scholarly journals Left atrial strain in the assessment of diastolic function: providing new insights into primary myocardial dysfunction in Marfan syndrome

2021 ◽  
Author(s):  
Eusebio García-Izquierdo ◽  
Vanessa Moñivas-Palomero ◽  
Alberto Forteza ◽  
Carlos Martín-López ◽  
Mario Torres-Sanabria ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Marfan Syndrome ◽  
Left Atrial ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Volume Index ◽  
Systolic Volume ◽  
End Systolic Volume ◽  
Lv Diastolic Dysfunction

Abstract Previous studies using conventional echocardiographic measurements have reported subclinical left ventricular (LV) diastolic abnormalities in patients with Marfan syndrome (MFS). Left atrial (LA) strain allows an accurate categorization of LV diastolic dysfunction. We aimed to characterize LV myocardial performance in a cohort of MFS patients using STE-derived measurements (LV and LA strain) along with conventional echocardiographic parameters. We studied 127 adult patients with MFS (no prior cardiac surgery or significant valvular regurgitation) and 38 healthy controls. We performed detailed echocardiograms and selected left atrial reservoir strain (LASr) as a surrogate of impaired relaxation. Additionally, we searched for possible determinants of LASr in patients with MFS, with a special focus on the elastic properties of the aorta. In spite of lower E-wave, septal and lateral e’ velocities and average E/e’ ratio in MFS patients, all participants had normal diastolic function according to current guidelines. MFS patients exhibited reduced LV global longitudinal strain (19.3 ± 2.6 vs 21.6 ± 2.1%, p < 0,001) and reduced LASr (32.9 ± 8.5 vs 43.3 ± 7.8%, p < 0.001) compared to controls. In the MFS cohort, we found weak significant (p < 0.05) correlations between LASr and certain parameters: E/A ratio (R = 0.258), E wave (R = 0.226), aortic distensibility (R = 0.222), stiffness index (R=-0.216), LV ejection fraction (R = 0.214), lateral e’ (R = 0.210), LV end-systolic volume index (R=-0.210), LV global longitudinal strain (R = 0.201), septal e’ (R = 0.185). After multivariate analysis, only LV end-systolic volume index and E/A ratio maintained a weak independent association with LASr (R=-0,220; p = 0,017 and R = 0,199; p = 0,046, respectively). In conclusion, LASr is reduced in patients with MFS, which may represent an early stage of LV diastolic dysfunction. LASr is not determined by the elastic properties of the aorta, suggesting that impaired myocardial relaxation is a primary condition in MFS.

Abstract 2819: Identification and Characterization of Super-Responders to Cardiac Resynchronization Therapy: An Echocardiographic Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Amira Zaroui ◽  
Patricia Reant ◽  
Erwan Donal ◽  
Aude Mignot ◽  
Pierre Bordachar ◽  
...  
Keyword(s):  
Cardiac Resynchronization Therapy ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Strain Analysis ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Lv Function ◽  
Resynchronization Therapy ◽  
Systolic Volume ◽  
End Systolic Volume

In some patients, cardiac resynchronization therapy (CRT) has been recently shown to induce a spectacular effect on left ventricular (LV) function and inverted remodeling with nearby normalization of LV contraction. Objectives: To analyze and characterize super-responders (CRTSR) by echocardiography before CRT. 186 patients have been investigated before and 6 months after implantation of a CRT device with conventional indication according to ESC guidelines. Echocardiographies including measurements of LV dimensions, and contraction by 2-dimensional strain, and pressure assessment, mitral valve analysis were performed at baseline and at 6 months in an independent core-center lab. CRTSR were defined as a reduction of end-systolic volume of at least 15% and an ejection fraction (EF)>50% and were compared to normal responder patients (CRTNo, patients with a reduction of end-systolic volume of at least 15% but an EF <50%). 17/186 patients (9.1%) were identified as CRTSR, only 2 with ischemic cardiomyopathy (p<0.01). No difference was observed regarding NYHA status, EKG duration or EF between CRTSR and CRTNo at baseline. CRTSR presented with significant lower end-diastolic and end-systolic diameters (64±9mm vs 73±9mm (p<0.01) and 53±7.4mm vs 63±8.4mm (p<0.01), respectively), and end-diastolic and end-systolic volumes 161±44ml vs 210±76ml (p<0.02) and 123±43ml vs 163±69ml (p<0.01)) as well as a higher LV dP/dt max (714±251mmHg.s −1 vs 527±188 mmHg.s −1 (p<0.05)). Regarding strain analysis, CRTSR had significantly higher longitudinal values than CRTNo (−12.8±3% vs −9±2.6%, p<0.001) whereas no difference was observed for other components (p ns). Global longitudinal strain obtained by ROC curves was identified as the best parameter for predicting CRTSR with a cut-off value of −11% (Se=80%, Spe=87%, AUC=0.89, p<0.002) and was confirmed as an independent predictor by the logistic regression (RR: 21.3, p<0.0001). In a large multicenter study, CRT super-responders (EF>50%) were observed in 9% of the population and were associated with less-depressed LV function as determined by strain analysis. Global longitudinal strain appears to be the best predictor of CRTSR.

scholarly journals P1768 The value of global longitudinal strain in non-alcoholic steatohepatitis-associated cirrhosis

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
Y Dimitroglou ◽  
C Aggeli ◽  
A Alexopoulou ◽  
T Alexopoulos ◽  
A Nitsa ◽  
...  
Keyword(s):  
Left Atrial ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Atrial Volume ◽  
Volume Index ◽  
Atrial Volume ◽  
Left Atrial Volume Index ◽  
Alcoholic Steatohepatitis ◽  
Mitral Annular Velocity ◽  
Cirrhotic Patients

Abstract Introduction Non-alcoholic steatohepatitis (NASH) in patients with metabolic syndrome is a common cause of cirrhosis and has been associated with increased cardiovascular mortality. In patients with liver cirrhosis systolic or diastolic dysfunction can be observed and is independent of the cirrhosis etiology. Only few studies using newer echocardiography indices such as Global Longitudinal Strain (GLS) have been published in cirrhotic patients. Purpose To evaluate GLS in patients with NASH cirrhosis when compared to other etiologies. Methods A total of consecutive 36 cirrhotic patients aged 18-70 were included in our study. Standard speckle-tracking software was used for offline analysis of standard apical views and GLS was calculated. Stroke Volume Index (SVI) was calculated with the Simpson method and a standard 2D, Doppler and Tissue Doppler examination was performed in all patients. Results Median age of the study population was 58 (IQR 50-64) years, 78% were male and 17% had ascites. Cirrhosis was considered decompensated in 21 (58%) of patients. The 28%, 42% and 19% had NASH-associated, alcoholic and viral etiology of cirrhosis, respectively. Median ejection fraction (EF) was 60% (IQR: 57%; 65%) and GLS was -21.1% (-19.7%; -23.1%) in the total population. Absolute value of GLS was lower in patients with NASH cirrhosis compared to other etiologies (p = 0.009) (figure 1). EF, SVI, left atrial volume index (LAVI), E/e’ ratio and mitral annular velocity (e’) did not differ significantly between those with NASH associated cirrhosis and the rest. GLS values were significantly correlated with EF (r=-0.588, p = 0.002), SVI (r=-0.469, p = 0.016) and BNP levels (r=-0.571, p = 0.007), but not with age, left ventricular end diastolic volume, left atrial volume index, E/e’, mitral annular velocity and blood pressure. According to a multivariable linear regression model, NASH etiology [B = 2.1 (0.6; 3.7), p = 0.008)] and EF (per 10% increase) [B=-1.7 (-3.3; -0.2), p = 0.03)] were the only independent factors associated with GLS values in cirrhotic patients. Conclusions GLS values are within normal limits in cirrhotic patients but seem to be affected in patients with NASH associated cirrhosis. Further studies are needed to assess the prognostic implications of this finding. Abstract P1768 Figure 1

481Right ventricular longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A L Chilingaryan ◽  
L G Tunyan ◽  
K G Adamyan
Keyword(s):  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Volume Index ◽  
Asymptomatic Patients ◽  
Lv Ejection Fraction ◽  
Primary Mitral Regurgitation

Abstract Mitral regurgitation (MR) leads to subclinical changes that often cannot be detected by low sensitive conventional parameters and early predictors of deterioration could suggest a better timing for intervention. Methods We follow up 175 asymptomatic patients 56±13 years (79 female) with severe primary MR in sinus rhythm and without diabetes mellitus and renal disease for 2 years. Global longitudinal strain (LS) of left ventricle (LVGLS), right ventricular (RV) free wall LS (RVLS), and left atrial (LA) peak reservoir LS as average of two basal segments in 4 chamber view were measured by speckle tracking along with indexes of LV end-systolic and end-diastolic volumes, LV ejection fraction (EF), left atrial end-systolic volume index (LAVi) every 6 months. Normal reference values of LS were obtained from age and sex matched 40 healthy controls. Results Patients with MR had higher LV ejection fraction (EF), LVGLS, LALS and lower values of RVLS compared with controls (EF 67.4±5% vs 59.3±4%, p<0.05; LVGLS –25.2±2.3% vs –21.2±1.9%, p<0.03; LALS 46.2±5.1% vs 42.4±3.7%, p<0.04; RVLS –23.4±5.1% vs –27.3±2.8%, p<0.03). 53 (30%) patients developed symptoms at exercise during follow up. Symptomatic patients at baseline had higher values of RVLS compared with patients who remained asymptomatic during follow up without significant differences in EF, LVGLS, LALS (RVLS –21.4±2.6% vs –25.8±3.2%, p<0.02; EF 66.8±2.4% vs 68.1±3.1%, p>0.05; LVGLS –24.8±2.1% vs –25.3±2.3%, p>0.05; LALS 45.7±4.1% vs 46.5±4.4%, p>0.05). RVLS correlated with LAVi (r=0.53, p<0.01) and LALS (r=0.57, p<0.01). Regression analysis defined RVLS as an independent predictor of symptoms development (OR=3.2; 95% CI=1.37–7.63; p<0.01). Conclusion RV longitudinal strain predicts symptoms in patients with chronic primary mitral regurgitation.

scholarly journals 1230 The atrial stiffness index in hypertensive women with indeterminate diastolic function

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Y Kolesnyk ◽  
M V Sokolova
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Normal Function ◽  
Stiffness Index ◽  
Additional Parameter ◽  
Deformation Curves ◽  
Additional Information ◽  
Significant Difference

Abstract Background Despite new 2016 ASE/EACVI guidelines on diastolic function (DF), there is still significant amount of patients with indeterminate results. The left atrial (LA) longitudinal strain could provide additional information in case of inconclusive results. Recenty, a new LA stiffness index was proposed as ratio between E/e" and LA global longitudinal strain (GLS). The purpose of this study was to test the diagnostic utility of LA stiffness index in hypertensive women with inderterminate DF. Methods The study enrolled 100 postmenopausal women (mean age 57 ± 4 years) with uncomplicated arterial hypertension, divided into 3 groups (normal DF, indeterminate DF, diastolic dysfunction). The DF was assessed with both 2009 and 2016 ASE/EACVI algorithms. LA longitudinal strain was measured as peak of deformation curves with R-wave variant of ECG triggering. The LA GLS was measured by averaging 12 segmental values. The atrial stiffness index was calculated as E/e" ratio to LA GLS. Results The prevalence of indeterminate DF was higher with assessment by 2016 algorithm (53 % vs 38 %). The E/e" ratio was significantly increased in patients with indeterminate DF compared to normal function (Table). LA GLS was decreased only in patients with inconclusive resuts by 2009 algorithm. LA stiffness index was increased gradually according to diastolic abnormalities severity. The significant difference between three groups was only found with categorization of patients by 2016 algorithm. Conclusions The novel LA stiffness index could be additional parameter of DF assessment in case of indeterminate results. However, it needs further validation in simultaneous echo-invasive studies. LA mechanics in diastolic dysfucntion Parameter Normal diastolic function Indeterminate function Diastolic dysfunction p 2009 guidelines Prevalence, % 31 38 31 E/e" ratio 8,07 (7,36-9,6) 9,91 (8,44-11,6)* 11 (10,52-13)*^ p &lt; 0,0001 LA GLS, % 34,8 (30,2-39,9) 30,8 (26,5-34,9)* 28,9 (24,2-36)* p = 0,028 LA stiffness index 0,24 (0,18-0,31) 0,32 (0,27-0,39)* 0,37 (0,31-0,46)* p &lt; 0,0001 2016 guidelines Prevalence, % 40 53 7 E/e" ratio 8,8 (7,74-10,1) 10 (8,6-11,7)* 14 (12-14,9)*^ p &lt; 0,0001 LA GLS, % 34,2 (28,4-39,1) 30,8 (26,5-34,8) 29,6 (25,1-37,8) p = 0,18 LA stiffness index 0,27 (0,2-0,34) 0,33 (0,27-0,4)* 0,47 (0,38-0,59)*^ p = 0,001 The values are given as median and interquartile range. * - compared to normal function ^ - compared to indeterminate result

scholarly journals Correlations between left ventricular and left atrial function assessed by speckle tracking echocardiography in patients with treated well-controlled arterial hypertension

2020 ◽  
Author(s):  
Beata Uziebło-Życzkowska ◽  
Paweł Krzesiński
Keyword(s):  
Arterial Hypertension ◽  
Diastolic Function ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Speckle Tracking Echocardiography ◽  
Statistical Significance ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Lv Diastolic Function

Abstract BackgroundEven in patients with well-controlled arterial hypertension (AH) and without significant comorbidities left ventricular (LV) and left atrial (LA) strain abnormalities may sometimes be found in speckle-tracking echocardiography. Therefore, the aim of this study was to investigate the correlation between LA strain and LV diastolic and systolic function in a group of patients with treated, well-controlled AH.Methods LA contractile, conduit, and reservoir function, together with echocardiographic signs of LV diastolic function and LV global longitudinal strain (LV GLS), were assessed in 101 patients with treated, well-controlled AH who met the standard criteria of normal LV ejection fraction (LVEF) and normal LV diastolic function.ResultA relevant percentage of study participants presented lower than reference LV and LA strain values. Moreover, there were statistically significant differences in LA longitudinal strain (LAS) values (LAS during reservoir phase—LASr (p<0.001) and LAS during conduit phase—LAScd (p = 0.008)) between patients with high and lower LV GLS, confirmed by significant correlations between LASr, LAScd, and GLS. In the correlations analysis between LAS values and LV diastolic function parameters, statistical significance was obtained for the following: LASct (contraction) vs. e’avg, LASct vs. E/A, LASct vs. A, LAScd vs. e’avg, LAScd vs. E/A, and LAScd vs. A. Conclusions LV and LA strain abnormalities occurred within a significant percentage of patients with treated, well-controlledAH. Impaired LA strain is associated with lower LV strain and reduced LV diastolic function parameters, reflecting both the passive and active properties of the LA.

scholarly journals Left ventricular global longitudinal strain in predicting CRT response: one more J-shaped curve in medicine

2021 ◽  
Author(s):  
Michal Orszulak ◽  
Artur Filipecki ◽  
Wojciech Wrobel ◽  
Adrianna Berger-Kucza ◽  
Witold Orszulak ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Longitudinal Strain ◽  
Speckle Tracking Echocardiography ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Systolic Volume ◽  
End Systolic Volume ◽  
Relationship Of ◽  
Shaped Pattern ◽  
Crt Response

AbstractThe aim of the study was: (1) to verify the hypothesis that left ventricular global longitudinal strain (LVGLS) may be of additive prognostic value in prediction CRT response and (2) to obtain such a LVGLS value that in the best optimal way enables to characterize potential CRT responders. Forty-nine HF patients (age 66.5 ± 10 years, LVEF 24.9 ± 6.4%, LBBB 71.4%, 57.1% ischemic aetiology of HF) underwent CRT implantation. Transthoracic echocardiography was performed prior to and 15 ± 7 months after CRT implantation. Speckle-tracking echocardiography was performed to assess longitudinal left ventricular function as LVGLS. The response to CRT was defined as a ≥ 15% reduction in the left ventricular end-systolic volume (∆LVESV). Thirty-six (73.5%) patients responded to CRT. There was no linear correlation between baseline LVGLS and ∆LVESV (r = 0.09; p = 0.56). The patients were divided according to the percentile of baseline LVGLS: above 80th percentile; between 80 and 40th percentile; below 40th percentile. Two peripheral groups (above 80th and below 40th percentile) formed “peripheral LVGLS” and the middle group was called “mid-range LVGLS”. The absolute LVGLS cutoff values were − 6.07% (40th percentile) and − 8.67% (80th percentile). For the group of 20 (40.8%) “mid-range LVGLS” patients mean ΔLVESV was 33.3 ± 16.9% while for “peripheral LVGLS” ΔLVESV was 16.2 ± 18.8% (p < 0.001). Among non-ischemic HF etiology, all “mid-range LVGLS” patients (100%) responded positively to CRT (in “peripheral LVGLS”—55% responders; p = 0.015). Baseline LVGLS may have a potential prognostic value in prediction CRT response with relationship of inverted J-shaped pattern. “Mid-range LVGLS” values should help to select CRT responders, especially in non-ischemic HF etiology patients.

scholarly journals The loss of left atrial contractile function predicts worse outcome in HFrEF: a speckle tracking study

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
GE Mandoli ◽  
MC Pastore ◽  
G Benfari ◽  
M Setti ◽  
L Maritan ◽  
...  
Keyword(s):  
Sinus Rhythm ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Longitudinal Strain ◽  
Contractile Function ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Volume Index ◽  
Systolic Pulmonary Artery Pressure ◽  
Atrial Contraction

Abstract Funding Acknowledgements Type of funding sources: None. Background in chronic heart failure (HF), high cardiac pressure induces a progressive remodeling of small pulmonary arteries up to pulmonary hypertension development. At the end of left atrial (LA) conduit function, pulmonary and left heart end-systolic pressures equalize. This might affect LA systole. Purpose we investigated whether peak atrial contraction strain (PACS), measured by speckle tracking echocardiography (STE), was independently associated with outcome in HF with reduced ejection fraction(HFrEF). Methods 168 outpatients with HFrEF and sinus-rhythm referred to our echo-labs were prospectively enrolled. After clinical and echocardiographic evaluation, off-line STE analysis was performed. The endpoints were cardiovascular (CV) death and HF hospitalization respectively. Spline knotted survival model identified the optimal cut-off value for PACS. Results The 152 included patients were stratified based on PACS &lt; 8%(n = 76) or PACS≥8%(n = 76). Mean age was 61 ± 12, mean EF was 30 ± 9%. Characteristics of the two groups are presented in Table 1. Over a mean follow-up of 3.41 ± 1.9 years, 117 events (51 CV death, 66 HF hospitalizations) were collected. By univariate and multivariate Cox analysis, global PACS emerged as a strong and independent predictor of CV death and HF hospitalization, even after adjusting for age, sex, LV strain, E/e’, LA volume index (HR 0.6 per 5 unit decrease in PACS). Kaplan Meier curves showed a sustained divergence in event-free survival rates for the two groups (Fig.1). Conclusions The reduction of PACS significantly and independently affects CV outcome in HFrEF. Although limited to patients with sinus rhythm, it could offer additive prognostic information for HFrEF patients. Table 1 Variable PACS &lt; 8 PACS ≥ 8 P value Age 61.5± 11.4 61.8 ± 12.7 0.4 NYHA class &gt;2 26% (n = 39) 11% (n = 17) &lt;0.0001 NT pro BNP 2293.7 ± 1636 1335 ± 242 0.04 E/E’ ratio 16.1 ± 9.09 12.1 ± 7.09 0.0015 LV GLS -7.28 ± 3.4 -10.17 ± 3.2 &lt;0.001 sPAP 40.5 ± 13.7 30.3 ± 9.3 &lt;0.0001 LAVI 64.4 ± 20.4 45.5 ± 15.8 &lt;0.0001 PALS 9.8 ± 4.9 20.2 ± 7 &lt;0.0001 E, peak early diastolic “E” wave; E’, medium velocity of early mitral annulus descent; GLS, global longitudinal strain; LAVI, left atrial volume index; LV, left ventricular; PACS, peak atrial contraction strain; PALS, peak atrial longitudinal strain; sPAP, systolic pulmonary artery pressure. Abstract Figure. Fig.1

P1482Preclinical diastolic dysfunction assessed by left atrial strain and association with incident heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Potter ◽  
S Ramkumar ◽  
H Yang ◽  
H Kawakami ◽  
K Negishi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Left Atrial ◽  
Left Ventricular ◽  
Community Dwelling ◽  
Volume Index ◽  
P Value ◽  
Left Atrial Strain ◽  
Atrial Strain

Abstract Background Left atrial strain in the reservoir phase (LASr) measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). However, reduced LASr has not been prospectively validated against clinical heart failure (HF) endpoints and its place in diastology evaluation is unclear. Aim We sought whether DD grades defined by previously validated ranges of LASr predicted incident HF and whether reclassifying indeterminate diastolic function based on reduced LASr could facilitate assessment of HF risk. Methods Community dwelling elderly subjects were recruited and underwent baseline clinical and echocardiographic assessment. Where imaging was suitable, speckle-tracking echocardiography assessed LASr and subjects were assigned DD grades based on published ranges: normal >35%, grade 1 24–35%, grade 2 19–24%, grade 3 <19%. Current ASE/EACVI recommendations were used to identify those with indeterminate function; LASr-defined DD (LASr-DD) was defined as LASr ≤23%. Follow-up was ≤2 years and incident HF adjudicated by Framingham criteria. Results Of 610 subjects (age 71±5 yrs., 46% male) LASr analysis was feasible in 590 (97%); average LASr was 39% (IQR 34–43%). Incident HF was associated with LASr-DD grade, occurring in 8 (36%) with grade ≥2, 14 (10%) with grade 1 and 39 (9%) with normal function (p<0.001). Adjusted odds ratio for incident HF for LASr-DD grade ≥2 was 3.12 (95% CI 1.06–9.1, p=0.038) Diastolic function was indeterminate in 147 (24%) subjects; of 144 (98%) with LAS analysis, 6 (75%) of those with LASr-DD vs. 15 (11%) with normal LASr experienced incident HF (p<0.001). Univariable Multivariable* OR (95% CI) p-value OR (95% CI) p-value LASr-DD grade:   1 1.13 (0.59–2.15) 0.7 0.84 (0.42–1.69) 0.63   ≥2 5.7 (2.26–14.5) <0.001 3.12 (1.06–9.1) 0.038 *Adjusted for age, hypertension, diabetes, BMI, global longitudinal strain, E/e', LA volume index, LV mass index (all p<0.1 on univariable analysis). Incorporating LA strain in practice Conclusion DD defined by LASr is predictive of HF for grades ≥2 independent of other diastolic measures. Indeterminate diastolic function with LASr ≤23% is associated with incident HF. LASr may complement current diastolic function assessment recommendations. Acknowledgement/Funding Baker Heart and Diabetes Institute

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