Properties Of Myocardial Tissue Research Articles

Abstract 4139162: Optical coherence tomography measures mechanical contractile properties of the beating murine heart

Introduction: Optical imaging techniques can characterize properties of tissue at high temporal and spatial resolution, offering unique insights into electrically excitable tissues such as nerve and muscle. We hypothesized that the gated high-speed optical coherence tomography (OCT) could profile the contractile properties of mouse myocardial tissue and facilitate investigations of microscale mechanical function in the beating heart. Methods: C57BL/6 male mice (n=6) underwent a sternotomy while anesthetized and ventilated and were imaged at baseline with OCT. Another cohort of C57BL/6 male mice (n=6) were sacrificed and the hearts were ex vivo perfused with crystalloid using a Langendorff system. These hearts were imaged at baseline and after inhibition of contractile function with blebbistatin. OCT was performed using a custom tissue stabilizer and a Thorlabs TEL 321 OCT system, which was synchronized to physiologic signals using custom hardware and software and cardiac pacing protocols (Fig. 1A and 1B). OCT cross-sectional B-scan images (Fig. 1C) were obtained throughout multiple cardiac cycles in both in vivo and ex vivo preparations. Data were processed in MATLAB and ImageJ using the workflow in Fig. 1D. Results: Highly reproducible cross-sectional mean intensity changes were observed over the contractile cycle in vivo and ex vivo (Fig. 1E, left and middle). With mechanical contraction inhibited by blebbistatin, this cyclical intensity extinguished, linking the optical scattering change measured by OCT to myocardial contraction (Fig. 1E, right). B-scan curves averaged over multiple mice and temporally aligned with the ECG waveform (Fig. 1F) demonstrate a signal intensity waveform that reproducibly varies with the contractile cycle for both in vivo and ex vivo preparations. In vivo and ex vivo baseline waveforms both had peak intensity during systole and minimum in end-diastole (Fig. 1F). Reproducibility in ex vivo beating heart preparations without blood perfusion provides evidence that myocardial mechanical properties, not red blood cell flow, generate the intensity changes. Conclusion: Gated high-speed OCT imaging can quantify the mechanical contraction wave in the myocardium. Combined with gated OCT angiography, OCT techniques will provide high resolution imaging of both blood flow and mechanical contractility of the beating heart in small animal models of heart disease.

Mechanical wave velocities in acute myocardial infarction: an exploratory study using three-dimensional high frame rate echocardiography

Abstract Background Evaluation of cardiac function is crucial for management of patients with acute myocardial infarction (AMI). Recently, high frame rate (HFR) echocardiography has enabled identification of fast-propagating mechanical waves (MW) within the myocardium. These waves have the potential to offer unique insights into myocardial tissue properties, including edema and fibrosis. However, the potential of 3D HFR echocardiography to accurately quantify MW velocities and thereby assess myocardial stiffness in AMI patients remains unexplored. Purpose To assess the feasibility of a novel method for estimating MW velocities using 3D HFR echocardiography in patients with AMI compared to healthy controls. Methods Twenty patients with first time ST-elevation myocardial infarction were included within 48 hours after reperfusion therapy. We used a commercially available ultrasound scanner to acquire conventional 3D high-quality (~20 frames per second) acquisitions and subsequent 3D HFR recordings (~820 frames per second). The high-quality recording was used to extract a myocardial mask to define the region of interest in the HFR acquisition to detect the atrial kick wave and generate a comprehensive 3D map of MW propagation and velocities. We compared MW velocities between these patients and twenty age- and sex-matched healthy controls. Results MW velocities were successfully measured in 93% of participants (17 patients and 20 controls). Global MW velocities were significantly higher in AMI patients compared to healthy controls (2.1±0.6m/s vs. 1.5±0.2m/s, p<0.001). Territorial values, corresponding to the theoretical perfusion area of the three main coronary arteries, were significantly higher in infarct-related territories in patients when compared to same territories in controls for all coronary territories: Right coronary artery: 1.9±0.7 m/s vs. 1.4±0.3m/s, p<0.05; Circumflex artery: 3.1±1.5m/s vs. 1.7±0.4m/s, p<0.01; and Left anterior descending artery: 1.8±0.5m/s vs. 1.4±0.2m/s, p<0.01. Conclusions Estimation of MW velocities using a novel 3D HFR echocardiography method was feasible in most patients with AMI and all healthy controls. MW velocities were higher in patients compared to healthy controls and infarcted compared to non-infarcted coronary territories. These findings confirm the potential of non-invasive myocardial tissue characterization by MW imaging.Boxplot of MW velocities3D HFR MW visualisation

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.

Review of Myocardial Ischemia, Scar, and Viability Estimation with Molecular Magnetic Resonance Imaging.

Cardiovascular diseases, particularly myocardial ischemia from coronary artery obstruction, remain a leading cause of global morbidity. This review explores cardiac molecular magnetic resonance imaging (mMRI) and other molecular imaging techniques for the evaluation of myocardial ischemia, scarring, and viability. mMRI imaging methods provide detailed information on myocardial ischemia, edema, and scar tissue using techniques like cine imaging, T1 and T2 mapping, and gadolinium-based contrast agents. These methods enable the precise assessment of the myocardial tissue properties, crucial in diagnosing and treating cardiovascular diseases. Advanced techniques, such as the T1ρ and RAFFn methods, might provide enhanced contrast and sensitivity for the detection of myocardial scarring without contrast agents. Molecular probes, including gadolinium-based and protein-targeted contrast agents, improve the detection of molecular changes, facilitating early diagnosis and personalized treatment. Integrating MRI with positron emission tomography (PET) combines the high spatial and temporal resolution with molecular and functional imaging. Recent advancements in mMRI and molecular imaging have changed the evaluation of myocardial ischemia, scarring, and viability. Despite significant progress, extensive research is needed to validate these techniques clinically and further develop imaging methods for better diagnostic and prognostic outcomes.

Toward Enabling Cardiac Digital Twins of Myocardial Infarction Using Deep Computational Models for Inverse Inference.

Cardiac digital twins (CDTs) have the potential to offer individualized evaluation of cardiac function in a non-invasive manner, making them a promising approach for personalized diagnosis and treatment planning of myocardial infarction (MI). The inference of accurate myocardial tissue properties is crucial in creating a reliable CDT of MI. In this work, we investigate the feasibility of inferring myocardial tissue properties from the electrocardiogram (ECG) within a CDT platform. The platform integrates multi-modal data, such as cardiac MRI and ECG, to enhance the accuracy and reliability of the inferred tissue properties. We perform a sensitivity analysis based on computer simulations, systematically exploring the effects of infarct location, size, degree of transmurality, and electrical activity alteration on the simulated QRS complex of ECG, to establish the limits of the approach. We subsequently present a novel deep computational model, comprising a dual-branch variational autoencoder and an inference model, to infer infarct location and distribution from the simulated QRS. The proposed model achieves mean Dice scores of 0.457 ±0.317 and 0.302 ±0.273 for the inference of left ventricle scars and border zone, respectively. The sensitivity analysis enhances our understanding of the complex relationship between infarct characteristics and electrophysiological features. The in silico experimental results show that the model can effectively capture the relationship for the inverse inference, with promising potential for clinical application in the future. The code is available at https://github.com/lileitech/MI_inverse_inference.

Cardiac MRI T2 mapping with heart phase acquisition and improved motion-sensitized driven equilibrium blood suppression

Abstract Background Cardiovascular magnetic resonance (CMR) imaging relies on T2 mapping to assess myocardial tissue properties. However, T2 maps are subject to motion artifacts and signal interference, prompting exploration of techniques such as gradient-spin-echo (GraSE) sequences, heart phase acquisition, and dark blood (DB) imaging to improve image quality and reliability. Purpose This prospective study evaluates the T2 relaxation time (T2) variability and the image quality of T2 maps obtained in end-systole and end-diastole with and without fat saturation (FS), using GraSE sequence in CMR imaging. Furthermore, improved motion-sensitized driven-equilibrium (iMSDE) was compared with double inversion recovery (DIR) as an alternative DB technique. Materials and Methods Five variants of the DB GraSE sequence were developed and performed on a 1.5 Tesla MRI scanner. Forty-four healthy volunteers prospectively underwent the following sequences: GraSE in end-diastole (GraSE-ED), GraSE-ED with FS (GraSE-ED-FS), GraSE in end-systole (GraSE-ES), GraSE-ES with FS (GraSE-ES-FS), and commercial GraSE-ED (GraSE-CO). Four GraSE variants utilized iMSDE technique, while GraSE-CO used DIR for blood suppression. T2, image quality, and visual artifacts were measured. Results Ten volunteers were excluded due to image artifacts or missing datasets. Among the remaining 34 participants, the mean global T2 was measured. No significant differences were seen among all variants (P &amp;gt; .05 for all comparisons). Intra- and inter-reader agreement of global T2 values for all GraSE sequence were very good (r &amp;gt; 0.8 for both). Image quality was rated moderate or good for all variants of GraSE sequences. A lower incidence of artifacts was observed in end-systolic compared to end-diastolic imaging. Conclusion All variants of GraSE sequence are highly reproducible and myocardial T2 values did not significantly differ with heart phase. iMSDE is feasible as an alternative DB technique for T2 mapping enabling acquisition in systole, which shows a lower incidence of artifacts compared to diastole.

The Significance of Parametric Mapping in Advanced Cardiac Imaging.

Cardiac magnetic resonance imaging has witnessed a transformative shift with the integration of parametric mapping techniques, such as T1 and T2 mapping and extracellular volume fraction. These techniques play a crucial role in advancing our understanding of cardiac function and structure, providing unique insights into myocardial tissue properties. Native T1 mapping is particularly valuable, correlating with histopathological fibrosis and serving as a marker for various cardiac pathologies. Extracellular volume fraction, an early indicator of myocardial remodeling, predicts adverse outcomes in heart failure. Elevated T2 relaxation time in cardiac MRI indicates myocardial edema, enabling noninvasive and early detection in conditions like myocarditis. These techniques offer precise insights into myocardial properties, enhancing the accuracy of diagnosis and prognosis across a spectrum of cardiac conditions, including myocardial infarction, autoimmune diseases, myocarditis, and sarcoidosis. Emphasizing the significance of these techniques in myocardial tissue analysis, the review provides a comprehensive overview of their applications and contributions to our understanding of cardiac diseases.

CMR Mapping: The 4th-Era Revolution in Cardiac Imaging.

Cardiac magnetic resonance (CMR) imaging has witnessed substantial progress with the advent of parametric mapping techniques, most notably T1 and T2 mapping. These advanced techniques provide valuable insights into a wide range of cardiac conditions, including ischemic heart disease, cardiomyopathies, inflammatory cardiomyopathies, heart valve disease, and athlete's heart. Mapping could be the first sign of myocardial injury and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. The ability of parametric mapping to offer a quantitative assessment of myocardial tissue properties addresses the limitations of conventional CMR methods, which often rely on qualitative or semiquantitative data. However, challenges persist, especially in terms of standardization and reference value establishment, hindering the wider clinical adoption of parametric mapping. Future developments should prioritize the standardization of techniques to enhance their clinical applicability, ultimately optimizing patient care pathways and outcomes. In this review, we endeavor to provide insights into the potential contributions of CMR mapping techniques in enhancing the diagnostic processes across a range of cardiac conditions.

Native myocardial T1 mapping: influence of spatial resolution on quantitative results and reproducibility.

Myocardial mapping techniques can be used to quantitatively assess alterations in myocardial tissue properties. This study aims to evaluate the influence of spatial resolution on quantitative results and reproducibility of native myocardial T1 mapping in cardiac magnetic resonance imaging (MRI). In this cross-sectional study with prospective data collection between October 2019 and February 2020, 50 healthy adults underwent two identical cardiac MRI examinations in the radiology department on the same day. T1 mapping was performed using a MOLLI 5(3)3 sequence with higher (1.4 mm × 1.4 mm) and lower (1.9 mm × 1.9 mm) in-plane spatial resolution. Global quantitative results of T1 mapping were compared between high-resolution and low-resolution acquisitions using paired t-test. Intra-class correlation coefficient (ICC) and Bland-Altman statistics (absolute and percentage differences as means ± SD) were used for assessing test-retest reproducibility. There was no significant difference between global quantitative results acquired with high vs. low-resolution T1 mapping. The reproducibility of global T1 values was good for high-resolution (ICC: 0.88) and excellent for low-resolution T1 mapping (ICC: 0.95, P=0.003). In subgroup analyses, inferior test-retest reproducibility was observed for high spatial resolution in women compared to low spatial resolution (ICC: 0.71 vs. 0.91, P=0.001) and heart rates >77 bpm (ICC: 0.53 vs. 0.88, P=0.004). Apical segments had higher T1 values and variability compared to other segments. Regional T1 values for basal (ICC: 0.81 vs. 0.89, P=0.023) and apical slices (ICC: 0.86 vs. 0.92, P=0.024) showed significantly higher reproducibility in low-resolution compared to high-resolution acquisitions but without differences for midventricular slice (ICC: 0.91 vs. 0.92, P=0.402). Based on our data, we recommend a spatial resolution on the order of 1.9 mm × 1.9 mm for native myocardial T1 mapping using a MOLLI 5(3)3 sequence at 1.5 T particularly in individuals with higher heart rates and women.

Enhanced Extraction of Activation Time and Contractility From Myocardial Strain Data Using Parameter Space Features and Computational Simulations.

A computational model enables the extraction of two critical myocardial tissue properties: activation time (AT) and contractility (Con) from recorded cardiac strains. However, interference between these parameters reduces the precision and accuracy of the extraction process. This study investigates whether leveraging features in the parameter space can enhance parameter extraction. We utilized a computational model to simulate sarcomere mechanics, creating a parameter space grid of 41 × 41 AT and Con pairs. Each pair generated a simulated strain pattern, and by scanning the grid, we identified cohorts of similar strain patterns for each simulation. These cohorts were represented as binary images-synthetic fingerprints-where the position and shape of each blob indicated extraction uniqueness. We also generated a measurement fingerprint for a strain pattern from a patient with left bundle branch block and compared it to the synthetic fingerprints to calculate a proximity map based on their similarity. This approach allowed us to extract AT and Con using both the measurement fingerprint and the proximity map, corresponding to simple optimization and enhanced parameter extraction methods, respectively. Each synthetic fingerprint consisted of a single connected blob whose size and shape varied characteristically within the parameter space. The AT values extracted from the measurement fingerprint and the proximity map ranged from -59 to 19 ms and from -16 to 14 ms, respectively, while Con values ranged from 48% to 110% and from 85% to 110%, respectively. This study demonstrates that similarity in simulations leads to an asymmetric distribution of parameter values in the parameter space. By using a proximity map, this distortion is considered, significantly improving the accuracy of parameter extraction.

Diagnosis and management of patients with left ventricular hypertrophy: Role of multimodality cardiac imaging. A scientific statement of the Heart Failure Association of the European Society of Cardiology.

Left ventricular (LV) hypertrophy consists in an increased LV wall thickness. LV hypertrophy can be either secondary, in response to pressure or volume overload, or primary, i.e. not explained solely by abnormal loading conditions. Primary LV hypertrophy may be due to gene mutations or to the deposition or storage of abnormal substances in the extracellular spaces or within the cardiomyocytes (more appropriately defined as pseudohypertrophy). LV hypertrophy is often a precursor to subsequent development of heart failure. Cardiovascular imaging plays a key role in the assessment of LV hypertrophy. Echocardiography, the first-line imaging technique, allows a comprehensive assessment of LV systolic and diastolic function. Cardiovascular magnetic resonance provides added value as it measures accurately LV and right ventricular volumes and mass and characterizes myocardial tissue properties, which may provide important clues to the final diagnosis. Additionally, scintigraphy with bone tracers is included in the diagnostic algorithm of cardiac amyloidosis. Once the diagnosis is established, imaging findings may help predict future disease evolution and inform therapy and follow-up. This consensus document by the Heart Failure Association of the European Society of Cardiology provides an overview of the role of different cardiac imaging techniques for the differential diagnosis and management of patients with LV hypertrophy.

Integrated bioinformatics and machine learning algorithms reveal the critical cellular senescence-associated genes and immune infiltration in heart failure due to ischemic cardiomyopathy.

Heart failure (HF) is the final stage of many cardiovascular illnesses and the leading cause of death worldwide. At the same time, ischemic cardiomyopathy has replaced valvular heart disease and hypertension as the primary causes of heart failure. Cellular senescence in heart failure is currently receiving more attention. In this paper, we investigated the correlation between the immunological properties of myocardial tissue and the pathological mechanisms of cellular senescence during ischemic cardiomyopathy leading to heart failure (ICM-HF) using bioinformatics and machine learning methodologies. Our goals were to clarify the pathogenic causes of heart failure and find new treatment options. First, after obtaining GSE5406 from the Gene Expression Omnibus (GEO) database and doing limma analysis, differential genes (DEGs) among the ICM-HF and control groups were identified. We intersected these differential genes with cellular senescence-associated genes (CSAG) via the CellAge database to obtain 39 cellular senescence-associated DEGs (CSA-DEGs). Then, a functional enrichment analysis was performed to elucidate the precise biological processes by which the hub genes control cellular senescence and immunological pathways. Then, the respective key genes were identified by Random Forest (RF) method, LASSO (Least Absolute Shrinkage and Selection Operator) algorithms, and Cytoscape's MCODE plug-in. Three sets of key genes were taken to intersect to obtain three CSA-signature genes (including MYC, MAP2K1, and STAT3), and these three CSA-signature genes were validated in the test gene set (GSE57345), and Nomogram analysis was done. In addition, we assessed the relationship between these three CSA- signature genes and the immunological landscape of heart failure encompassing immunological infiltration expression profiles. This work implies that cellular senescence may have a crucial role in the pathogenesis of ICM-HF, which may be closely tied to its effect on the immune microenvironment. Exploring the molecular underpinnings of cellular senescence during ICM-HF is anticipated to yield significant advances in the disease's diagnosis and therapy.

Magnetic resonance imaging reference values for cardiac morphology, function and tissue composition in adolescents.

Cardiovascular magnetic resonance (CMR) is a precise tool for the assessment of cardiac anatomy, function, and tissue composition. However, studies providing CMR reference values in adolescence are scarce. We aim to provide sex-specific CMR reference values for biventricular and atrial dimensions and function and myocardial relaxation times in this population. Adolescents aged 15-18 years with no known cardiovascular disease underwent a non-contrast 3-T CMR scan between March 2021 and October 2021. The imaging protocol included a cine steady-state free-precession sequence for the analysis of chamber size and function, as well as T2-GraSE and native MOLLI T1-mapping for the characterization of myocardial tissue. CMR scans were performed in 123 adolescents (mean age 16±0.5 years, 52% girls). Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.7±11.6 vs 78.1±8.3ml/m2, p<0.001; and 101.3±14.1 vs 84.1±10.5ml/m2, p<0.001), as was the indexed left ventricular mass (48.5±9.6 vs 36.6±6.0g/m2, p<0.001). Left ventricular ejection fraction showed no significant difference by sex (62.2±4.1 vs 62.8±4.2%, p=0.412), whereas right ventricular ejection fraction trended slightly lower in boys (55.4±4.7 vs. 56.8±4.4%, p=0.085). Indexed atrial size and function parameters did not differ significantly between sexes. Global myocardial native T1 relaxation time was lower in boys than in girls (1215±23 vs 1252±28ms, p<0.001), whereas global myocardial T2 relaxation time did not differ by sex (44.4±2.0 vs 44.1±2.4ms, p=0.384). Sex-stratified comprehensive percentile tables are provided for most relevant cardiac parameters. This cross-sectional study provides overall and sex-stratified CMR reference values for cardiac dimensions and function, and myocardial tissue properties, in adolescents. This information is useful for clinical practice and may help in the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in this population. Instituto de Salud Carlos III (PI19/01704).

Association between Myocardial Iron Overload and Diffuse Myocardial Fibrosis in Thalassemia Major

Cardiovascular magnetic resonance (CMR) is the gold standard for the non-invasive assessment of myocardial tissue properties. All CMR relaxation times (T1, T2 and T2*) are reduced in presence of iron deposits. In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with thalassemia major (TM). Myocardial extracellular volume( ECV) by CMR has been introduced as a good surrogate imaging marker of diffuse myocardial fibrosis. This the first study to evaluate the association between ECV values and all three relaxation times in TM. 108 β-TM patients (62 females, 40.16±8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, underwent CMR. T2*, T2, and native and post-contrast T1 values were assessed in all 16 myocardial segments. Segmental ECV values were calculated with input of native and post-contrast myocardial segmental and blood pool T1 values and same-day hematocrit. Global value was the mean of all segmental values. Significant MIO (global heart T2*<20ms) was found in 9 (8.3%) patients. Global ECV values were significantly higher in patients with significant MIO than in patients without significant MIO (40.07±10.62% vs. 31.85±5.71%; p=0.049) (Figure 1A). T2 images were acquired in 90 patients, of whom 40 (44.4%) had a normal global heart T2 value, 9 (8.3%) a reduced global heart T2 value, and 41 (45.6%) an increased global heart T2 value. Patients with reduced global heart T2 value showed significantly higher global ECV values than patients with normal (40.25±9.74% vs 30.54±5.49%; p<0.0001) as well as increased (40.25±9.74% vs 32.63±5.37%; p=0.002) global heart T2 value (Figure 1B). Global heart T1 values were normal in 54 (50%) patients, reduced in 50 (46.3%) patients and increased in 4 (3.7%) patients. Global ECV values tended to be higher among patients with increased T1 value (37.13±4.46%) versus both patients with normal or reduced T1 value (31.84±6.52% and 32.93±6.7%, respectively), but the difference among the three groups was not significant (p=0.259) (Figure 1C). The finding about the increased myocardial ECV in TM patients with reduced global heart T2* value seems to suggest that in TM MIO plays a crucial pathophysiological role in the development of diffuse myocardial fibrosis. This hypothesis is supported by the fact that patients with reduced global heart T2 value showed significantly higher global ECV values than patients with normal or increased global heart T2 value. As TM patients can develop chronic inflammation, the increased myocardial T2 value can be due to myocardial inflammation, that counterbalances the iron effects in non-heavily iron-overloaded hearts. Although myocardial inflammation can affect ECV, confounding the correlation between ECV and fibrosis, the absence of a difference in ECV values between patients with normal and increased global heart T2 value seems to suggest the dominance of fibrosis over inflammation. The absence of a link between decreased T1 and increased ECV may be explained by the fact that although in borderline patients T1 mapping has an higher sensitivity for MIO detection in comparison to the T2* technique, T1 values are not specific for iron and show prolongation in presence of diffuse myocardial fibrosis. Longitudinal prospective studies are needed to clarify the temporal association between myocardial iron overload and diffuse fibrosis and to obtain a better understanding of the implications of the presence of diffuse myocardial fibrosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 11841: Activation of Cardiac Fibulin-4 Protects Against Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Cutis laxa is a rare disorder caused by mutations in the extracellular matrix (ECM) protein Fibulin-4 and patients are susceptible to stress-induced cardiac dysfunction. Mice with a 75% reduction in Fibulin-4 expression (Fibulin-4 R/R ) developed cardiac hypertrophy, dilation and dysfunction as well as aortic aneurysms. The prevailing view is that this is the result of aortic and/or valvular disease, given that Fibulin-4 is believed to be exclusively involved in arterial and valvular elastogenesis and collagen deposition. Yet mortality after cardiac pressure-overload through transverse aortic constriction (TAC) was also increased in haploinsufficient Fibulin-4 +/R mice with a 50% reduced Fibulin-4 expression compared to wildtype animals. To determine whether the TAC-induced dilated cardiomyopathy in haploinsufficient Fibulin-4 +/R mice is a primary manifestation resulting from ECM abnormalities we analyzed the hearts of these mice for the presence of Fibulin-4 expression. Fibulin-4 expression was found to be activated throughout the entire myocardium in TAC-exposed wildtype animals. TAC-exposed Fibulin-4 +/R animals did not show this strong increase in myocardial Fibulin-4 expression but displayed emergence of altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including decreased focal adhesion kinase activity similar to TAC-exposed wildtype animals. Moreover, reduced Fibulin-4 expression aggravated TAC-induced cardiac fibrosis and pulmonary congestion. In microtissues derived from neonatal Fibulin-4 deficient hearts, Fibulin-4 deficiency decreased the beating frequency and contractile force of microtissues. It also reduced the maximal force-generating capacity of single membrane-permeabilized cardiomyocytes. Our findings demonstrate novel functions for Fibulin-4 in cardiac homeostasis, and show that reduced Fibulin-4 expression drives myocardial disease in response to cardiac pressure overload independent of aortic valvular pathology. These so far unrecognized effects of Fibulin-4 on myocardial function could have important implications both for patients with connective tissue disorders and for the general population in response to pressure overload.

Cardiac magnetic resonance imaging derived reference values for ventricular anatomy and function and myocardial tissue characterization in adolescents: the EnIGMA study

Abstract Introduction Cardiac magnetic resonance (CMR) imaging is a precise tool for the assessment of cardiac anatomy and function. However, studies providing reference values for CMR parameters, including myocardial tissue properties, in healthy adolescents are scarce. Purpose To provide CMR derived reference values for biventricular mass, volumes and function measured by cine steady-state free-precession (SSFP) sequences and myocardial tissue relaxation properties as measured by native T1- and T2-mapping sequences in healthy adolescents. Methods A comprehensive non-contrast CMR study was performed in healthy adolescents aged 15 to 18 years enrolled in the “Early ImaginG Markers of unhealthy lifestyles in Adolescents” (EnIGMA) project using a 3-Tesla CMR scanner between March 2021 and October 2021. The imaging protocol included a cine SSFP to provide high-quality images for chamber size and function analysis, and a T2-GraSE mapping and native T1-mapping sequences (MOLLI Scheme 5 (3) 3) to provide precise myocardial relaxation time properties. Images were analyzed by experienced observers using the Cardiac Analysis tool available at IntelliSpace Portal following a standard protocol. In cine SSFP sequences, right and left ventricles were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation, respectively (Figure 1A, B). Native T1 and T2 maps were analyzed in a mid-ventricular short axis slice and summarized values per individual were determined (Figure 1C, D). Student's t-tests were used for between-gender comparisons. Results CMR scans were performed in 123 adolescents (63 girls, 51.2%) with a mean age of 16.0 years (standard deviation (SD)=0.5), mean body mass index of 21.4 (SD=3.2) kg/m2, mean body surface area of 1.69 (SD=0.16) m2, and mean heart rate during CMR acquisitions of 69 (SD=11) beats/minute. Reference percentiles (P) 3, 10, 25, 50, 75, 90 and 97 for the different parameters analyzed by gender are provided in Figure 2. Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.5 vs 78.1 ml/m2, p&amp;lt;0.01; and 101.1 vs 84.2 ml/m2, p&amp;lt;0.01), as well as the indexed cardiac mass (48.4 vs 36.4 g/m2, p&amp;lt;0.01). Left ventricular ejection fraction (LVEF) was similar in boys and girls (62.0 vs. 62.9%, p=0.23), whereas right ventricular ejection fraction was slightly lower in boys than in girls (55.3 vs. 57.1%, p=0.03). Mean myocardial native T1 relaxation time was 1253 (SD=28) ms in girls and 1215 (SD=23) ms in boys (p&amp;lt;0.01), whereas mean myocardial T2 relaxation time was 44.1 (SD=2.3) ms and 44.4 (SD=2.0) ms in girls and boys, respectively (p=0.46). Conclusion This study provided CMR derived reference values for biventricular anatomy, function, and myocardial tissue properties, in healthy adolescents aged 15 to 18 years. This information may be useful for the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in adolescent population. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III (ISCIII)-Fondo de Investigaciόn SanitariaEuropean Regional Development Fund/European Social Fund (“A way to make Europe”/“Investing in your future”)

Epicardial adipose tissue of atrioventricular grooves is a reliable and early MRI biomarker of the effect of metabolic diseases on atrial myocardium

Abstract Introduction Epicardial adipose tissue (EAT), the visceral adipose tissue surrounding the heart, is implicated in a host of cardiovascular diseases playing a transducer role between systemic metabolic conditions and the myocardium, as illustrated by higher risk of atrial fibrillation in patients with diabetes or obesity. MRI affords comprehensive and non-invasive insights into myocardial structure, function and tissue properties. However, the clinical usefulness of whole atrial EAT is limited by its challenging measurability in clinical routine in several imaging modalities, including MRI. Purpose We hypothesized that atrioventricular groove epicardial adipose tissue (GEAT) which can be measured routinely based on established anatomic landmarks may be: 1) a relevant surrogate of atrial EAT and 2) a relevant imaging biomarker to characterize atrial alterations in patients with varied degrees of metabolic disorders. Methods Ninety-nine patients from the METACARDIS cohort (EU FP7) who had MRI, all in sinus rhythm and without overt clinical heart disease, were divided into 4 groups based on distinct metabolic profiles: metabolic syndrome (MS, n=24), severe obesity (SO, BMI ≥35 kg/m2, n=17), type-2 diabetes (T2D, n=41) and healthy controls (n=17). Atrioventricular groove EAT volume was measured from cine SSFP MRI images in four-, three-, two-chamber and short-axis views; atrial EAT volume was measured from four- and two-chamber views. Native T1-mapping values of EAT at the anterior atrioventricular groove excluding the coronary vessels were measured from the MOLLI sequence (basal short-axis slice). Results We found a high correlation between GEAT and atrial EAT volumes (r=0.96; p&amp;lt;0.0001) indicating that GEAT may reflect global atrial EAT volume. Next, we compared GEAT volume across study groups and found an increased GEAT volume in the 3 groups of patients with metabolic diseases compared to controls, with a significantly higher volume in MS (4.7±1.5 ml), SO (4.1±1.2 ml), and T2D (3.7±1.1 ml) than in Controls (2.6±0.6 ml; p≤0.001, p≤0.01, p≤0.05, respectively). In addition, T2D patients had lower native T1 values within GEAT compared to healthy controls (250±26 ms versus 280±31 ms; p≤0.01). Conclusion Atrioventricular groove EAT can be easily measured from conventional cine SSFP MRI images and could be used as a surrogate of global atrial EAT. Both volume and properties of GEAT are related to the metabolic status of patients. Furthermore, given its pure epicardial origin and pericoronary distribution, GEAT appears as a relevant biomarker of metabolic impacts on atrial myocardium. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Annee-recherche, Agence Regionale de Sante Ile-de-France

Predictors of shear wave propagation speed assessed by shear wave elastography

Abstract Background Cardiac shear wave elastography (SWE) is a novel ultrasound-based method that assesses the propagation speed of shear waves travelling in the myocardium induced by e.g. mitral valve closure (MVC). The propagation speed of these waves is related to the stiffness of the myocardium. The capability of SWE to evaluate myocardial stiffness has already been demonstrated in several publications. However, which factors beside the intrinsic mechanical properties of the myocardium influence shear wave speed in vivo has not been extensively investigated. Purpose The aim of this study was to investigate the influence of clinical parameters as well as echocardiographic indicators of myocardial tissue properties and left ventricular (LV) filling pressures on shear wave propagation speed after MVC. Methods 219 subjects (59±17 years; 140 males) were included in the study. Of those, 49 were healthy volunteers, 25 were patients with cardiac amyloidosis, 42 with hypertrophic cardiomyopathy, 35 with hypertensive heart disease and 68 with coronary artery disease. Subjects were scanned with an experimental ultrasound scanner using diverging wave imaging to acquire images at a high temporal resolution (average frame rate: 1167±414 Hz). Shear waves after MVC were visualized on M-mode maps along the interventricular septum which were colour coded for tissue acceleration (Figure 1). The propagation speed was calculated by semi-automatically measuring the spatiotemporal slope of the shear wave. Univariate and multivariate linear regression analysis was performed to identify variables associated with shear wave propagation speed. Results Univariate regression analysis revealed an association of the following variables with shear wave speed: age, BMI, systolic blood pressure, E wave, average e', E/e', left atrial volume index (LAVI), grade of diastolic dysfunction, isovolumic relaxation time, septal wall thickness, LV wall mass and presence of cardiomyopathy. These variables were added to a multivariate model. Predictors of shear wave speed after MVC were BMI, E wave, average e', LAVI, LV wall mass and presence of cardiomyopathy (R2=0.53) (Table 1). Conclusions The results of this study indicate that both myocardial structural properties (reflected by predictors LV wall mass and presence of cardiomyopathy) and LV filling pressures (reflected by predictors E wave, average e' and LAVI) affect shear wave speed. These findings suggest that SWE has the potential to assess structural as well as functional changes to the LV, which should be further explored. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research foundation Flanders - FWO

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops

BackgroundShear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties. ObjectivesThis study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method. MethodsIn 15 pigs, conventional and high–frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury. ResultsShear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant β (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001). ConclusionsShear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

Quantification of changes in myocardial T1 * values with exercise cardiac MRI using a free-breathing non-electrocardiograph radial imaging.

To develop and evaluate a free breathing non-electrocardiograph (ECG) myocardial T1 * mapping sequence using radial imaging to quantify the changes in myocardial T1 * between rest and exercise (T1 *reactivity ) in exercise cardiac MRI (Ex-CMR). A free-running T1 * sequence was developed using a saturation pulse followed by three Look-Locker inversion-recovery experiments. Each Look-Locker continuously acquired data as radial trajectory using a low flip-angle spoiled gradient-echo readout. Self-navigation was performed with a temporal resolution of ∼100 ms for retrospectively extracting respiratory motion. The mid-diastole phase for every cardiac cycle was retrospectively detected on the recorded electrocardiogram signal using an empirical model. Multiple measurements were performed to obtain mean value to reduce effects from the free-breathing acquisition. Finally, data acquired at both mid-diastole and end-expiration are picked and reconstructed by a low-rank plus sparsity constraint algorithm. The performance of this sequence was evaluated by simulations, phantoms, and in vivo studies at rest and after physiological exercise. Numerical simulation demonstrated that changes in T1 * are related to the changes in T1 ; however, other factors such as breathing motion could influence T1 * measurements. Phantom T1 * values measured using free-running T1 * mapping sequence had good correlation with spin-echo T1 values and was insensitive to heart rate. In the Ex-CMR study, the measured T1 * reactivity was 10% immediately after exercise and declined over time. The free-running T1 * mapping sequence allows free-breathing non-ECG quantification of changes in myocardial T1 * with physiological exercise. Although, absolute myocardial T1 * value is sensitive to various confounders such as B1 and B0 inhomogeneity, quantification of its change may be useful in revealing myocardial tissue properties with exercise.