Segmental Strain Imaging as a Window into Preclinical Cardiac Dysfunction in LGMDR9

Segmental Strain Imaging as a Window into Preclinical Cardiac Dysfunction in LGMDR9 | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Echocardiography This is a preprint and has not been peer reviewed. Data may be preliminary. 19 May 2025 V1 Latest version Share on Segmental Strain Imaging as a Window into Preclinical Cardiac Dysfunction in LGMDR9 Authors : Noriaki Iwahashi 0000-0003-4810-3570 [email protected] , Tomohiro Yoshii , and Kiyoshi Hibi Authors Info & Affiliations https://doi.org/10.22541/au.174768322.25332058/v1 Published Echocardiography Version of record Peer review timeline 238 views 182 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The study by Caglayan et al. offers a significant advancement in our understanding of subclinical cardiac involvement in patients with limb-girdle muscular dystrophy R9 (LGMDR9). Utilizing speckle-tracking echocardiography (STE) and strain-rate imaging, the authors identify regional impairments in myocardial function—particularly in the apical segments—even in patients with preserved left ventricular ejection fraction. These findings underscore the importance of segmental myocardial analysis for early disease detection and risk stratification in neuromuscular cardiomyopathies. In this invited Commentary, we discuss the clinical and research implications of their work, highlight the diagnostic potential of strain-based imaging techniques, and advocate for broader implementation in the longitudinal management of patients with muscular dystrophies. We commend the authors for their methodologically sound approach and for drawing attention to the utility of advanced echocardiographic modalities in rare cardiomyopathies. Their contribution lays the groundwork for future research aimed at refining disease-specific imaging protocols and improving early intervention strategies. Segmental Strain Imaging as a Window into Preclinical Cardiac Dysfunction in LGMDR9 Authors: Noriaki Iwahashi 1 , Tomohiro Yoshii 1 , Kiyoshi Hibi 2 Affiliations: 1; Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan 2; Department of Cardiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan The study by Caglayan et al. represents an important and methodologically robust contribution to the evolving field of cardiac imaging in neuromuscular diseases, particularly limb-girdle muscular dystrophy R9 (LGMDR9). Employing speckle-tracking echocardiography (STE), the authors compellingly demonstrate subtle yet clinically meaningful impairments in left ventricular (LV) function, predominantly in the mid and apical segments, even in the presence of preserved ejection fraction (LVEF). Their findings offer a significant advance in the early detection and risk stratification of myocardial involvement in this rare disorder. STE has proven useful in detecting myocardial dysfunction across a wide range of cardiovascular conditions. 1,2 In particular, global longitudinal strain (GLS) has gained recognition as a sensitive marker of systolic function, especially in patients with preserved LVEF. 3 Previous studies have consistently shown that reduced GLS predicts adverse outcomes in various disease settings. 4,5 In addition to the LV function, STE enables us to evaluate left atrial function 6 , therefore the utility of STE is likely to expand further as technology and clinical applications advance. 7,8 Strain-rate (SR) imaging, another non-invasive modality, further enhances our ability to characterize myocardial mechanics. 9 Its ability to distinguish active from passive myocardial motion, and to quantify both systolic and diastolic components of myocardial function, makes it an invaluable complement to conventional echocardiographic evaluation. 10 Muscular dystrophies, particularly those involving sarcolemmal or glycosylation-related structural proteins, frequently result in cardiomyopathy and arrhythmias. 11,12 As alterations in myocardial motion often precede changes in ejection fraction, strain and strain-rate imaging may serve as sensitive tools for early cardiac risk stratification. In this context, the finding by Caglayan et al. that reduced apical motion may signal preclinical cardiomyopathy is both novel and clinically meaningful. Their results highlight the importance of regional myocardial analysis in LGMDR9, reinforcing the value of strain/SR imaging in the early detection of myocardial involvement, even in patients with preserved LVEF. Although LGMDR9 is a rare disease, this study includes one of the largest cohorts of LGMDR9 patients to date; nonetheless, the sample size remains limited. Thus, future research should aim to include more patients with LGMDR9 and expand to other types of muscular dystrophies to identify disease-specific cardiac features. Based on the findings of the present study, it is strongly anticipated that subsequent investigations will elucidate disease-specific imaging patterns and establish region-specific cutoff values, thereby enhancing diagnostic precision and clinical applicability. Dystrophinopathies include Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy, as well as DMD and BMD female carriers. The primary presenting symptom in most dystrophinopathies is skeletal muscle weakness. However, cardiac muscle is also a subtype of striated muscle and is similarly affected in many of the muscular dystrophies. 13 Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that presents in childhood, with cardiomyopathy becoming a major cause of morbidity and mortality as respiratory care improves and patient survival increases. 11 DMD-associated cardiomyopathy has distinct features compared to other pediatric dilated cardiomyopathies: there is typically less left ventricular (LV) dilation at diagnosis, fewer initial cardiac symptoms, and delayed initiation of treatment. In recent years, cardiac magnetic resonance imaging (CMR) has gained attention for its utility in assessing myocardial damage, which is a useful modality 14 . Pharmacological interventions—such as ACE inhibitors, angiotensin receptor blockers (ARBs), β-blockers, and mineralocorticoid receptor antagonists—have been recommended, with early initiation shown to delay cardiac dysfunction. However, echocardiography remains more accessible and easier to perform in clinical settings. This study may have demonstrated the value of using STE which includes strain and SR imaging to provide a more detailed assessment of cardiac function in patients with muscular dystrophy. In patients with muscular dystrophies, including LGMDR9, longitudinal follow-up using STE is expected to facilitate timely referral for cardiac MRI, enabling more detailed evaluation when appropriate. While the study by Caglayan et al. provides valuable insights into early cardiac involvement in LGMDR9, several key questions remain. Specifically, there is a need for larger, multi-center studies to validate these findings and to establish standardized STE protocols and normative values for this patient population. Furthermore, the long-term prognostic significance of the observed subclinical myocardial dysfunction and the optimal timing and type of interventions to prevent progression to overt heart failure require further investigation. Finally, comparative studies across different muscular dystrophy subtypes are warranted to identify unique cardiac phenotypes and inform tailored management strategies. These insights from Caglayan et al. are not only scientifically sound but carry important implications for clinical practice. Their contribution paves the way for more nuanced and personalized cardiac monitoring strategies in patients with muscular dystrophies—a significant step forward in the field of cardio-neuromuscular medicine. References 1. Li VW, So EK, Wong WH, et al.: Myocardial Deformation Imaging by Speckle-Tracking Echocardiography for Assessment of Cardiotoxicity in Children during and after Chemotherapy: A Systematic Review and Meta-Analysis. J Am Soc Echocardiogr. 2022:35: 629-656.2. Saccheri MC, Cianciulli TF, Lax JA, et al.: Two-dimensional speckle tracking echocardiography for early detection of myocardial damage in young patients with Fabry disease. Echocardiography. 2013:30: 1069-1077.3. Haugaa KH, Dejgaard LA: Global Longitudinal Strain: Ready for Clinical Use and Guideline Implementation. J Am Coll Cardiol. 2018:71: 1958-1959.4. Thavendiranathan P, Negishi T, Somerset E, et al.: Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy. J Am Coll Cardiol. 2021:77: 392-401.5. Iwahashi N, Horii M, Kirigaya J, et al.: Clinical Usefulness of the Serial Examination of Three-Dimensional Global Longitudinal Strain After the Onset of ST-Elevation Acute Myocardial Infarction. Circ J. 2022:86: 611-619.6. Tanasa A, Tapoi L, Ureche C, et al.: Left atrial strain: A novel ”biomarker” for chronic kidney disease patients? Echocardiography. 2021:38: 2077-2082.7. Iwahashi N, Gohbara M, Kirigaya J, et al.: Prognostic Significance of the Combination of Left Atrial Reservoir Strain and Global Longitudinal Strain Immediately After Onset of ST-Elevation Acute Myocardial Infarction. Circ J. 2022:86: 1499-1508.8. Loar RW, Pignatelli RH, Wilkinson JC, et al.: Strain Measures of Atrial and Ventricular Diastolic Function in Pediatric Fontan Patients: Comparisons to Controls and Between Ventricular Morphology Types. Echocardiography. 2025:42: e70133.9. Efe SC, Gurbuz AS, Ozturk S, et al.: Strain and strain rate echocardiography variables in adult Wilson’s disease patients: A speckle tracking echocardiography study. J Clin Ultrasound. 2020:48: 324-329.10. Dahl JS, Barros-Gomes S, Videbæk L, et al.: Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis. JACC Cardiovasc Imaging. 2016:9: 519-528.11. McNally EM, Kaltman JR, Benson DW, et al.: Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with Parent Project Muscular Dystrophy. Circulation. 2015:131: 1590-1598.12. Earl CC, Soslow JH, Markham LW, et al.: Myocardial strain imaging in Duchenne muscular dystrophy. Front Cardiovasc Med. 2022:9: 1031205.13. Kamdar F, Garry DJ: Dystrophin-Deficient Cardiomyopathy. J Am Coll Cardiol. 2016:67: 2533-2546.14. Starnes JR, Xu M, George-Durrett K, et al.: Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy. J Am Heart Assoc. 2024:13: e032960. Information & Authors Information Version history V1 Version 1 19 May 2025 Peer review timeline Published Echocardiography Version of Record 12 Jun 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Echocardiography Keyword strain strain-rate Authors Affiliations Noriaki Iwahashi 0000-0003-4810-3570 [email protected] Yokohama City University Medical Center View all articles by this author Tomohiro Yoshii View all articles by this author Kiyoshi Hibi Yokohama City Univ View all articles by this author Metrics & Citations Metrics Article Usage 238 views 182 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Noriaki Iwahashi, Tomohiro Yoshii, Kiyoshi Hibi. Segmental Strain Imaging as a Window into Preclinical Cardiac Dysfunction in LGMDR9. Authorea . 19 May 2025. DOI: https://doi.org/10.22541/au.174768322.25332058/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174768322.25332058/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffc2f03994ce2c5',t:'MTc3OTQ1NjcxMg=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();