Layer-specific Longitudinal Strain Research Articles

The clinical application of longitudinal layer specific strain as a diagnostic and prognostic instrument in ischemic heart diseases: A systematic review and meta-analysis.

2-dimensional Speckle-Tracking Echocardiography, to obtain longitudinal layer specific strain (LSS), has recently emerged as a novel and accurate non-invasive imaging technique for diagnosis as well as for prediction of adverse cardiac events. This systematic review and meta-analysis aimed to give an overview of the possible clinical implication and significance of longitudinal LSS. We conducted a systematic review and meta-analysis with all the studies involving layer specific strain in patients with ischemic heart disease (IHD). Of 40 eligible studies, 9 met our inclusion criteria. Studies that were included either investigated the prognostic value (n = 3) or the diagnostic value (n = 6) of longitudinal LSS. The pooled meta-analysis showed that longitudinal LSS is a significant diagnostic marker for coronary artery disease (CAD) in patients with IHD. Endocardial LSS was found to be a good diagnostic marker for CAD in IHD patients (OR: 1.28, CI95% [1.11-1.48], p < 0.001, per 1% decrease). Epicardial (OR: 1.34, CI95% [1.14-1.56], p < 0.001, per 1% decrease), Mid-Myocardial (OR: 1.24, CI95% [1.12-1.38], p < 0.001, per 1% decrease) and endocardial (OR: 1.21, CI95% [1.09-1.35], p < 0.001, per 1% decrease) LSS all entailed diagnostic information regarding CAD, with epicardial LSS emerging as the superior diagnostic marker for CAD in patients with SAP. Endocardial LSS proved to be the better diagnostic marker of CAD in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). LSS was shown to be a good prognostic maker of adverse cardiac events in IHD patients. Two studies found endocardial circumferential strain to be the good predictor of outcome in CAD patients and when added to baseline characteristics. Epicardial LSS emerged as best predictor in acute coronary syndrome (ACS) patients. In patients with SAP, epicardial LSS was the stronger diagnostic marker while in NSTE-ACS patients, endocardial LSS was the stronger diagnostic marker. In addition, endocardial circumferential strain is the better predictor of adverse outcome in CAD patients whilst in ACS patients, epicardial LSS was found to be a better predictor of outcome.

Endotrophin and matrix metalloproteinase-2 levels in bicuspid aortic valve and hypertension associated aortopathy and their relationship with strain parameters of the ascending aorta.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Ascending aorta dilatation is related to BAV- and hypertension (HTN)-associated aortopathy. The aim of this study was to investigate aortic elasticity, as well as aortic deformation of the ascending aorta, using strain imaging, and to evaluate the possible relationship of biomarkers, such as endotrophin and matrix metalloproteinase-2 (MMP-2), with ascending aorta dilatation in patients with BAV- or HTN-associated aortopathy. This prospective study included patients with ascending aorta dilatation with BAV (n = 33), or normal tricuspid aortic valve with HTN (n = 33), and 20 control subjects. The mean age of the total patients was 42.76 ± 10.4 years (67% male, 33% female). We calculated aortic elasticity parameters using the relevant formula by M-mode echocardiography and determined layer-specific longitudinal and transverse strains of the proximal aorta by speckle-tracking echocardiography. Blood samples of the participants were drawn for the analysis of endotrophin and MMP-2. Aortic strain and aortic distensibility were significantly decreased, whereas the aortic stiffness index was significantly increased in patient groups with BAV or HTN compared to the control group (p < 0.001). Moreover, longitudinal strain of both the anterior and posterior aortic walls of the proximal aorta were significantly impaired in BAV and HTN patients (p < 0.001). Serum endotrophin levels were significantly reduced in the patient cohort compared to the controls (p = 0.001). Endotrophin was noted to be significantly positively correlated with aortic strain and aortic distensibility (r = 0.37, p = 0.001; r = 0.45, p < 0.001, respectively), whereas inversely associated with aortic stiffness index (r = -0.402, p < 0.001). Furthermore, endotrophin was the single independent predictor of ascending aorta dilatation (OR = 0.986, p < 0.001). A cut-off value of endotrophin ≤ 82.38 ng/mL predicted ascending aorta dilatation with a sensitivity of 80.3% and specificity of 78.5% (p < 0.0001). The present study showed that aortic deformation parameters and elasticity are impaired in BAV and HTN patients, and strain imaging allows for a good analysis of ascending aorta deformation. Endotrophin could be a predictive biomarker of ascending aorta dilatation in BAV and HTN aortopathy.

Comparison of Myocardial Layer-Specific Strain and Global Myocardial Work Efficiency During Treadmill Exercise Stress in Detecting Significant Coronary Artery Disease.

BackgroundMyocardial layer-specific strain can identify myocardial ischemia. Global myocardial work efficiency (GWE) based on non-invasive left ventricular (LV) pressure-strain loops is a novel parameter to determine LV function considering afterload. The study aimed to compare the diagnostic value of GWE and myocardial layer-specific strain during treadmill exercise stress testing to detect significant coronary artery disease (CAD) with normal baseline wall motion.MethodsEighty-nine patients who referred for coronary angiography due to suspected of CAD were included. Forty patients with severe coronary artery stenosis were diagnosed with significant CAD, and 49 were defined as non-significant CAD. Stress echocardiography was performed 24 h before angiography. Layer-specific longitudinal strains were assessed from the endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Binary logistic regression analyses were performed to evaluate the association between significant CAD and echocardiographic parameters. A receiver operating characteristic curve was used to assess the capability of layer-specific strain and GWE to diagnose significant CAD.ResultsPatients with significant CAD had the worse function in all three myocardial layers at peak exercise compared with those with non-significant CAD when assessed with global longitudinal strain (GLS). At the peak exercise and recovery periods, GWE was lower in patients with significant CAD than in patients with non-significant CAD. In multivariable binary logistic regression analysis, peak endocardial GLS (OR: 1.35, p = 0.006) and peak GWE (OR: 0.76, p = 0.001) were associated with significant CAD. Receiver operating characteristic curves showed peak GWE to be superior to mid-myocardial, epicardial, and endocardial GLS in identifying significant CAD. Further, adding peak GWE to endocardial GLS could improve diagnostic capabilities.ConclusionsBoth GWE and endocardial GLS contribute to improving the diagnostic performance of exercise stress echocardiography. Furthermore, adding peak GWE to peak endocardial GLS provides incremental diagnostic value during a non-invasive screening of significant CAD before radioactive or invasive examinations.

Layer-specific longitudinal strain detects transmural dysfunction in chronic severe aortic regurgitation before and after aortic valve surgery.

To assess if layer-specific longitudinal strain (LS) provides incremental diagnostic and prognostic value compared to global longitudinal strain (GLS) in patients with chronic severe aortic regurgitation (AR) scheduled for aortic valvesurgery. Forty-one patients were examined with speckle tracking echocardiography before surgeryalong with 15 healthy age-matched controls. Paired strain analyses before and after surgery were available in 31 patients. Layer-specific LS analysis enabled assessment of epicardial GLS (GLSepi), endocardial GLS (GLSendo), and conventional GLS. Strain parameters were indexed to end-diastolic volume (EDV; GLS/EDV) to account for increased preload. The prognostic value of layer-specific LS was evaluated using the primary outcome of persistent LV dilatation (LVEDV ≥ 175mL) three months after surgery. Absolute (GLS, GLSepi, GLSendo) and EDV-indexed layer-specific LS (GLS/EDV, GLSepi/EDV, GLSendo/EDV) were impaired in severe AR compared to controls at baseline (GLS:17.0 ± 3.2 vs. 20.6 ± 2.0; GLSepi:14.6 ± 2.8 vs. 18.1 ± 1.9; GLSendo:20.2 ± 3.7 vs. 23.8 ± 2.2%; GLS/EDV:0.09 ± 0.05 vs. 0.21 ± 0.05; GLSepi/EDV:0.08 ± 0.04 vs. 0.18 ± 0.04; GLSendo/EDV:0.11 ± 0.06 vs. 0.24 ± 0.05%/mL; all p < 0.001). In severe AR, GLS, GLSepi and GLSendo decreased after surgery whereas GLS/EDV, GLSepi/EDV and GLSendo/EDV increased (all p < 0.001). Impaired absolute and EDV-indexed layer-specific LS were all associated with the primary outcome (all p ≤ 0.01). Area under the curve analysis revealed similar prognostic value of GLSepi, GLSendo and GLS (GLS:0.86; GLSepi:0.87; GLSendo:0.86; p = n.s.). EDV-indexed LS did not improve the predictive value significantly (GLS/EDV:0.93; GLSepi/EDV: 0.93; GLSendo/EDV:0.92; p = n.s.). Layer-specific LS detects transmural dysfunction in chronic severe AR and predicts persistent LV dilation after surgery. Layer-specific LS or EDV-indexed LS does not provide incremental prognostic value compared to conventional GLS.

Global myocardial work: A new way to detect subclinical myocardial dysfunction with normal left ventricle ejection fraction in essential hypertension patients: Compared with myocardial layer-specific strain analysis.

The aim of this study was to determine whether global myocardial work (MW), derived from non-invasive left ventricle (LV) pressure-strain loops (PSL) at rest, could predict subclinical LV myocardial dysfunction in preserved left ventricular ejection fraction (LVEF) essential hypertension (EHT) patients. A total of 105 untreated EHT patients and 55 normal controls were enrolled in this study. Apical 4-, 3- and 2-chamber views were acquired by two-dimensional echocardiography. The peak systolic myocardial layer-specific longitudinal strain (epimyocardial: GLSEpi; middle layer: GLSMid; and endomyocardial: GLSEndo), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and myocardial work efficiency (GWE) were generated by speckle-tracking echocardiography (STE). The values of GLSEpi, GLSMid, and GLSEndo were significantly lower in EHT patients with LVH than in EHT patients without LVH and normal controls. GWW was significantly increased in EHT patients with LVH compared with without LVH and normal subjects, while GWE was significantly reduced in EHT patients with LVH compared with without LVH and normal subjects. ROC analysis showed that combined global MW values were a more sensitive predictor for detecting the accuracy of LV subclinical dysfunction in EHT patients than layer-specific GLS. From the research, we conclude that global MW is more sensitive to layer-specific GLS in its ability to detect subclinical LV dysfunction even in EHT patients even without LVH.

The impact of chronic alcohol overuse on heart function and prognosis: layer-specific longitudinal strain and mid-term outcome analysis.

The exact effects of alcohol drinking on cardiac function are not clear. This study aimed to determine the relationship between consumed amount of alcohol, myocardial injury, and prognosis. Myocardial function and cardiac outcomes were examined in subjects with chronic alcoholism by classical and strain echocardiographic parameters, including global (GLS) and layer-specific longitudinal strain of the endocardial (GLSendo) and epicardial (GLSepi) layer. One group of 65 alcohol-overusers (ALC), median (IQR, interquartile range) age 44 (38-51) years, was compared with 30 controls (CG). Median (IQR) alcohol dose (in alcohol units, 1 AU = 1 g of ethanol) per week was 30 (12-51) AU in ALC and 0 in CG; P <0.001, and the mean (SD, standard deviation) drinking period was 16 (9) years. ALC patients demonstrated higher left ventricular (LV) mass and impaired diastolic function. The ALC group demonstrated lower median (IQR) LV ejection fraction (EF): 52% (37%-57%) vs 60% (55%-63%) (P <0.001); GLS: 17% (9%-20%) vs 19% (18%-21%) (P = 0.01); absolute layer-specific strain values. GLSendo <19% and GLSepi <15% predicted worsened mid-term prognosis, as did elevated N-terminal brain natriuretic peptide (NT-proBNP) and lower EF and GLS. Long-term alcohol overuse, even with a rather low reported median (IQR) dose of 4 (2-7) AU per day resulted in LV hypertrophy, diastolic and systolic dysfunction. Diminished GLS <18%, endocardial <19% and epicardial <15% layer strain predicted combined endpoints but did not significantly improve the prognostic power of tested models, based on NT-proBNP and EF in follow-up.

Age- and sex-based normal values of layer-specific longitudinal and circumferential strain by speckle tracking echocardiography: the Copenhagen City Heart Study.

Technical advancements in 2D-speckle tracking echocardiography (2DSTE) have allowed for quantification of layer-specific global longitudinal strain (GLS) and circumferential strain (GCS) of the left ventricle (LV). The aim of this study was to establish age- and sex-based reference ranges of peak systolic layer-specific GLS and GCS and to assess normal values of regional strain. We performed 2DSTE analysis of 1997 members of the general population from the fifth round of the Copenhagen City Heart Study, who were free of cardiovascular disease and risk factors. The mean age was 46 ± 16 years (range 21-97) and 62% were female. Mean values for peak systolic whole wall GLS (GLSWW.Sys), endomycardial (GLSEndo.Sys), and epimyocardial (GLSEpi.Sys) were 19.9 ± 2.1% (prediction interval [PI]: 15.8-24.0%), 23.5 ± 2.5% (PI: 18.6-28.4%), and 17.3 ± 1.9% (PI: 13.6-21.1%), respectively. Mean peak systolic whole wall GCS (GCSWW.Sys), was 21.6 ± 3.7% (PI: 14.3-28.9%), endomyocardial (GCSEndo.Sys) was 31.9 ± 4.7% (PI: 22.7-41.1%), and epimyocardial (GCSEpi.Sys) was 14.3 ± 3.8% (PI: 6.8-21.8%). A significant discrepancy in normal strain values between males and females was observed. Men had lower mean values and lower reference limits for all strain parameters. Furthermore, GLS and GCS changed differently with age in males and females. Finally, regional LS decreased from the apical to the basal LV region in both sexes, and regional CS varied significantly by LV segment. In this study, we reported age- and sex-based reference ranges of layer-specific GLS and GCS. These reference ranges varied significantly with sex and age.

Single systemic right ventricle longitudinal strain: Intravendor reproducibility and intervendor agreement in children.

Strain derived from speckle-tracking echocardiography is emerging as a useful tool in the assessment of single ventricle function. The purpose of this study is to compare layer-specific longitudinal strain values in children with single, systemic right ventricles (sRV) using two commercially available software platforms (GE EchoPAC (EP) and TomTec (TT)). Two readers analyzed two-dimensional longitudinal strain on EP (v 202) and TT (v 2.21.25) in 40 pediatric sRV patients. Intravendor reproducibility and intervendor agreement between layer-specific measurements were assessed by intraclass correlation coefficient and Bland-Altman analysis. Absolute difference (AbΔ) and relative mean errors (RME) were calculated. Subgroup comparisons (stratified by age, heart rate (HR), and frames per second (FPS): HR ratio) were made. Median age was 4.4years. 32 (80%) patients had hypoplastic left heart syndrome; 19 (48%) were post-Fontan. Intravendor reproducibility was excellent with high ICC (0.86-0.97). AbΔ between readers was small (1.2%-1.5%) with interobserver RME slightly higher for TT (11%-12% vs 8%-9% for EP). Layer-specific intervendor agreement was poor (ICC 0.45-0.62). Default layer comparisons (EP mid vs TT endo) showed good agreement (ICC 0.72-0.77) and less variability (AbΔ 2%, RME 15%) than layer-to-layer. There were no differences in ICC for groups dichotomized by age, HR, or FPS:HR ratio. sRV strain values are more negative when using EP. Intravendor reproducibility for sRV peak longitudinal strain in children is excellent with acceptable variability between experienced users. Intervendor, layer-specific strain agreement is poor. Vendor default layer strain values show better agreement but are not interchangeable.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<−21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (−13.7% ± 3.4% vs. −17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = −0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = −0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Layer-Specific Strain Is Preload Dependent: Comparison between Speckle-Tracking Echocardiography and Cardiac Magnetic Resonance Feature-Tracking

Speckle-tracking echocardiographic (STE) imaging and cardiac magnetic resonance feature-tracking (CMR-FT) are novel imaging techniques enabling layer-specific quantification of myocardial deformation. Conventional echocardiographic parameters are load dependent, but few studies have investigated the effects of loading conditions on STE and CMR-FT layer-specific strain and the interchangeability of the two modalities. The aim of this study was to evaluate the effects of acute preload augmentation by saline infusion on STE and CMR-FT longitudinal and circumferential layer-specific strain parameters and their intermodal agreement. A total of 80 subjects, including 41 control subjects (mean age, 40±12years; 49% men) and 39 patients with cardiac disease (mean age, 47±15years; 92% men) were examined using STE and CMR-FT layer-specific strain analysis before and after saline infusion (median, 2.0L) with quantification of transmural global longitudinal strain (GLS), epicardial GLS, endocardial GLS, transmural global circumferential strain (GCS), epicardial GCS, and endocardial GCS in addition to epicardial-endocardial gradients. Bland-Altman plots and Pearson correlation coefficients were used to evaluate agreement between the two modalities across all strain parameters. Acute saline infusion increased all STE and CMR-FT layer-specific strain parameters in both groups. STE and CMR-FT GLS increased by 1.4±1.5% and 1.5±2.0% (P<.001) in control subjects and by 0.9±1.8% and 0.9±1.9% (P<.001) in patients with cardiac disease. STE and CMR-FT GCS increased by 2.0±2.2% and 1.8±2.3% (P<.001) in control subjects and by 1.8±2.3% and 1.7±3.6% in patients with cardiac disease (P<.001 and P=.03). STE longitudinal strain correlated strongly with corresponding CMR-FT longitudinal strain (GLS, epicardial GLS, and endocardial GLS: r=0.81, r=0.82, and r=0.81, respectively) despite poor intermodal agreement (bias±limits of agreement, -2.84±4.06%, 0.16±3.68%, and 2.33±3.52%, respectively) whereas GCS, epicardial GCS, and endocardial GCS correlated weakly between the two modalities (r=0.28, r=0.19, and r=0.34, respectively) and displayed poor intermodal agreement (bias±limits of agreement, -1.33±6.86%, 4.43±6.49%, and -9.92±8.55%, respectively). STE and CMR-FT longitudinal and circumferential layer-specific strain parameters are preload dependent in both control subjects and patients with cardiac disease. STE and CMR-FT longitudinal layer-specific strain parameters are strongly correlated, whereas circumferential layer-specific strain parameters are weakly correlated. STE and CMR-FT longitudinal and circumferential strain should not be used interchangeably, because of poor intermodal agreement.

Layer-specific strain for assessing the effect of naringin on systolic myocardial dysfunction induced by sepsis and its underlying mechanisms.

ObjectiveThis study aimed to investigate the protective effects of naringin on myocardial deformation and oxidative responses in rats with sepsis-induced myocardial dysfunction (SIMD).MethodsGlobal and segmental layer-specific longitudinal strain (LS) was assessed by speckle tracking echocardiography. Serum levels of creatine kinase, lactate dehydrogenase, superoxide dismutase, and malondialdehyde were measured. The activity of cleaved caspase-3 was determined by immunohistochemistry. Protein expression levels of Kelch-like ECH-related protein 1 (Keap1), nuclear erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were measured by western blotting.ResultsNaringin inhibited the lipopolysaccharide-induced decrease in global and layer-specific LS of the left ventricle. Naringin also increased superoxide dismutase expression and decreased malondialdehyde, creatine kinase, lactate dehydrogenase, and cleaved caspase-3 expression in rats with SIMD. Furthermore, naringin increased Nrf2 and HO-1 protein expression levels, and decreased Keap1 protein expression levels in rats with SIMD.ConclusionLayer-specific LS analysis of myocardial function by speckle tracking echocardiography can reflect early changes in myocardial systolic function. Naringin may possess a protective effect through moderating lipopolysaccharide-induced myocardial oxidative stress via the Keap1/Nrf2/HO-1 pathway in rats with SIMD.

Decreased layer specific longitudinal strain in myocardial segments supplied by stenosed LAD coronary artery: analysis for baseline, peak and recovery phase of stress echocardiography

Abstract Background Despite wide utility of global longitudinal strain in the assessment of left ventricular function up to now little is known about layer specific quantification of myocardial function during stress tests and its potential for ischemia detection. Purpose To investigate diagnostic utility of layer specific LS during stress echocardiography using marker segments in patients with established Left Anterior Descending (LAD) coronary artery status. Methods We retrospectively analyzed 63 patients (mean age 62.5±9.9 years, 62% males) with suspected coronary artery disease, who had performed dobutamine stress echocardiography (DSE). Layer specific speckle tracking LS analyses were performed during rest, maximal stress and recovery. As a marker for LAD (segment most probably supplied by this artery) we used mid-anterior left ventricle segments. LAD status were established with coronary angiography or angioCT and consider as significant if ≥70% stenosis was present. Results In our study group 14 patients had significantly stenosed LAD (group 1) and 24 had normal coronaries (group 2). We detected significantly lowered absolute values of strain in endocardial and mid-myocardial layers of segments supplied by stenosed LAD at rest for endocardium −8.6% (group 1) vs −13.4% (group 2); p=0.045; and mid-myocardium −7.3% (group 1) vs −11.2% (group 2); p=0.044. Moreover, we observed similar trend at recovery, however without reaching statistical significance. Conclusions Longitudinal strain analysis focused on segments supplied by assessed coronary artery my provide quantitative data confirming ischemia in the settings of rest and stress echocardiography. Our pilot study suggest that for inotropic agents like dobutamine the potential ischemic dysfunction may be however masked at peak stage of the test. Funding Acknowledgement Type of funding source: None

Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test &amp;lt;0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p&amp;lt;0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p&amp;lt;0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p&amp;lt;0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

Exercise echocardiography demonstrates potential myocardial damage in patients with repaired tetralogy of Fallot using layer-specific strain analysis.

Exercise stress echocardiography and layer-specific strains are emerging as important tools for cardiac assessment. This study was aimed to evaluate layer-specific strains and torsion parameters during exercise in order to investigate the characteristics of cardiac dysfunction in patients with repaired tetralogy of Fallot and to detect subclinical left ventricular dysfunction. Thirteen patients with repaired tetralogy of Fallot (median age, 17.3 [interquartile range, 14.5-22.9] years; 6 males) and 13 controls (median age, 28.5 [interquartile range, 27.6-31.6] years; 13 males) underwent echocardiography at rest and during supine exercise. Layer-specific longitudinal strain and circumferential strain of three myocardial layers (endocardium, midmyocardium, and epicardium), torsion, and untwisting rate were measured using two-dimensional speckle-tracking echocardiography. Peak endocardial papillary circumferential strain (-21.1 ± 2.6% vs. -25.8 ± 3.8%, p = 0.007), midmyocardial apical circumferential strain (-11.1 ± 4.0% vs. -15.6 ± 3.2%, p = 0.001), epicardial apical circumferential strain (-11.1 ± 4.0% vs. -15.6 ± 3.2%, p = 0.021), and torsion (8.9 ± 6.0 vs. 14.9 ± 4.8 degree, p = 0.021) were significantly lower in the repaired tetralogy of Fallot group than in the control group during exercise, though no significant difference was found between patients and controls at rest. Analysis of layer-specific strains and torsion parameters during exercise could detect subclinical left ventricular dysfunction in patients with repaired tetralogy of Fallot, which might reflect potential myocardial damage, at a stage where these parameters have normal values at rest. This finding provides new insight into the mechanisms of cardiac dysfunction in patients with repaired tetralogy of Fallot.

P678 Late gadolinium enhancement cardiac magnetic resonance and layer-specific longitudinal strain in treatment naive Anderson Fabry disease

Abstract Background In Anderson-Fabry disease (AFD), the accumulation of glycosphingolipids in cardiomyocytes causes inflammation, hypertrophy and interstitial fibrosis which is first limited to the mid-myocardial layers, then spreads to transmural fibrosis. Speckle tracking echocardiography allows the estimation of layer-specific strain, differentiating longitudinal strain (LS) at subendocardium and subepicardium (LSsubendo and LSsubepi, respectively). Purpose To investigate the matching of functional and structural abnormalities in newly diagnosed, never treated AFD patients by comparing multi-layer LS and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). Methods Twenty newly diagnosed, never treated AFD patients (age = 37 ± 13 years; F/M =10/10) and 20 healthy controls, matched for age and sex, underwent comprehensive evaluation of target organs and a standard echo-Doppler exam, including assessment of relative diastolic wall thickness (RWT) and left ventricular mass index (LVMI). Left ventricular hypertrophy (LVH) was defined as LVMi &amp;gt; 47 g/m^2.7 in women and &amp;gt;50 g/m^2.7 in men. Speckle tracking echocardiography derived left ventricular transmural global longitudinal strain (GLS), LSsubendo, LSsubepi and LS gradient (LSsubendo - LSsubpepi) were also determined. CMR sequences including assessment of LGE were also performed. Results AFD patients had normal renal function and comparable body mass index, blood pressure, heart rate, ejection fraction and diastolic indices with healthy controls. LVMi (p = 0.006) and RWT (p &amp;lt; 0.02) were greater in AFD patients than in controls. GLS (p = 0.006), LSsubendo (p = 0.005) and LSsubepi (p &amp;lt; 0.001) were lower in AFD patients. By CMR, only four patients (F/M = 3/1), 3 with LVH (75%), exhibited focal LGE, always localized in the midwall. LGE was detected at basal lateral wall in three patients and at the septal insertional points with the right ventricle in the remaining one. AFD patients with LGE had higher LVMi than those without LGE (47.2 ± 11.0 vs. 34.5 ± 11.6 g/m^2.7, p = 0.04). There was no correspondence of LGE with both regional LS and layer specific LS impairment (Figure). However, AFD patients with LGE had higher LS gradient compared to those without LGE (5.8 ± 0.65 vs. 4.8 ± 0.66, p &amp;lt; 0.02). Conclusions Treatment naïve AFD patients show a reduction of longitudinal deformation, which involves both subendocardial and subepicardial layers. Patients with LGE present higher LV mass and increased LS gradient, without a correspondence of LGE with both regional and layer specific LS impairment. Accordingly, this impairment might due to myocardial inflammation occurring in the early disease stages more than to myocardial fibrosis itself. Abstract P678 Figure. Multilayer bull"s eye and LGE-CMR in AFD

P1771 Gender differences of the blood pressure effects on early changes of left ventricle mechanics in untreated hypertension

Abstract Background Left ventricular (LV) diastolic dyssynchrony and global and layer-specific strain can be used for evaluation of early myocardial changes in hypertension. We tried to investigate the gender differences in these early changes in untreated uncomplicated hypertension. Methods This study included 43 consecutive patients (mean age 51.3 ±12.5 years, 56% men) with newly diagnosed hypertension from an out-patient clinic. All subjects were free of complications including renal dysfunction, LV hypertrophy, and diabetes. Comprehensive transthoracic echocardiography (E9, GE, USA) was conducted before treatment of hypertension. Diastolic and systolic parameters were measured by two-dimension (2D), Doppler, tissue Doppler imaging and 2D speckle tracking echocardiography (STE). The time-to-peak early diastolic myocardial annulus velocity (Te) at 6 LV segments from apical-4-chamber, apical-2-chamber and apical-3-chamber views were measured with reference to the QRS complex. The time to peak early diastolic strain rate (TDSr), global longitudinal strain (GLS), layer-specific longitudinal strain included sub-epicardial strain (EpiLS) and sub-endocardial strain (EndLS) were measured from 18 LV segments by STE. Diastolic dyssynchrony parameters were defined as the standard deviation (SD) of Te of all LV segments (Te-SD), SD of TDSr of 18 LV segments (TDSr-SD), and the maximal difference between any two TDSr of the 18 LV segments (MaxD-TDSr). Results There were no differences between men (56%) and women (44%) regarding age, initial blood pressure, hypertension duration, LV mass index, LV ejection fraction, and early mitral velocity to average early annulus velocity ratio. Regarding diastolic dyssynchrony parameters, men were significantly higher than women including Te-SD (22.3 ± 13.8 vs. 14.7 ± 4.2 ms; p = 0.016), TDSrSD (46.0 ± 13.3 vs. 35.3 ± 11.4 ±ms; p = 0.008), and MaxD-TDSr (162.0 ± 40.3 vs. 128.1 ± 50.7 ms; p = 0.019). Men also had worse GLS (-17.6 ± 1.9 vs. -19.5 ± 2.5 %; p = 0.007), EpiLS (-15.1 ± 1.7 vs. -17.0 ± 2.3, p = 0.003), and EndLS (-20.5 ± 2.2 vs. -22.4 ± 2.8 %; p = 0.018) than women. After multivariate analysis controlling age, systolic blood pressure, and LV mass index, TeSD (p = 0.039), TDSrSD (p = 0.018), MaxD-TDSr (p = 0.035) were still significantly higher than women. GLS (p = 0.046), and EpiLS (p = 0.025) were still worse in men. Conclusion In the same age, blood pressure, hypertension duration and LV mass index, men have more diastolic dyssynchrony and worse myocardial strain in untreated hypertension.

P1542 Reference values for multilayer longitudinal strain in children: preliminary findings from healthy individuals

Abstract BACKGROUND Strain echocardiography is a reliable echocardiographic modality to measure myocardial mechanical deformation and evaluate regional and global myocardial systolic function, and has been demonstrated to be a useful tool for the evaluation of cardiac function in children with acquired and congenital heart diseases. Recent advancements in echocardiographic technology allow to analyze myocardial strain in multiple layers. To our knowledge, there are no published reference values for echocardiographic multilayer-specific strain measurement. AIM OF THE STUDY Aim of our study was to establish normal reference values for left ventricular (LV) and right ventricular (RV) longitudinal strain (LS) in a wide population of Italian children and to provide normal reference values of layer-specific LS in a healthy pediatric population. METHODS AND RESULT At present we have analyzed data from two-hundred (target: n = 500) healthy, consecutive subjects (age &amp;lt;18 years, mean age 7.5 ± 4yrs; range from 1 month to 17,5 years). All subjects underwent a clinical cardiological evaluation including ECG and physical examination. Subsequently, a complete echo Doppler examination including LS evaluation using speckle-tracking echocardiography was performed. Individuals were excluded if any significant abnormality was found at echocardiography (e.g. valvular regurgitation more than trivial, any structural abnormalities including small ASDs or VSDs; patients with isolated PFO were included). Subendocardial, midwall, subepicardial LS, and strain gradient (LSsubepi - LSsubendo) were also determined. LS% analysis was considered acceptable if missing data were present in no more than one segment per echocardiographic view, according to current consensus. Echocardiographic yield for LS analysis was 98.5 % for 4-chamber views, 82.5% for 2-chamber views and 84.5% for 3-chamber views. Accordingly Global Longitudinal Strain (GLS) was available overall in 82% of the population analyzed so far (n= 164 children) on all layers, with a total of 8,872 echocardiographic available segments analyzed. Normal distribution was found for global subendocardial, midwall and subepicardial LS. As displayed in figure 1 (panels A-B-C), means ± SD were -20.8 ± 1.9% for LSsubendo, -19.2 ± 1.8% for LSsubepi and -19.9 ± 1.8% for LSmidwall. Accordingly higher value (95ile) for normal LS were -17.9%, -16.4% and -17.1% for LSsubepi, LSsubendo and LSmidwall, respectively. A significant subepicardial to subendocardial gradient was found in all children with higher absolute values found at the endocardial level, with a mean difference of 1.6 ± 0.9% (Panel D). CONCLUSIONS We provide preliminary data on 200 children to establish normal reference values for echocardiographic multilayer-specific strain measurement in a wide population of healthy italian children. Abstract P1542 Figure.

Temporal echocardiography findings in patients with fulminant myocarditis: beyond ejection fraction decline.

The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients. In this study, changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored. We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment. Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled. Conventional echocardiographic measurements were obtained, and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%). Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified, and their changes with time were monitored in 14 FM patients. All patients had severely impaired cardiac function. Steep improvement in LVEF and GLS were observed within 6 days. Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal. In conclusion, FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days. The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.

P4348Early assessment of left ventricular function by layer-specific strain and its relationship to pulsatile arterial load in patients with coronary slow flow

Abstract Background Previous studies reported controversial Left ventricular (LV) function impairment and pathophysiology in patients with coronary slow flow (CSF). Greater arterial load has been shown to increase aortic impedance and endothelial shear stress, potentially affecting coronary anatomy and function. We investigated LV systolic function by a new layer-specific strain technology and assessed the association between pulsatile arterial load and contractility. Methods and results A total of 70 patients with CSF and 50 controls with normal coronary angiography were included in the study. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium and epicardium (GLS-endo, GLS-mid, GLS-epi and GCS-endo, GCS-mid, GCS-epi) by two-dimensional speckle tracking imaging (2D-STI). Pulsatile arterial load was estimated by indexed arterial compliance (ACI). Layer-specific GLS showed a decreasing gradient from the endocardium to the epicardium in both controls and CSF group. GLS-endo and GLS-mid in CSF group were significantly lower than the control group (all P&lt;0.05). Layer-specific longitudinal strain showed a good correlation with the number of affected coronary arteries (all P&lt;0.05) and the mean thrombolysis in myocardial infarction frame count (TFC) (all P&lt;0.05). ACI was lower in CSF patients (P=0.005) and ACI was correlated negatively with layer-specific GLS (all P&lt;0.05). Conclusion Layer-specific evaluation of the LV provides an understanding of the layer-specific properties of the LV wall and the possible process of the LV impairment in patients with CSF. Greater pulsatile arterial load, as manifested by a lower ACI, is coupled with worse LV longitudinal function in CSF patients.

P3371Impact of severe aortic stenosis on layer-specific longitudinal strain and its prognostic value

Abstract Background Global longitudinal strain (GLS) was used to detect early myocardial dysfunction in patients with aortic stenosis (AS), however few data are currently available on the different susceptibility of specific myocardial layer to increased wall stress and its prognostic role. The present study sought to investigate the relationship between changes in LV multilayer strain and the clinical outcome of patients with severe AS and preserved left ventricle ejection fraction (LVEF). Methods We included in the analysis 211 patients (56% males, mean age 73±12 years old) with severe AS and LVEF≥50%, divided in symptomatic (n=114) and asymptomatic group (n=97), and 50 controls matched for age and sex. Patients with moderate-to-severe concomitant valvulopathy and inadequate acoustic windows for evaluation by speckle tracking analysis were excluded. Clinical, demographic and resting echocardiographic data were recorded, including quantification of 2D GLS, subendocardial LS and subepicardial LS. Results Symptomatic patients had increased LV wall thickness and LV mass index than asymptomatic ones (p&lt;0.001), higher transaortic mean pressure gradients (48±14 vs 44±13 mmHg, p=0.004), and lower aortic valve areas (0.42±0.09 vs 0.45±0.08 cm2/m2, p&lt;0.017). GLS was significantly lower in patients with AS compared to controls, especially in symptomatic group (17.9±3.4 vs 19.1±3.1 vs 20.7±2.1%, p&lt;0.001 in symptomatic, asymptomatic and control groups respectively) suggesting an early, subtle, myocardial dysfunction. In particular, the analysis of layer-specific myocardial deformation revealed a marked difference in both the subendocardial LS (20.1±4.9 vs 21.7±4.2 vs 23.4±2.5%, p&lt;0.001) and subepicardial LS (15.8±3.1 vs 16.8±2.8 vs 18.3±1.8%, p&lt;0.001). At multivariable logistic regression analysis, subendocardial LS was independently associated to symptoms (OR=1.148, p=0.014), together with indexed left atrial volume (OR=1.035, p=0.007) and LV concentric remodelling (OR=2.429, p=0.031). During a mean follow up of 38 months (IQ range 18–60 months), 12 patients with asymptomatic severe AS had a cardiovascular (CV) death. The presence of a subendocardial LS &lt;22% at baseline was associated with a higher rate of CV events at 3 and 5-year follow-up (19% vs 5% at 3-year follow-up, and 22% vs 8% at 5-year follow-up, respectively; log-rank p=0.044). Conclusion In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease. In this setting, the subendocardial LS appears to be independently associated to symptoms than subepicardial LS. In asymptomatic patients, a reduced value of subendocardial LS is associated with higher CV mortality at 3- and 5-year follow-up.