scholarly journals Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Bandera ◽  
R Martone ◽  
L Chacko ◽  
S Ganesananthan ◽  
JA Gilbertson ◽  
...  
Keyword(s):  
Left Atrial ◽  
Speckle Tracking ◽  
Contractile Function ◽  
Clinical Importance ◽  
Transthyretin Amyloidosis ◽  
Funding Sources ◽  
Atrial Contraction ◽  
Congo Red Staining ◽  
Distinctive Phenotype ◽  
Normal Architecture

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION  The clinical significance of left atrial (LA) involvement in ATTR amyloidosis cardiomyopathy (ATTR-CM) has not been characterized. The aims of this study were to characterize: (1)LA pathology in explanted ATTR-CM hearts; (2)LA mechanics using echocardiographic speckle-tracking in a large cohort of ATTR-CM patients; (3)to study the association with mortality. METHODS AND RESULTS Congo red staining and immunohistochemistry was performed to assess the presence, type and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle-tracking was used to assess LA reservoir, conduit, contractile function and stiffness in 906 ATTR-CM patients (551 wt-ATTR-CM;93 T60A-ATTR-CM;241 V122I-ATTR-CM;21 other). There was extensive ATTR amyloid infiltration in the 5 atria with loss of normal architecture, vessels remodelling, capillary disruption and subendocardial fibrosis. Echo speckle-tracking in 906 ATTR-CM patients demonstrated increased atrial stiffness [median(25th-75th quartile) 1.83(1.15-2.92)] that remained independently associated with prognosis, after adjusting for known predictors (lnLA stiff:HR = 1.26,CI 1.07-1.57;p = 0.009). There was substantial impairment of the three phasic functional atrial components [reservoir 8.86(5.94-12.97)%; conduit 6.5(4.53-9.28)%; contraction function 4.0(2.29-6.56)%]. Atrial contraction was absent in 21.6% of patients whose ECG showed sinus rhythm (SR)-"atrial electro-mechanical dissociation"(AEMD). AEMD was associated with poorer prognosis compared to SR patients with effective mechanical contraction (p < 0.0001). AEMD conferred a similar prognosis to patients in AF. CONCLUSION The phenotype of ATTR-CM includes significant infiltration of the atrial walls with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis. Abstract Figure.

Abstract 13148: Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Francesco Bandera ◽  
Raffaele Martone ◽  
Liza Chacko ◽  
Sharmananthan Ganesananthan ◽  
Thirusha Lane ◽  
...  
Keyword(s):  
Left Atrial ◽  
Contractile Function ◽  
Clinical Importance ◽  
Loss Of Function ◽  
Transthyretin Amyloidosis ◽  
Congo Red Staining ◽  
Clinically Significant ◽  
Normal Architecture ◽  
Strong Independent Predictor ◽  
Functional Phenotype

Introduction: The clinical significance of left atrial (LA) involvement and dysfunction in ATTR amyloidosis cardiomyopathy (ATTR-CM) has not been characterized. We sought to study: 1) LA pathology in heart specimens from ATTR-CM patients 2) LA stiffness and mechanics using echocardiographic speckle tracking (EST) in cardiac ATTR-CM 3) the association between parameters of atrial function and mortality. Methods: Congo red staining and immunohistochemistry was performed to assess amyloid in the atria from 5 ATTR-CM heart specimens. 2D EST was used to assess LA reservoir, conduit, contractile function and stiffness in 906 ATTR-CM patients (551 wt ATTR; 93 T60A ATTR; 241 V122I ATTR; and 21 other gene variants). Results: There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, infiltration and remodelling of vessels, capillary disruption and subendocardial fibrosis. EST demonstrated increased atrial stiffness [median (25th-75th quartile) 1.83 (1.15-2.92)] that remained independently associated with reduced survival, after adjusting for known prognostic variables (lnLA stiff: HR= 1.26, CI 1.07-1.57; p=.009). There was substantial impairment of the three phasic functional atrial components [reservoir 8.86(5.94-12.97)%; conduit 6.5(4.53-9.28)%; and contraction 4.0(2.29-6.56)%]. Atrial contractile function was absent in 21.6% of patients whose ECG showed sinus rhythm (SR)-atrial electro-mechanical dissociation (AEMD). AEMD was associated with a poorer prognosis compared to SR patients who had effective mechanical contraction (p <.0001). AEMD conferred a similar prognosis to patients in AF. Conclusions: The phenotype of ATTR-CM includes clinically significant infiltration of the atrial walls characterized by progressive loss of function and increased stiffness, a strong independent predictor of mortality. AEMD emerged as a distinctive functional phenotype identifying patients in SR with poor prognosis.

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

scholarly journals Clinical Importance of Left Atrial Infiltration in Cardiac Transthyretin Amyloidosis

2021 ◽  
Author(s):  
Francesco Bandera ◽  
Raffaele Martone ◽  
Liza Chacko ◽  
Sharmananthan Ganesananthan ◽  
Janet A. Gilbertson ◽  
...  
Keyword(s):  
Left Atrial ◽  
Clinical Importance ◽  
Transthyretin Amyloidosis

Atrial contraction and mitral annular dynamics during acute left atrial and ventricular ischemia in sheep

2002 ◽  
Vol 283 (5) ◽  
pp. H1929-H1935 ◽  
Author(s):  
Tomasz A. Timek ◽  
David T. Lai ◽  
Frederick Tibayan ◽  
George T. Daughters ◽  
David Liang ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Mitral Regurgitation ◽  
Left Atrial ◽  
Contractile Function ◽  
Mitral Annulus ◽  
Balloon Occlusion ◽  
Valve Closure ◽  
Area Reduction ◽  
Atrial Contraction ◽  
Radiopaque Markers

In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial contractile function, as observed during acute posterolateral ischemia, is linked to diminished presystolic mitral annular reduction, a larger mitral annular size at end diastole, and MR.

scholarly journals Left atrial reservoir strain is reduced in patients with myocardial infarction with non-obstructive coronary arteries

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Malaty ◽  
H H L Chen ◽  
G Gan
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Global Longitudinal Strain ◽  
Strain Analysis ◽  
Left Ventricular ◽  
Funding Sources ◽  
Group Position ◽  
Lv Dysfunction

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a management conundrum given the poorly understood pathogenic mechanisms. In recent years, novel echocardiographic measures such as deformation/strain analysis have enabled early identification of left atrial (LA) remodelling and dysfunction which take place prior to structural alterations. LA dysfunction is an important biomarker of cardiovascular disease and an independent predictor of atrial arrhythmias which may play a fundamental role in the pathogenesis of MINOCA. Purpose The goal of our study was to evaluate and characterise LA function by speckle tracking strain echocardiography in patients with MINOCA. Methods Patients admitted to our institution with acute myocardial infarction were assessed and those diagnosed with MINOCA who underwent transthoracic echocardiogram (TTE) within 48-hours of their coronary angiogram were included. Diagnosis of MINOCA was based on the 2017 ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Two-dimensional speckle tracking strain analysis of the LA and left ventricle (LV) was performed offline using vendor independent software (TomTec Arena). Clinical and echocardiographic measures were compared to healthy controls identified from our echocardiography database. We excluded patients with history of atrial fibrillation, heart failure and LV dysfunction (LVEF &lt;50%). Results The cohort consisted of 82 patients; 41 patients with MINOCA were compared to 41 age and sex matched controls (61% male, mean age 51±12.8 years). At baseline, patients with MINOCA had a higher prevalence of modifiable vascular risk factors including smoking, hypertension and diabetes (p&lt;0.001 for all). Of the echocardiographic parameters, no differences in left ventricular (LV) parameters including LV global longitudinal strain (p=0.463), indexed LV mass (p=0.084) and the E/e' (p=0.391) was appreciated. Though there was no difference in LA volumes or volumetric parameters of LA function (LAEF; p=0.328), patients with MINOCA had a lower LA reservoir strain (29.7±8.5% vs 33.2±6.5%; p=0.04; 95% CI 0.32–5.33). Conclusion Patients with MINOCA demonstrated lower LASr despite normal LV and LA volumes. This suggests that LA dysfunction may play a role in the pathogenesis of MINOCA. Further studies are required to evaluate the significance of our findings. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Use of speckle-tracking echocardiography to stratify risk of atrial fibrillation-related stroke: comparison of left atrial and atrial appendage mechanics

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
Y Mao ◽  
Y Yang ◽  
C Yu ◽  
MM Ma ◽  
YH Wang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Univariate Analysis ◽  
Diagnostic Value ◽  
P Value ◽  
Analysis Model ◽  
Time To Peak ◽  
Funding Sources ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Natural Science Foundation of China onbehalf Sir Run Run Shaw Hospital,Zhejiang University,School of Medicine Background Left atrial (LA) and appendage (LAA) dysfunction were associated with increased risk of stroke in atrial fibrillation. However, usefulness of LA and LAA mechanics has not been fully compared. Methods:201 AF patients were prospectively enrolled. 42(20.8%) had previous stroke/TIA.  Speckle tracking was used to measure LA and LAA peak postive strain. LA and LAA MD was defined as the SD of time to peak positive strain corrected by the R-R interval. Results:LA MD and LAA MD were independently associated with stroke/TIA. The model based on CHA2DS2-VASc score for discrimination of stroke was significantly improved by adding LA MD or LAA MD (P &lt; 0.01). Diagnostic value of LA MD was better than LAA MD in patients with normal LA volumes, while LAA MD was more useful in patients with LA enlargement.Conclusion:Both LA and LAA mechanics had incremental value over CHA2DS2VASc score. However, priorities of strain assessment depend on patients’ LA volume. Variables Univariate analysis Multivariate analysis Model 1 Model 2 Model 3 OR (95% CI) P value OR (95% CI) P value OR (95% CI) p value OR (95% CI) P value Clinical parameters Age 1.09(1.04-1.14) &lt;0.001 1.11(1.04-1.17) 0.001 1.11(1.05-1.17) 0.001 1.11(1.04-1.17) 0.001 BMI 0.988(0.89-1.10) 0.84 1.07(0.92-1.25) 0.40 1.07(0.91-1.25) 0.40 CHA2DS2-VASc score 1.52(1.15-2.00) 0.003 1.08(0.67-1.74) 0.76 1.08(0.65-1.80) 0.77 1.10(0.69-1.76) 0.69 Persistent AF 1.88(0.94-3.74) 0.07 0.75(0.23-2.40) 0.63 0.87(0.27-2.81) 0.82 Therapeutic anticoagulation 0.56(0.28-1.11) 0.10 0.22(0.09-0.57) 0.002 0.23(0.09-0.59) 0.002 0.22(0.09-0.57) 0.002 LA parameters LAEF 0.96(0.94-0.99) 0.002 0.982(0.953-1.01) 0.26 iLAVmin 1.03(1.01-1.05) 0.006 0.98(0.94-1.02) 0.27 LA MD 1.22(1.10-1.36) &lt;0.001 1.16(1.02-1.32) 0.02 1.18(1.03-1.34) 0.02 1.16(1.02-1.32) 0.02 LA GLS 0.935(0.893-0.98) 0.005 1.0(0.953-1.14) 0.36 1.02(0.94-1.12) 0.59 1.02(0.94-1.10) 0.72 LAA parameters LAAEV 0.12(0.02-0.74) 0.02 3.34(0.31-36.06) 0.32 LAA EF 0.98(0.96-1.00) 0.06 1.01(0.98-1.04) 0.65 LAA GLS 0.85(0.77-0.94) 0.001 0.96(0.86-1.07) 0.46 0.97(0.87-1.08) 0.59 0.96(0.87-1.06) 0.44 LAA dense SEC/thrombus 3.12(1.39-6.99) 0.006 2.02(0.75-5.45) 0.167 LAA MD 1.19(1.09-1.29) &lt;0.001 1.19(1.08-1.31) 0.001 1.19(1.08-1.31) 0.001 1.19(1.08-1.31) 0.001 Univariable and multivariable logistic regression analyses of associations between clinical and echocardiographic covariates with stroke Abstract Figure.

scholarly journals Atrial performance in healthy subjects following high altitude exposure at 4100 m: 2D speckle-tracking strain analysis

2021 ◽  
Author(s):  
Chunyan He ◽  
Chuan Liu ◽  
Shiyong Yu ◽  
Jie Yang ◽  
Xiaohan Ding ◽  
...  
Keyword(s):  
High Altitude ◽  
Speckle Tracking ◽  
Contractile Function ◽  
Strain Analysis ◽  
Atrial Function ◽  
Peak Strain ◽  
Short Term ◽  
Atrial Contraction ◽  
2D Speckle Tracking ◽  
Ventricular Filling

AbstractHigh altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is involved in ventricular passive filling, however the atrial performance to HA exposure is poorly understood. This study aimed to evaluate the effect of short-term HA exposure on bi-atrial function. Physiological and 2D-echocardiographic data were collected in 82 healthy men at sea level (SL, 400 m) and 4100 m after an ascent within 7 days. Atrial function was measured using volumetric and speckle-tracking analyses during reservoir, conduit and contractile phases of cardiac cycle. Following HA exposure, significant decreases of reservoir and conduit function indexes were observed in bi-atria, whereas decreases of contractile function indexes were observed in right atrium (RA), estimated via RA active emptying fraction (SL 41.7 ± 13.9% vs. HA 35.4 ± 12.2%, p = 0.001), strain during the contractile phase [SL 13.5 (11.4, 17.8) % vs. HA 12.3 (9.3, 15.9) %, p = 0.003], and peak strain rate during the contractile phase [SL − 1.76 (− 2.24, − 1.48) s−1 vs. HA − 1.57 (− 2.01, − 1.23) s−1, p = 0.002], but not in left atrium (LA). In conclusion, short-term HA exposure of healthy individuals impairs bi-atrial performance, mostly observed in RA. Especially, atrial contractile function decreases in RA rather than LA, which seems not to compensate for decreased ventricular filling after HA exposure. Our findings may provide a novel evidence for right-sided heart dysfunction to HA exposure.

scholarly journals The predictive value of left atrial expansion index and left atrial contractile strain in younger hypertensive patients with atrial fibrillation

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
N Georgieva ◽  
E Kinova ◽  
A Borizanova - Petkova ◽  
B Krastev ◽  
A Goudev
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Social Impact ◽  
Contractile Function ◽  
Global Longitudinal Strain ◽  
Concomitant Disease ◽  
Hypertensive Patients ◽  
Functional Changes

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND   Arterial hypertension (HTN) is the most prevalent risk factor for Atrial fibrillation (AF) through structural and functional changes of the left atrium. Paroxysmal AF is mainly asymptomatic and silent forms in patients with HTN are associated with thromboembolic complications. However, prompt identification of HTN patients at risk for AF may be strategic for preventing purposes.  PURPOSE To assess sensitive and  predictive parameters for AF onset in HTN patients using two-dimensional (2D) conventional and speckle tracking echocardiography of the left atrium (LA) and left ventricle (LV).  METHODS A total of 165 consecutive patients were screened for participation in the study.  Only 80 patients met the inclusion criteria ( age below 60 years; with well controlled HTN or HTN with AF; without concomitant disease or other risk factors for AF).They were separated in two groups: 43 with HTN and 37 patients with AF and HTN. All patients underwent standard 2D echocardiography with volumetric and Speckle tracking analysis for assessment of: LV global longitudinal strain; LA total ( LATEF), passive ( LAPEF), active (LAAEF) emptying fractions; LA stiffness and expansion index; LA - reservoir (LASr), conduit (LAScd) and contractile (LASct) strain.  RESULTS There were statistically significant differences between patents with HTN and  HTN with AF group in: LASr (30.88 ± 3.99% vs. 27.89 ± 8.21 %, p= 0.049), LASct (-17.64 ± 2.04% vs. -14.4 ± 6.74 %, p= 0.007) and LA expansion index (122 ± 42% vs. 174 ± 115%; p = 0.014). There were no significant differences in other LV and LA structural and functional indices. Multiple regression analysis demonstrated that  LASct ( B= - 0.043’ p= 0.001; 95%CI -0.063- -0.023) and expansion index (B= 0.023; p= 0.001, 95%CI 0.117- 0.349)  are independent predictors of AF in hypertensive patients.  Conclusion Preserved LA compliance and contractile function are essential for maintenance of sinus rhythm in younger HTN patients. These findings could be used for  prediction of cardiovascular events and preventing AF onset in younger hypertensive population with a huge social impact.

scholarly journals Left atrial function after successful catheter ablation for paroxysmal atrial fibrillation: cryoablation versus radiofrequency techniques

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Pilichowska ◽  
A Sikorska ◽  
J Baran ◽  
R Piotrowski ◽  
T Krynski ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Paroxysmal Atrial Fibrillation ◽  
Left Atrial ◽  
Speckle Tracking ◽  
The Body ◽  
P Value ◽  
Rf Ablation ◽  
Funding Sources ◽  
Baseline Values ◽  
Funding Acknowledgements

Abstract Funding Acknowledgements Type of funding sources: None. Purpose It has been suggested that cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF) may lead to more extensive left atrial (LA) injury than radiofrequency (RF) ablation, however, results are conflicting. We sought to address this issue using modern echocardiographic techniques. Methods We performed transthoracic echocardiography in 90 patients (66% males, mean age 57 ± 10 years) successfully treated  with RF (51%) or CB (49%) ablation for PAF before and 6 months after the procedure. Peak longitudinal LA strain (LAS) and strain rate (LASR) during the reservoir (r), conduit (cd) and contraction (ct) phases were measured during sinus rhythm by speckle tracking. The LA diameter and volume (LAV) index - using biplane area-length method divided by the body surface area were also calculated. Results The LA diameter decreased (38.1 ± 4.0 vs 37.2 ± 3.8 mm, p = 0.004), the LAV index did not change (33.5 ± 11.9 vs 34.4 ± 8.9 mL/m², p = 0.272) at 6 months in the whole study group. The LASRr and LASRcd increased, whereas there were no changes in remaining LA function parameters in either ablation strategy (table). The CB subgroup did not differ in LA function parameters comparing to RF subgroup at six months after procedure (table). Conclusion CB and RF ablation did not differentially affect the LA function. Successful ablation for PAF resulted in improvement of  rate of deformation during reservoir and conduit LA cycle and stable contractile LA function. LA function parameters RF N = 46 (51%) CB N = 44 (49%) 6 months RF vs CB Parameter Baseline 6 months p Baseline 6 months p p* Global LASr [%] 27.7 ± 6.35 27.9 ± 6.0 0.833 27.9 ± 7.2 27.0 ± 6.4 0.370 0.539 Global LAScd [%] -14.6 ± 4.1 -14.8 ± 4.6 0.761 -15.3 ± 5.3 -14.1 ± 3.2 0.080 0.399 Global LASct [%] -13.0 ± 4.84 -13.0 ± 3.20 1.00 -12.6 ± 3.81 -12.9 ± 4.18 0.629 0.897 Global LASRr [sˉ&sup1;] 1.18 ± 0.22 1.27 ± 0.26 0.046 1.07 ± 0.27 1.18 ± 0.30 0.041 0.141 Global LASRcd [sˉ&sup1;] -1.11 ± 0.33 -1.25 ± 0.35 0.013 -1.07 ± 0.31 -1.16 ± 0.30 0.044 0.214 Global LASRct [sˉ&sup1;] -1.46 ± 0.40 -1.50 ± 0.31 0.500 -1.42 ± 0.51 -1.39 ± 0.42 0.742 0.187 *p value corrected for baseline values

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