Two-Dimensional Strain is more Precise than Conventional Measures of Left Ventricular Systolic Function in Pediatric Patients.

Ejection fraction (EF) and fractional shortening (FS) are standard methods of quantifying left ventricular (LV) systolic function. 2D global longitudinal strain (2D GLS) is a well-established, but underutilized method for LV function quantification. The aim of this study was to assess precision of GLS compared to EF & FS in pediatrics. Echocardiograms were prospectively analyzed by 2 blinded observers. FS, EF, and GLS were calculated following standard methods. Bland-Altman was applied to assess agreement. Intraclass correlation coefficient (ICC) was used to measure reliability. Coefficient of variation was used to demonstrate relative variability between methods. 103 pediatric echos were evaluated for inter-observer reproducibility, and 15 patients for intra-observer reproducibility. GLS had higher inter-observer agreement and reliability (bias 7%, 95% LOA - 3.4 to + 3.5, ICC 0.86 CI 0.80-0.90) compared to EF (bias 27%, 95% LOA - 18.9 to + 19.5; ICC 0.25 CI 0.07-0.43) and FS (bias 12%, 95% LOA - 11.9 to + 12.2; ICC 0.53 CI 0.38-0.66). GLS also had higher intra-observer agreement (bias 4%, 95% LOA - 3.6 to + 3.7; ICC 0.87 CI 0.66-0.96) compared to EF (bias 11%, 95% LOA - 14.9 to + 15.1; ICC 0.26 CI - 0.28-0.67) and FS (bias 12%, 95% LOA - 12.2 to + 12.5; ICC 0.38 CI - 0.15-0.74). GLS is a more precise method for quantifying LV function in pediatrics, with lower variability compared to EF and FS. GLS provides a more reliable evaluation of LV systolic function and should be utilized more widely in pediatrics.

Normal fetal cardiac deformation values in pregnancy; a prospective cohort study protocol.

BACKGROUND: Myocardial deformation imaging offers the potential to measure myocardial function. Remodelling, the change in size, shape and function, appears as a result of pressure or volume changes and is thought to be the first sign of fetal adaptation to placental dysfunction. Deformation can be measured using speckle tracking echocardiography (STE). STE in the fetus might be useful for detection and follow up of the fetus endangered by placental dysfunction. Reference values for fetal myocardial deformation during gestation have not been comprehensively described and need further investigation before STE can be introduced in daily clinical practice. The aim of this study is to determine reference values for fetal myocardial deformation throughout gestation in uncomplicated pregnancies. METHODS: A longitudinal cohort will be performed. 150 Women, pregnant from a non-anomalous singleton, will be included from 19 to 21 + 6 weeks gestational age. Thereafter, fetal heart ultrasounds will be performed 4 weekly, until 41 weeks gestational age or delivery. Ultrasound data will be analysed using STE software to determine reference values for fetal cardiac deformation during gestation. DISCUSSION: Measuring cardiac deformation changes in pregnancy can be a promising tool to detect preclinical cardiac adaptation to placental dysfunction. However, previous studies used different ultrasound scans and STE software resulting in incomparable and contradictory results on deformation values. In this prospective study reference values during pregnancy, cardiac deformation values will be assessed with the same ultrasound and software package in 150 uncomplicated pregnancies. TRIAL REGISTRATION: National Trial Register number: NTR7132. Date of inclusion: 2018/04/06.

Type I Diabetic Akita Mouse Model is Characterized by Abnormal Cardiac Deformation During Early Stages of Diabetic Cardiomyopathy with Speckle-Tracking Based Strain Imaging.

BACKGROUND/AIMS: Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. METHODS: Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. RESULTS: With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. CONCLUSIONS: We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.

Myocardial deformation assessed by longitudinal strain: Chamber specific normative data for CMR-feature tracking from the German competence network for congenital heart defects.

PURPOSE: Left ventricular two-dimensional global longitudinal strain (LS) is superior to ejection fraction (EF) as predictor of outcome. We provide reference data for atrial and ventricular global LS during childhood and adolescence by CMR feature tracking (FT). METHODS: We prospectively enrolled 115 healthy subjects (56 male, mean age 12.4 ± 4.1 years) at a single institution. CMR consisted of standard two-dimensional steady-state free-precession acquisitions. CMR-FT was performed on ventricular horizontal long-axis images for derivation of right and left atrial (RA, LA) and right and left ventricular (RV, LV) peak global LS. End-diastolic volumes (EDVs) and EF were measured. Correlations were explored for LS with age, EDV and EF of each chamber. RESULTS: Mean±SD of LS (%) for RA, RV, LA and LV were 26.56±10.2, -17.96±5.4, 26.45±10.6 and -17.47±5, respectively. There was a positive correlation of LS in LA, LV, RA and RV with corresponding EF (all P<0.05); correlations with age were weak. Gender-wise differences were not significant for atrial and ventricular LS, strain rate and displacement. Inter- and intra-observer comparisons showed moderate agreements. CONCLUSIONS: Chamber-specific nomograms for paediatric atrial and ventricular LS are provided to serve as clinical reference, and to facilitate CMR-based deformation research. KEY POINTS: • No normative data exist for CMR-derived global longitudinal strain in the young. • This prospective study provides reference data for atrial and ventricular longitudinal strain. • The data will serve as reference for CMR-based clinical and research use.

Cardiac dysfunction in cancer survivors unmasked during exercise.

BACKGROUND: The cardiac dysfunction associated with anthracycline-based chemotherapy cancer treatment can exist subclinically for decades before overt presentation. Stress echocardiography, the measurement of left ventricular (LV) deformation and arterial haemodynamic evaluation, has separately been used to identify subclinical cardiovascular (CV) dysfunction in several patient groups including those with hypertension and diabetes. The purpose of the present cross-sectional study was to determine whether the combination of these techniques could be used to improve the characterisation of subclinical CV dysfunction in long-term cancer survivors previously treated with anthracyclines. MATERIALS AND METHODS: Thirteen long-term cancer survivors (36 ± 10 years) with prior anthracycline exposure (11 ± 8 years posttreatment) and 13 age-matched controls were recruited. Left ventricular structure, function and deformation were assessed using echocardiography. Augmentation index was used to quantify arterial haemodynamic load and was measured using applanation tonometry. Measurements were taken at rest and during two stages of low-intensity incremental cycling. RESULTS: At rest, both groups had comparable global LV systolic, diastolic and arterial function (all P > 0·05); however, longitudinal deformation was significantly lower in cancer survivors (-18 ± 2 vs. -20 ± 2, P < 0·05). During exercise, this difference between groups persisted and further differences were uncovered with significantly lower apical circumferential deformation in the cancer survivors (-24 ± 5 vs. -29 ± 5, -29 ± 5 vs. 35 ± 8 for first and second stage of exercise respectively, both P < 0·05). CONCLUSION: In contrast to resting echocardiography, the measurement of LV deformation at rest and during exercise provides a more comprehensive characterisation of subclinical LV dysfunction. Larger studies are required to determine the clinical relevance of these preliminary findings.

Estimation of myocardial deformation using correlation image velocimetry.

BACKGROUND: Tagged Magnetic Resonance (tMR) imaging is a powerful technique for determining cardiovascular abnormalities. One of the reasons for tMR not being used in routine clinical practice is the lack of easy-to-use tools for image analysis and strain mapping. In this paper, we introduce a novel interdisciplinary method based on correlation image velocimetry (CIV) to estimate cardiac deformation and strain maps from tMR images. METHODS: CIV, a cross-correlation based pattern matching algorithm, analyses a pair of images to obtain the displacement field at sub-pixel accuracy with any desired spatial resolution. This first time application of CIV to tMR image analysis is implemented using an existing open source Matlab-based software called UVMAT. The method, which requires two main input parameters namely correlation box size (C B ) and search box size (S B ), is first validated using a synthetic grid image with grid sizes representative of typical tMR images. Phantom and patient images obtained from a Medical Imaging grand challenge dataset ( http://stacom.cardiacatlas.org/motion-tracking-challenge/ ) were then analysed to obtain cardiac displacement fields and strain maps. The results were then compared with estimates from Harmonic Phase analysis (HARP) technique. RESULTS: For a known displacement field imposed on both the synthetic grid image and the phantom image, CIV is accurate for 3-pixel and larger displacements on a 512 × 512 image with (C B ,S B )=(25,55) pixels. Further validation of our method is achieved by showing that our estimated landmark positions on patient images fall within the inter-observer variability in the ground truth. The effectiveness of our approach to analyse patient images is then established by calculating dense displacement fields throughout a cardiac cycle, and were found to be physiologically consistent. Circumferential strains were estimated at the apical, mid and basal slices of the heart, and were shown to compare favorably with those of HARP over the entire cardiac cycle, except in a few (∼4) of the segments in the 17-segment AHA model. The radial strains, however, are underestimated by our method in most segments when compared with HARP. CONCLUSIONS: In summary, we have demonstrated the capability of CIV to accurately and efficiently quantify cardiac deformation from tMR images. Furthermore, physiologically consistent displacement fields and circumferential strain curves in most regions of the heart indicate that our approach, upon automating some pre-processing steps and testing in clinical trials, can potentially be implemented in a clinical setting.

Effects of activation pattern and active stress development on myocardial shear in a model with adaptive myofiber reorientation.

It has been hypothesized that myofiber orientation adapts to achieve a preferred mechanical loading state in the myocardial tissue. Earlier studies tested this hypothesis in a combined model of left ventricular (LV) mechanics and remodeling of myofiber orientation in response to fiber cross-fiber shear, assuming synchronous timing of activation and uniaxial active stress development. Differences between computed and measured patterns of circumferential-radial shear strain E(cr) were assumed to be caused by limitations in either the LV mechanics model or the myofiber reorientation model. Therefore, we extended the LV mechanics model with a physiological transmural and longitudinal gradient in activation pattern and with triaxial active stress development. We investigated the effects on myofiber reorientation, LV function, and deformation. The effect on the developed pattern of the transverse fiber angle α(t,0) and the effect on global pump function were minor. Triaxial active stress development decreased amplitudes of E(cr) towards values within the experimental range and resulted in a similar base-to-apex gradient during ejection in model computed and measured E(cr). The physiological pattern of mechanical activation resulted in better agreement between computed and measured strain in myofiber direction, especially during isovolumic contraction phase and first half of ejection. In addition, remodeling was favorable for LV pump and myofiber function. In conclusion, the outcome of the combined model of LV mechanics and remodeling of myofiber orientation is found to become more physiologic by extending the mechanics model with triaxial active stress development and physiological activation pattern.

Left and right ventricular strain-volume/area loops: a narrative review of current physiological understanding and potential clinical value.

Traditionally, echocardiography is used for volumetric measurements to aid in assessment of cardiac function. Multiple echocardiographic-based assessment techniques have been developed, such as Doppler ultrasound and deformation imaging (e.g., peak global longitudinal strain (GLS)), which have shown to be clinically relevant. Volumetric changes across the cardiac cycle can be related to deformation, resulting in the Ventricular Strain-Volume/Area Loop. These Loops allow assessment of the dynamic relationship between longitudinal strain change and volumetric change across both systole and diastole. This integrated approach to both systolic and diastolic function assessment may offer additional information in conjunction with traditional, static, measures of cardiac function or structure. The aim of this review is to summarize our current understanding of the Ventricular Strain-Volume/Area Loop, describe how acute and chronic exposure to hemodynamic stimuli alter Loop characteristics, and, finally, to outline the potential clinical value of these Loops in patients with cardiovascular disease. In summary, several studies observed Loop changes in different hemodynamic loading conditions and various (patho)physiological conditions. The diagnostic and prognostic value, and physiological interpretation remain largely unclear and have been addressed only to a limited extent.

Novel Findings of Early Cardiac Dysfunction in Patients With Childhood-Onset Inflammatory Bowel Disease Using Layer-Specific Strain Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them. METHODS: A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn's disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants. RESULTS: Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P < .001) and CD (P < .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer. CONCLUSIONS: Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.

Patients with inflammatory bowel disease are at a higher risk of developing cardiovascular disease than healthy individuals. Our study revealed that children and young adults with childhood-onset inflammatory bowel disease already have reduced myocardial deformability.

Effects of enzyme replacement therapy on cardiac function in classic infantile Pompe disease.

OBJECTIVE: Patients with classic infantile Pompe disease are born with a hypertrophic cardiomyopathy, which resolves after treatment with Enzyme replacement therapy (ERT). We aimed to assess potential deterioration of cardiac function over time using myocardial deformation analysis. METHODS: Twenty-seven patients treated with ERT were included. Cardiac function was assessed at regular time intervals (before and after start with ERT) using conventional echocardiography and myocardial deformation analysis. Separate linear mixed effect models were used to asses temporal changes within the first year and the long-term follow-up period. Echocardiograms of 103 healthy children served as controls. RESULTS: A total of 192 echocardiograms were analyzed. Median follow-up was 9.9 years (IQR: 7.5-16.3). Mean LVMI before start of ERT was increased 292.3 g/m2 (95% CI: 202.8-381.8, mean Z-score + 7.6) and normalized after 1 year of ERT 87.3 g/m2 (CI: 67.5-107.1, mean Z-score + 0.8, p < 0.001). Mean shortening fraction was within normal limits before start of ERT, up to 22 years of follow-up. Cardiac function measured by RV/LV longitudinal, and circumferential strain was diminished before start of ERT, but normalized (<-16%) within 1 year after start of ERT, and all remained within normal limits during follow-up. Only LV circumferential strain gradually worsened in Pompe patients (+0.24%/year) during follow-up compared to controls. LV longitudinal strain was diminished in Pompe patients, but did not change significantly over time compared to controls. CONCLUSION: Cardiac function, measured using myocardial deformation analysis, normalizes after start of ERT, and seems to remain stable over a median follow-up period of 9.9 years.

Acute phase segmental radial strain correlates with recovery and late gadolinium extent in ST-elevation myocardial infarction (STEMI): analysis of the abciximab intracoronary versus intravenously drug application in STEMI substudy.

BACKGROUND: The role of regional strain evaluation in patients with acute reperfused ST-elevation myocardial infarction (STEMI) is not well determined. The objective of this study was the description of regional strain characteristics in the acute and chronic phase of myocardial infarction and its correlation with symptom-to-balloon time and final extent of myocardial scar assessed by cardiac magnetic resonance imaging. METHODS: The study cohort has been derived from the randomized controlled Abciximab Intracoronary versus Intravenously Drug Application in STEMI (AIDA STEMI) trial enrolled at the University of Ulm. All patients received comprehensive cardiac magnetic resonance imaging examinations in the acute phase and 6 months later. RESULTS: There was a significant improvement of all global deformation indices over time (global longitudinal strain: -13.1%±5.1% to -15.5%±5.8%, P=0.001; global circumferential strain: -14.4%±3.7% to -16.8%±3.6%, P<0.0001; global radial strain: 28.1%±8.7% to 31.9%±9.2%, P=0.0002). Mean radial strain of ischemic segments significantly improved (16.6%±10.8% to 23.7%±12.8%, P<0.0001), while mean radial strain of remote segments remained unchanged (40.2%±9.4% to 39.4%±9.4%, P=0.570). There was a significant correlation between acute phase radial strain of ischemic segments and either symptom-to-balloon time (P=0.013), as well as extent of late gadolinium enhancement at follow-up (P<0.0001). Using a cut-off of ≤27%, acute phase radial strain predicted infarction of the corresponding segment with high sensitivity and specificity (74.4% and 69.0% respectively, P<0.001). CONCLUSIONS: Segmental radial strain in the acute phase of infarction showed a significant correlation to either symptom-to-balloon-time and the extent of late gadolinium enhancement at follow-up, thus potentially serving as early surrogate for left ventricular remodeling and outcome in STEMI.

Changes in Left Ventricular Mechanics After Sleeve Gastrectomy.

OBJECTIVE: The aim of this study was to examine echocardiographic parameters of left ventricle (LV) mechanics in obese patients before and after sleeve gastrectomy (SG). DESIGN AND METHODS: Twenty-five obese individuals submitted to laparoscopic SG were enrolled in this study. Echocardiography was performed before and after the procedure, and left ventricle mechanics were evaluated by speckle tracking imaging. RESULTS: Before surgery, altered global longitudinal strain (GLS) values were present in 56% of the patients. In a mean follow-up of 3.6 ± 0.5 months after surgery, there was an increase in GLS values (from 17.4 ± 3.2 to 19.3 ± 2.7%, P = 0.01). There was an inverse correlation between the absolute values of GLS in the preoperative period and the variation in the GLS at follow-up (r = 0.577, P = 0.002). Measurements of global circumferential strain (GCS), global radial strain (GRS), and LV twist were normal preoperatively and did not change after surgery. CONCLUSIONS: Altered global longitudinal strain values were common in young obese patients. Sleeve gastrectomy increased global longitudinal strain even in the early postoperative phase without promoting changes in global radial strain, global circumferential strain, and left ventricle twist measurements.

The combined effects of cardiac geometry, microcirculation, and tissue characteristics on cardiac systolic and diastolic function in subclinical diabetes mellitus-related cardiomyopathy.

BACKGROUND: Diabetes mellitus-related cardiomyopathy has recently been described as a distinct progression of left ventricular (LV) systolic and diastolic dysfunction. Pathological changes in the myocardium may explain the development of two different phenotypes. We evaluated the effects of LV geometry, myocardial microcirculation, and tissue characteristics on cardiac deformation in patients with subclinical type 2 diabetes mellitus (T2DM) utilizing multiparametric cardiac magnetic resonance (CMR) imaging. METHODS: A total of 135 T2DM patients and 55 matched controls were prospectively enrolled and performed multiparametric CMR examination. CMR-derived parameters including cardiac geometry, function, microvascular perfusion, T1 mapping, T2 mapping, and strain were analyzed and compared between T2DM patients and controls. RESULTS: The univariable and multivariable analysis of systolic and diastolic function revealed that longer duration of diabetes was associated with decreased longitudinal peak systolic strain rate (PSSR-L) (ß = 0.195, p = .013), and higher remodeling index and higher extracellular volume (ECV) tended to correlate with decreased longitudinal peak diastolic strain rate (PDSR-L) (remodeling index, ß = -0.339, p = .000; ECV, ß = -0.172, p = .026), whereas microvascular perfusion index and T2 value affected both PSSR-L (perfusion index, ß = -0.328, p = .000; T2 value, ß = 0.306, p = .000) and PDSR-L (perfusion index, ß = 0.209, p = .004; T2 value, ß = -0.275, p = .000) simultaneously. CONCLUSIONS: The LV concentric remodeling and myocardial fibrosis correlated with diastolic function, and perfusion function and myocardial edema were associated with both LV systolic and diastolic function.

Microstructurally Anchored Cardiac Kinematics by Combining In Vivo DENSE MRI and cDTI.

Metrics of regional myocardial function can detect the onset of cardiovascular disease, evaluate the response to therapy, and provide mechanistic insight into cardiac dysfunction. Knowledge of local myocardial microstructure is necessary to distinguish between isotropic and anisotropic contributions of local deformation and to quantify myofiber kinematics, a microstructurally anchored measure of cardiac function. Using a computational model we combine in vivo cardiac displacement and diffusion tensor data to evaluate pointwise the deformation gradient tensor and isotropic and anisotropic deformation invariants. In discussing the imaging methods and the model construction, we identify potential improvements to increase measurement accuracy. We conclude by demonstrating the applicability of our method to compute myofiber strain in five healthy volunteers.

Progression of Right Ventricular Systolic Dysfunction Detected by Myocardial Deformation Imaging in Asymptomatic Preterm Children.

BACKGROUND: To detect progression of right ventricular (RV) systolic dysfunction (RVSD) in asymptomatic preterm children from infancy to 24-month corrected age, using velocity vector imaging (VVI). METHODS: Retrospective study comparing sequential RV longitudinal peak systolic strain (LPSS) from 24 children born at < 33 weeks of gestational age and 10 term infants recruited as controls, obtained at a mean of 4-month (first exam) and 24-month corrected age (second exam). RESULTS: In 7/24 (29.2%) of preterm children, RV LPSS of < 16%, defined as RVSD, was detected at the second exam; 5/7 of these children had RV LPSS > 16% at the first exam, and only 2/7 of these children had a history of moderate or severe bronchopulmonary dysplasia. CONCLUSION: In asymptomatic preterm children, routine echocardiographic screening using VVI could detect RVSD which could progress from 4-24 month corrected age.

Comparison of two-dimensional strain analysis using vendor-independent and vendor-specific software in adult and pediatric patients.

INTRODUCTION: Two-dimensional strain analysis is a powerful analysis modality, however, clinical utilization has been limited by variability between different analysis systems and operators. We compared strain in adults and children using vendor-specific and vendor-independent software to evaluate variability. METHODS: One hundred and ten subjects (50/110 pediatric, 80/110 normal left ventricular function) had echocardiograms with a General Electric ultrasound scanner between September 2010 and January 2012. Left ventricular longitudinal strain was derived with EchoPAC (General Electric, v10.8.1), a vendor-specific software, and Velocity Vector Imaging (Siemens, v3.5), which is vendor-independent. Three independent readers analyzed all the echocardiograms yielding 330 datasets. RESULTS: Mean left ventricular global longitudinal Lagrangian strain was -18.1 ± SD 4.4% for EchoPAC and -15.3 ± SD 4.1% for Velocity Vector Imaging. Velocity Vector Imaging yielded lower absolute global longitudinal Lagrangian strain by mean 2.9 (±SD 2.7, p < 0.0001), and lower regional longitudinal strain. These differences persisted in normal subjects versus those with cardiomyopathy. Longitudinal strain differences were slightly higher in the pediatric cohort. There was no significant difference in inter-observer longitudinal strain and a small difference in intra-observer strain between analysis systems. On repeat measurements, a significant change in global longitudinal Lagrangian strain occurred after the difference exceeded 3-5 strain points for EchoPAC and Velocity Vector Imaging, respectively. CONCLUSION: Velocity Vector Imaging produces lower left ventricular longitudinal strain values versus EchoPAC for the same echo images. Both systems have similar inter-observer variability, Velocity Vector Imaging slightly higher intra-observer variability. A statistically significant change in global longitudinal Lagrangian strain occurs with changes >3-5 strain points on repeat measurements. Strain values between the systems are not interchangeable.