Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to enhance the cardiac phenotype in the mdx model, many methods lead to high mortality, variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. For our study, mdx and wild-type (WT) mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathologic assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels, and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes, and diminished cardiac reserve in mdx mice compared to wild-type. Our findings highlight the utility of low-dose isoproterenol in mdx mice as a valuable model for exploring therapies targeting DMD-associated cardiac complications.

Echocardiographic strain analysis by speckle tracking allows assessment of myocardial deformation during the cardiac cycle. Its clinical applications have significantly expanded over the last two decades as a sensitive marker of myocardial dysfunction with important diagnostic and prognostic values. Strain analysis has the potential to become a routine part of the perioperative echocardiographic examination for most anesthesiologist-echocardiographers but its exact role in the perioperative setting is still being defined.
This clinical report reviews the principles underlying strain analysis and describes its main clinical uses pertinent to the field of anesthesiology and perioperative medicine. Strain for assessment of left and right ventricular function as well as atrial strain is described. We also discuss the potential role of strain to aid in perioperative risk stratification, surgical patient selection in cardiac surgery, and guidance of anesthetic monitor choice and clinical decision-making in the perioperative period.
Echocardiographic strain analysis is a powerful tool that allows seeing what conventional 2D imaging sometimes fails to reveal. It often provides pathophysiologic insight into various cardiac diseases at an early stage. Strain analysis is readily feasible and reproducible thanks to the use of highly automated software platforms. This technique shows promising potential to become a valuable tool in the arsenal of the anesthesiologist-echocardiographer and aid in perioperative risk-stratification and clinical decision-making.
RéSUMé: OBJECTIF: L’analyse échocardiographique de la déformation cardiaque (strain analysis) par suivi des marqueurs acoustiques (speckle-tracking) permet d’évaluer la déformation du myocarde au cours du cycle cardiaque. Ses applications cliniques se sont considérablement développées au cours des deux dernières décennies en tant que marqueur sensible du dysfonctionnement myocardique, avec des valeurs diagnostiques et pronostiques importantes. L’analyse de la déformation cardiaque a le potentiel de devenir une partie intégrante de l’examen échocardiographique périopératoire de routine pour la plupart des anesthésiologistes-échocardiographes, mais son rôle exact dans le cadre périopératoire est encore en cours de définition. CARACTéRISTIQUES CLINIQUES: Ce rapport clinique passe en revue les principes qui sous-tendent l’analyse de la déformation cardiaque et décrit ses principales utilisations cliniques pertinentes dans le domaine de l’anesthésiologie et de la médecine périopératoire. L’analyse de la déformation cardique pour l’évaluation de la fonction ventriculaire gauche et droite ainsi que de la déformation auriculaire sont décrites. Nous discutons également du rôle potentiel de l’analyse de la déformation cardiaque pour aider à la stratification du risque périopératoire, à la sélection des patients en chirurgie cardiaque, à l’orientation du choix des moniteurs anesthésiques, et à la prise de décision clinique en période périopératoire. CONCLUSION: L’analyse échocardiographique de la déformation cardiaque est un outil puissant qui permet de voir ce que l’imagerie 2D conventionnelle ne parvient parfois pas à révéler. Elle fournit souvent un aperçu physiopathologique de diverses maladies cardiaques à un stade précoce. L’analyse de la déformation cardiaque est facilement réalisable et reproductible grâce à l’utilisation de plateformes logicielles hautement automatisées. Cette technique est potentiellement prometteuse et pourrait devenir un outil précieux dans l’arsenal de l’anesthésiologiste-échocardiographe et aider à la stratification du risque périopératoire et à la prise de décision clinique.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation.
RICT was investigated in female C57BL/6J mice in which the base of the heart was irradiated under image-guidance using a small animal radiation research platform (SARRP). Mice were randomly assigned to a treatment group: single-fraction dose of 16 Gy or 20 Gy, 3 consecutive fractions of 8.66 Gy, or sham irradiation; biological effective doses (BED) used were 101.3 Gy, 153.3 Gy and 101.3 Gy respectively. Longitudinal transthoracic echocardiography (TTE) was performed from baseline up to 50 weeks post-irradiation to detect structural and functional effects.
Irradiation of the heart base leads to BED-dependent changes in systolic and diastolic function 50 weeks post-irradiation. GLS showed significant decreases in a BED-dependent manner for all irradiated animals, as early as 10 weeks after irradiation. Early changes in GLS indicate late changes in cardiac function. BED-independent increases were observed in the left ventricle (LV) mass and volume and myocardial fibrosis.
Functional features of RICT displayed a BED dependence in this study. GLS showed an early change at 10 weeks post-irradiation. Cardiac remodelling was observed as increases in mass and volume of the LV, further supporting our hypothesis that dose to the base of the heart drives the global heart toxicity.

Heart block (HB) is one of the most serious arrhythmias. Higher degrees of HB-for example, trifascicular HB-result in a more intense patient condition. Atrial septal defects (ASDs) represent the most common congenital heart disease in adults. All ASDs generally result in a left-to-right shunt, commonly causing right-side enlargement and dilation and, to a lesser extent, left atrial enlargement. A 26-year-old woman presented to the physician outpatient clinic with a complicated ASD with trifascicular HB and severe mitral and tricuspid regurgitations. The trifascicular HB with valvular regurgitations resolved with congenital ASD closure; however, she was diagnosed with coronavirus disease 2019 (COVID-19)-associated cardiac strain 3 years later. Interventions included electrocardiography, oxygenation, echocardiography, and cardiovascular surgical repair. A dramatic electrocardiographic response and better clinical outcomes despite dilations of both atria were observed. Trifascicular HB is a newly recorded association after congenital ASDs in adults. The disappearance of trifascicular HB after surgical closure of the congenital ASD is an indicator of effective surgical repair. The occurrence of COVID-19 pneumonia later, with atrial dilations continuing after the infection, may be a constellation of risk factors for the observed cardiac strain.

The diagnosis of heart failure usually includes a global functional assessment, such as ejection fraction measured by magnetic resonance imaging. However, these metrics have low discriminate power to distinguish different cardiomyopathies, which may not affect the global function of the heart. Quantifying local deformations in the form of cardiac strain can provide helpful information, but it remains a challenge. In this work, we introduce WarpPINN, a physics-informed neural network to perform image registration to obtain local metrics of heart deformation. We apply this method to cine magnetic resonance images to estimate the motion during the cardiac cycle. We inform our neural network of the near-incompressibility of cardiac tissue by penalizing the Jacobian of the deformation field. The loss function has two components: an intensity-based similarity term between the reference and the warped template images, and a regularizer that represents the hyperelastic behavior of the tissue. The architecture of the neural network allows us to easily compute the strain via automatic differentiation to assess cardiac activity. We use Fourier feature mappings to overcome the spectral bias of neural networks, allowing us to capture discontinuities in the strain field. The algorithm is tested on synthetic examples and on a cine SSFP MRI benchmark of 15 healthy volunteers, where it is trained to learn the deformation mapping of each case. We outperform current methodologies in landmark tracking and provide physiological strain estimations in the radial and circumferential directions. WarpPINN provides precise measurements of local cardiac deformations that can be used for a better diagnosis of heart failure and can be used for general image registration tasks. Source code is available at https://github.com/fsahli/WarpPINN.

BACKGROUND: Hindered by its unspecific clinical and phenotypical presentation, cardiac sarcoidosis (CS) remains a challenging diagnosis.
OBJECTIVE: Utilizing cardiac magnetic resonance imaging (CMR), we acquired multi-chamber volumetrics and strain feature tracking for a support vector machine learning (SVM)-based diagnostic approach to CS.
METHODS: Forty-five CMR-negative (CMR(-), 56.5(53.0;63.0)years), eighteen CMR-positive (CMR(+), 64.0(57.8;67.0)years) sarcoidosis patients and forty-four controls (CTRL, 56.5(53.0;63.0)years)) underwent CMR examination. Cardiac parameters were processed using the classifiers of logistic regression, KNN(K-nearest-neighbor), DT (decision tree), RF (random forest), SVM, GBoost, XGBoost, Voting and feature selection.
RESULTS: In a three-cluster analysis of CTRL versus vs. CMR(+) vs. CMR(-), RF and Voting classifier yielded the highest prediction rates (81.82%). The two-cluster analysis of CTRL vs. all sarcoidosis (All Sarc.) yielded high prediction rates with the classifiers logistic regression, RF and SVM (96.97%), and low prediction rates for the analysis of CMR(+) vs. CMR(-), which were augmented using feature selection with logistic regression (89.47%).
CONCLUSIONS: Multi-chamber cardiac function and strain-based supervised machine learning provides a non-contrast approach to accurately differentiate between healthy individuals and sarcoidosis patients. Feature selection overcomes the algorithmically challenging discrimination between CMR(+) and CMR(-) patients, yielding high accuracy predictions. The study findings imply higher prevalence of cardiac involvement than previously anticipated, which may impact clinical disease management.

UNASSIGNED: Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity.
UNASSIGNED: Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography.
UNASSIGNED: In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice (p = 0.043, p = 0.042, p = 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls.
UNASSIGNED: Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.

UNASSIGNED: Lathe machine work is an important unorganized sector in India. However, to date, no work physiological studies have been conducted among these workers to evaluate the physical strain involved in this work.
UNASSIGNED: The present study aims to determine the workload in different lathe machine tasks from working heart rates (HRs) and certain cardiac indices.
UNASSIGNED: A cross-sectional study was conducted among 38 full-time male workers aged between 21 and 60 years.
UNASSIGNED: The HR was measured directly during the productive work phase, additional work phase, and work pauses. Two cardiac strain indices, viz., net cardiac cost and relative cardiac cost were derived. The workload was also judged according to some standard acceptable criteria of physical strain.
UNASSIGNED: Mean and standard deviation were obtained for different categories of HR. Intergroup comparisons were conducted through one-way analysis of variance and the t-test.
UNASSIGNED: The mean working HR was found to be 99 beats per minute. A maximal working HR of 105 ± 6.1 beats per minute with a corresponding relative cardiac cost of 26% was obtained during the additional work phase.
UNASSIGNED: The overall workload appeared to be moderate in nature. An acceptable criterion of cardiac cost of 30% appeared to be the most sensitive index in detecting workers experiencing a higher level of physical strain.

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model. We now show that gene therapy using a micro-dystrophin optimized for skeletal muscle efficacy (AAV-μDys5), and which is currently in a clinical trial, is able to fully prevent cardiac pathology and cardiac strain abnormalities and maintain normal (>45%) ejection fraction through 18 months of age in Fiona/dko mice. Early treatment with AAV-μDys5 prevents inflammation and fibrosis in Fiona/dko hearts. Collagen in cardiac fibrotic scars becomes more tightly packed from 12 to 18 months in Fiona/dko mice, but the area of fibrosis containing tenascin C does not change. Increased tight collagen correlates with unexpected improvements in Fiona/dko whole-heart function that maintain impaired cardiac strain and strain rate. This study supports micro-dystrophin gene therapy as a promising intervention for preventing DMD cardiomyopathy progression.