 by Landesberg et al demonstrate the association between diastolic strain measured by longitudinal strain early diastolic filling wave and in-hospital mortality (Wald test = 6.6; p =0.02) A subsequent study by Orde et al (2014) on 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 0,05 LVOT (mm) 20,56 ± 1,25 20,05 ± 1,73 p > 0,05 VTI (cm) 19,26 ± 3,95 19,05 ± 4,02 p > 0,05 FS (%) 32,8 ± 5,8 34,7 ± 5,9 p > 0,05 LVEF (%) 60,5 ± 8,5 63,5 ± 8,2 p > 0,05 Parameters (Simpson) There were no significant differences in left ventricular ejection fraction in two groups Table 3.12 Left ventricular longitudinal strain at timing of T0 in the study group Group Sepsis Septic shock (n = 37) (n = 90) p LS-4C (%) -17,0 ± 2,7 -14,5± 3,3 p < 0,01 LS-2C (%) -16,9 ± 2,8 -14,3± 3,9 p < 0,01 LS-3C (%) -17,1 ± 2,6 -15,1± 3,7 p < 0,01 GLS (%) -17,1 ± 3,3 -14,6 ± 3,3 p < 0,01 Parameters Left ventricular systolic function via left ventricular longitudinal strain in septic shock group was lower than that in sepsis group 14 12.2% 87.8% Left ventricular systolic dysfunction Non-Left ventricular systolic dysfunction Chart 3.1 Percentage of left ventricular systolic dysfunction by conventional echocardiography in septic shock patients Percentage of left ventricular systolic dysfunction in septic shockpatients by conventional echocardiograpy (12.2%) echocardiography (12.2%) 44.4% 55.6% Left ventricular systolic dysfunction Non-Left ventricular systolic dysfunction Chart 3.2 Percentage of left ventricular systolic dysfunction by speckle tracing echocardiography in septic shock patients Percentage of left ventricular systolic dysfunction in septic shock patients by speckle trcking echocardiograpy (55.6%) 15 Table 3.15 The relationship between left ventricular longitudinal strain and left ventricular ejection fraction at the timing of T0 in septic shock group < 50% ≥ 50% (n = 11) (n = 79) p LS-4C (%) -11,9 ± 3,8 -14,6 ± 3,2 p < 0,01 LS-2C (%) -10,4 ± 4,1 -14,6 ± 3,7 p < 0,01 LS-3C (%) -9,6 ± 3,6 -15,5 ± 3,4 p < 0,01 GLS (%) -10,6 ± 3,7 -14,9 ± 3,1 p < 0,01 LVEF Parameters Left ventricular systolic function via left ventricular longitudinal strain in LVEF < 50% was lower than that in LVEF ≥ 50% 49.4% 50.6% Left ventricular systolic dysfunction Non-Left ventricular systolic dysfunction Chart 3.2 Percentage of left ventricular systolic dysfunction by speckle tracking echocardiography in septic shock patients with preserved left ventricular ejection fraction Percentage of left ventricular systolic dysfunction by speckle tracing echocardiography in septic shock patients with preserved left ventricular ejection fraction (50.6%) 16 3.2.2 Changes in left ventricular longitudinal strain by speckle tracking echocardiography in patients with septic shock Table 3.14 Left ventricular longitudinal strain at times in septic shock Times T0 T1 Parameters (n = 90) (n = 57 ) p LS-4C (%) -14,5± 3,3 -17,2 ± 3,1 p < 0,01 LS-2C (%) -14,3± 3,9 -17,2 ± 2,4 p < 0,01 LS-3C (%) -15,1± 3,7 -18,5 ± 4,3 p < 0,01 GLS (%) -14,6 ± 3,3 -17,8 ± 2,4 p < 0,01 Left ventricular systolic function via left ventricular longitudinal strain at the timing of septic shock recovery improved compared to at the timing of septic shock onset Table 3.20 Left ventricular longitudinal strain at timing of T0 between nonsurvivor and survivor group in septic shock patients Outcome Nonsurvivor Survivor Parameters (n = 39) (n = 51) p LS-4C (%) -12,8 ± 3,1 -15,7 ± 2,9 p < 0,01 LS-2C (%) -12,7 ± 3,9 -15,5 ± 3,4 p < 0,01 LS-3C (%) -13,6 ± 3,7 -16,3 ± 3,3 p < 0,01 GLS (%) -13,1 ± 3,2 -15,8 ± 2,9 p < 0,01 Left ventricular systolic function via left ventricular longitudinal strain in survivor group was significantly better than nonsurvivor group 3.3 The association of global longitudinal strain with some prognostic factors in patients with septic shock 3.3.1 The association of GLS with some prognostic factors at timing of T0 in patients with septic shock - GLS has a positive correlation, the moderate level with the SOFA score (r = 0.3; p < 0.01), the APACHE II score (r = 0.48; p 0.05 The serum NT-proBNP, hs-Troponin T and Lactat level at T0 had not predictive mortality value in patients with septic shock 18 Table 3.25 Compare the predictive mortality value of GLS with other parameters in septic shock patients Parameters GLS (AUC = 0.77) APACHE II (AUC = 0.78) p > 0.05 SOFA (AUC = 0.73) p > 0.05 SAPS (AUC = 0.72) p > 0.05 NT-proBNP (AUC = 0.58) p < 0.05 hs-Troponin T (AUC = ,52) p < 0.05 Lactat (AUC = 0.57) p < 0.05 GLS + APACHE II (AUC = 0.8) p > 0.05 GLS + SOFA (AUC = 0.79) p > 0.05 GLS + SAPS (AUC = 0.79) p > 0.05 GLS + NT-proBNP (AUC = 0.77) p > 0.05 GLS + hs-Troponin T (AUC = 0.79) p > 0.05 GLS + Lactat (AUC = 0.77) p > 0.05 The GLS has predictive mortality value similar to APACHE II, SOFA, SAPS score (p > 0.05) and better than serum NT-proBNP, hsTroponin T and Lactat at T0 (p < 0.05) Bảng 3.27 Multiple logistic regression analysis of risk factors for mortality in septic shock Factors OR CI 95% p 2.9 0.8 – 10.9 p > 0.05 Age (year) 1.8 0.5 – 6.3 p > 0.05 Lactate > mmol/l 2.4 0.6 – 10.0 p > 0.05 Vasoactive-inotrope score > 22,5 4.4 1.3– 15.1 GLS > -14,2% p < 0.05 6.1 1.5– 24.8 APACHE II > 19 points p < 0.05 2.0 0.5 – 7.5 p > 0.05 NT-ProBNP > 14037 pg/ml GLS > -14.2% and APACHE II > 19 points were independent prognostic factors in predicting mortality in septic shock patients 19 Chapter DISCUSSION 4.1 Common characteristics of patients 4.1.1 Clinical and subclinical characteristics in the research group - The average age in septic shock group was 68.8 ± 15.1 years; the lowest age was 23 years old and the highest age was 98 years old The average age in the nonsurvivor group was 68.4 ± 17.4 (age) not different from the survivor group 69.1 ± 13.1 (age) Men accounted for the majority, in the group of septic shock was 74.4%, in the septic group was 89.2% There is no gender difference between the two groups The results of our study are similar to some authors such as Bui Thi Huong Giang (2015), Orde et al (2014), Palmier (2015) - Site of infection from respiratory and digestive tract accounted for 47.8% and 38.9%, respectively Compared with other studies: Bui Thi Huong Giang (2016), respiratory tract (37.2%), digestive tract (29.5%) - The positive blood culture rate in the septic shock was 35.6% Gram negative bacteria accounted for 65.6% in which the highest percentage of Escherichia Coli (43.7%) Compared with other studies: Pham Thi Ngoc Thao (2013), positive blood culture rate (33.9%), gram negative bacteria (83.8%) of which Acinetobacter was the most common cause (27%) - Lactate and procalcitonin level at the timing of septic shock onset was significantly higher than the time of septic shock recovery and sepsis group The NT-proBNP level in the nonsurvivor group was higher than in the survivor group (p