The value of left ventricular and left atrial strains in eosinophilic myocarditis and hypereosinophilic syndrome

Introduction

Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders distinguished by sustained peripheral or tissue hypereosinophilia with concurrent evidence of eosinophil-mediated organ damage (1,2). The current criteria for HES include an absolute eosinophil count greater than 1,500/µL on two examinations at least two weeks apart or an excess of eosinophils in the tissues or bone marrow on pathology and eosinophil-related organ damage (3). Activated eosinophils sometimes infiltrate into the myocardium and cause eosinophilic myocarditis (EM) (4). It is also referred to as Loeffler’s endocarditis in the chronic phase. After the acute phase with eosinophil infiltration of the endocardium, thrombus forms in the cardiac cavity in the second phase, and over time, eosinophil infiltration leads to the third phase of subendocardial fibrosis (4). Fibrosis can lead to restrictive cardiomyopathy with congestive heart failure. HES often causes organ damage in the lungs, skin, and gastrointestinal tract (5), but cardiac dysfunction and thromboembolism are the primary causes of death for patients with HES (6). While the mortality rate of HES has improved with advances in the management of HES (7), short-term deaths due to cardiogenic cerebral emboli (8) and sudden cardiac death (8,9) have been reported. Screening and early detection of cardiac involvement are an important part of HES management.

Echocardiography is mainly used to screen for cardiac complications in HES, such as endocardial thickening, mural thrombus, and restrictive cardiomyopathy (7,10). However, not all EM patients will present with these classic findings. Endomyocardial biopsy is considered the gold-standard diagnostic method for EM, and cardiovascular magnetic resonance (CMR) imaging can detect myocarditis better than echocardiography (11,12), but they are not always accessible. Left ventricular global longitudinal strain (LVGLS) is a sensitive measure of left ventricular (LV) systolic function and can detect clinically relevant LV dysfunction that cannot be captured by standard qualitative assessment (13). Left atrial (LA) strain is affected by LV diastolic dysfunction and closely related to LA remodeling and dysfunction (14). Right ventricular (RV) free wall strain is more sensitive for detecting RV systolic dysfunction than conventional echocardiographic parameters (15). These strain parameters may serve as imaging markers of restrictive cardiomyopathy, but the clinical value of strain imaging for screening and prognostication in patients with HES and EM remains not fully defined. We aimed to assess the relationship between strain imaging and outcomes in EM. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-287/rc).

Methods

Study design and setting

This is a single-center cross-sectional study. The institutional electronic medical record was queried to identify all echocardiograms performed at the Cleveland Clinic between September 1986 and January 2023 with eosinophilia. The identification of eosinophilia was based on the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes (D72.1). Patients with HES diagnosed according to the 2021 HES consensus document were included (3). Patients were excluded if they were younger than 18 years, and did not undergo echocardiography before treatment for HES. Data regarding medical history, comorbidities, management strategies, echocardiographic data, and hospital course were collected. We obtained follow-up data when available. EM was definitively diagnosed when endomyocardial biopsy demonstrated eosinophilic infiltration. When characteristic cardiac features, including endocardial wall thickening and LV thrombus (Figure 1), were observed on imaging during the course of HES, the diagnosis was confirmed using a comprehensive approach that integrated clinical symptoms and troponin measurements. The primary endpoint was composite events defined as stroke at diagnosis and major adverse cardiovascular events (MACE) during the follow-up period. MACE was defined as a composite of stroke, acute myocardial infarction, admission for heart failure, and cardiovascular death. We also analyzed subgroups by normal and worse LVGLS.

Figure 1 Echocardiographic findings of eosinophilic myocarditis in hypereosinophilic syndrome. (A) Endocardial thickening was observed extending from the base to the apex of the left ventricular wall (arrowheads); (B) a left ventricular thrombus was observed in contact with the thickened apical endocardium (arrowheads).

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the institutional review board of the Cleveland Clinic (IRB 20-1300). Due to retrospective nature of the study, patient consent was waived.

Echocardiographic assessment

All patients underwent transthoracic echocardiography at our center using the latest equipment available at the time of examination. We collected echocardiographic data on LV volume, wall thickness, LV ejection fraction using the Simpson method, and valve disease. In addition, diastolic function parameters such as E/A, E/e’, and RV systolic pressure were also collected. All measurements were performed according to the criteria set out in the current guidelines (16). LV diastolic function was evaluated referring to the latest guidelines by American Society of Echocardiography and the European Association of Cardiovascular Imaging (17). Assessment of global longitudinal strain was performed retrospectively during the study by blinded physicians using the vendor-neutral TOMTEC software (TOMTEC-ARENA TTA2; Philips Healthcare). LVGLS was calculated from apical four-, three- and two-chamber views, and the average LVGLS value was derived (Figure 2). The apical four-chamber view was used to evaluate LA strain and RV free wall strain (Figure 3). LVGLS, LA contraction strain, LA conduit strain and RV free wall strain were reported as negative values and LA reservoir strain as positive values. As there are no established cutoff values for abnormal LVGLS in EM among HES patients, we adopted the guideline-recommended threshold of −16% to dichotomize LVGLS values in this study (18).

Figure 2 Representative figure of LVGLS measurement. LVGLS, left ventricular global longitudinal strain.

Figure 3 Representative figure of RV free wall strain and various LA strain measurements. LA, left atrial; RV, right ventricular.

Statistical analysis

Comparisons were made between EM patients and non-EM patients. Normally distributed continuous parameters were presented as mean ± standard deviation, and skewed continuous parameters were expressed as median with interquartile range, defined as the range between the first and third quartiles. The Shapiro-Wilk test was used to evaluate for normally distributed data. Categorical data were presented as percentages. Differences were assessed by the unpaired t-test for continuous variables with normally distributed data, by the Mann-Whitney U test for continuous variables without normally distributed data, and by the chi-square test for categorical variables. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity of LVGLS for predicting outcomes. All statistical tests were 2-sided and P values of <0.05 were considered statistically significant. Statistical analysis was performed using SPSS version 25 (SPSS Inc., Chicago, IL, USA).

Results

Clinical characteristics

Of the 1,664 patients with eosinophilia, 34 patients with HES who underwent echocardiography before treatment were included. Five EM patients underwent endomyocardial biopsy, and eosinophils were detected in all cases. In addition, seven EM patients underwent CMR, and LV thrombus was detected in four cases, endocardial thickening in four cases, and delayed gadolinium enhancement in five cases. During the course of HES, one patient presented with LV thrombus in the absence of LV wall motion abnormalities and was clinically diagnosed with EM. The baseline characteristics are shown in Table 1. The mean age of the patients was 57±16 years, and 58.8% were female. The median follow-up period was 85 months (interquartile range, 41–145 months). Of 10 patients with EM, CMR was performed in eight patients (73%) and endomyocardial biopsy in six patients (55%). The most common comorbidities in the EM group were asthma and hyperlipidemia, and hypertension in the non-EM group. No patients had a prior history of heart failure and myocardial infarction. There were no significant differences in baseline characteristics between the two groups. Coronary angiography was performed in five EM patients and two non-EM patients, and no significant coronary artery lesions were identified in any of these patients.

Echocardiographic findings

Echocardiographic parameters are shown in Table 2. LV ejection fraction was similar in both groups (59% vs. 64%, P=0.69). There were no significant differences in LV diastolic function parameters, including E/A (1.0 vs. 0.9, P=0.57), E/e’ (17.3 vs. 9.9, P=0.11), LA volume index (28 vs. 28 mL/m², P=0.94) and RV systolic pressure (43 vs. 34 mmHg, P=0.13). Patients with EM had significantly worse LVGLS (−9.7% vs. −15.5%, P=0.001), LA reservoir strain (21.0% vs. 32.1%, P=0.02) and LA contraction strain (−9.7% vs. −19.2%, P<0.001) compared to patients without EM, but there was no significant difference in LA conduit strain (−11.3% vs. −12.8%, P=0.61) and RV free wall strain (−17.5% vs. −23.4%, P=0.08). In the EM group, 50.0% had endocardial thickening, and 30.0% had LV thrombus. Most cases of LV thrombus were in the apex, and one case of thrombus was found adjacent to the posterior mitral valve leaflet. RV thrombus occurred in one patient who also had LV thrombus. Moderate or greater mitral regurgitation and pericardial effusion were more frequently observed in the EM group (40.0% vs. 8.3%, P=0.03).

Outcomes

The outcomes are shown in Table 3. The median follow-up was 85 months. Out of 34 patients with HES, ten patients (29.4%) were diagnosed with EM and twelve patients (35.3%) developed the composite events. Patients with EM tended to have higher incidence of the composite events (60.0% vs. 25.0%, P=0.052), stroke at diagnosis (30.0% vs. 8.3%, P=0.10), MACE during follow-up (30.0% vs. 20.8%, P=0.57), although these differences were not statistically significant. Among patients who developed MACE, defined as a composite of stroke, acute myocardial infarction, heart failure hospitalization, and cardiovascular death, two in the EM group and one in the non-EM group experienced MACE within 6 months of follow-up. In contrast, the time to MACE for the other patients was longer than six years.

Prognostic impact of LVGLS

Patients were divided into two groups according to whether baseline LVGLS was worse than −16% or not, and their outcomes were compared (Table 4). Two patients were excluded from this subgroup analysis due to inadequate image quality for LVGLS assessment. All patients with EM (9/9, 100%) and half of patients without EM (12/23, 52%) had LVGLS worse than −16% at baseline. Patients with worse LVGLS had significantly higher incidence of composite events compared to patients with normal LVGLS (47.6% vs. 9.1%, P=0.03). All four patients who developed stroke at diagnosis and all three patients who developed MACE within 6 months of follow-up had worse baseline LVGLS. The prognostic utility of LVGLS for predicting adverse outcomes using a cut-off of −16% was assessed by ROC curve analysis. The analysis yielded an area under the curve of 0.737. The positive predictive value was 47.6%, while the negative predictive value was 90.9%.

Reproducibility of measurements

Twenty patients were randomly selected and measured by two independent observers on two different occasions. The intraclass correlation coefficient (ICC) for interobserver variability was 0.993 for LVGLS [standard error of measurement (SEM) 2.86%] and 0.995 for LA reservoir strain (SEM 2.68%). For intraobserver variability, the ICC was 0.999 for LVGLS (SEM 1.10%) and 0.998 for LA reservoir strain (SEM 1.67%).

Discussion

The main findings of the study were (I) approximately 30% of patients with HES who underwent echocardiography had EM; (II) patients with EM had significantly impaired baseline LVGLS and LA strain; (III) HES patients with worse LVGLS, regardless of whether they developed EM, had significantly higher incidence of composite events, defined as stroke at diagnosis and MACE during the follow-up period.

Echocardiography and HES

Loeffler’s endocarditis was first reported by Wilhelm Loeffler in 1936. It is a rare form of restrictive cardiomyopathy that results from endomyocardial infiltration of eosinophils resulting in fibrosis. In a previous report, wall thickening and LV enlargement were observed in many cases of EM (19). In this study, there was no statistically significant difference in LV size between the two groups. One reason to explain this apparent difference is the change in the diagnostic criteria for HES. Chusid et al. established the diagnostic criteria for HES in 1975 as eosinophilia lasting for more than 6 months (1), but in order to provide early treatment for HES, this was shortened to 1 month in 2012 (2), and to 2 weeks in 2021 (3). It has been reported that EM progresses over several months, divided into three stages: the acute phase, the thrombotic phase, and the fibrotic phase (20). Early diagnosis and early treatment may have shortened the duration of eosinophil exposure, suppressed LV fibrosis, and prevented the development of LV restrictive diastolic dysfunction. Previous reports have shown that three-dimensional transthoracic, transesophageal, and contrast-enhanced echocardiography can clearly detect LV thrombus and LV wall thickening, and are useful for diagnosis of EM (21,22). Patients with EM more frequently had moderate or greater MR in our study. Some cases have been reported mitral valve disease in HES (23,24).

Strain imaging in HES

Some reports have shown that LVGLS is useful for early detection and prognosis prediction of myocardial diseases (25-29). Kostakou et al. (26) reported that patients with acute myocarditis had significantly worse LVGLS despite having normal left ventricular ejection fraction (LVEF) (−16.5%±2.2% vs. −20.5%±1.3%, P<0.0001). Kasner et al. (27) also reported that the LVGLS was impaired in chronic myocarditis despite normal LVEF (−17.01%±2.42% vs. −19.39%±3.81%, P<0.001). In the diagnosis of acute myocarditis, moderate correlation has been reported between LVGLS and late gadolinium enhancement on CMR (30). LVGLS could be used as a diagnostic adjunct to CMR for diagnosis of EM. For the diagnosis of EM or Loeffler’s endocarditis, no threshold for abnormal LVGLS has been defined. In the latest American Heart Association guidelines, LVGLS of less than 16% has been proposed as a threshold for ventricular systolic function; therefore, we adopted this criterion (31). When LVGLS 18% was used as the cut-off point, no significant difference was observed between the two groups (Table S1). In this study, all patients with EM had abnormal baseline LVGLS, worse than the normal value of −16% (Figure 4). The prognostic performance of the examined parameter was evaluated, yielding an area under the curve of 0.737, indicating moderate predictive accuracy. The positive predictive value was 47.6%, whereas the negative predictive value was 90.9%. These results suggest that the normal LVGLS can reliably rule out future cardiovascular events, while an abnormal LVGLS does not necessarily guarantee event occurrence. Therefore, this parameter may be useful for screening and risk stratification, but its use as a standalone diagnostic tool is limited. Integration with other clinical information and complementary tests is recommended to improve prognostic assessment. In the non-EM group, the mean LVGLS was also below −16%, which may reflect subclinical myocardial damage or be partly attributable to the higher prevalence of hypertension in this group compared with the EM group.

Figure 4 The proportion of abnormal strain parameters in the study cohort. HES, hypereosinophilic syndrome; LA, left atrial; LVGLS, left ventricular global longitudinal strain; RV, right ventricular.

It should be noted that there was no significant difference in the incidence of composite events between EM patients and non-EM patients, but patients with worse LVGLS had significantly higher incidence of composite events compared to patients with normal LVGLS. It has been reported that LVGLS was strongly associated with MACE in immune checkpoint inhibitor-related myocarditis with either preserved or reduced EF (32). LVGLS may be an effective predictor of future cardiovascular events in HES patients.

Outcome and HES

Stroke incidence in HES has been estimated to be around 12% (33). Ono et al. (34) summarized 97 cases of stroke in HES patients and reported that the overall mortality rate was 11%, and multiple infarctions were observed in 80% of cases. Eosinophilia can result in elevated blood viscosity and eosinophil-derived substances can lead to hypercoagulability through other mechanisms (34). HES progresses in 4 to 6 weeks to a thrombotic stage that results from excessive release of tissue factors by the damaged tissue and from eosinophils, causing distant embolism (20,35). Thrombi are frequently detected in the LV on echocardiography or CMR, although deep vein thrombosis and isolated thrombi in cerebral vessels have also been reported (20). In this study, all patients who developed stroke had abnormal baseline LVGLS. If worsening of LVGLS correlates with myocardial damage due to long-term elevated eosinophil and progression to the thrombotic phase of HES, cardiac screening using LVGLS may lead to early detection of EM, and prediction and prevention of future stroke.

Clinical implications

This study is the first to measure and compare strain parameters in patients with HES and EM. Among the ten patients with EM, four demonstrated eosinophilic infiltration on endomyocardial biopsy but showed neither LV thrombus nor endocardial thickening on imaging studies. On the other hand, all EM patients had abnormal LVGLS. This suggests that LVGLS may be a useful screening tool for EM in HES patients. Definitive diagnosis of cardiac involvement in HES relies on histopathological diagnosis via endomyocardial biopsy, with CMR as an important adjunct imaging modality (36). It is difficult to perform endomyocardial biopsy or CMR imaging on all HES patients. LVGLS as a screening tool may lead to these advanced investigations, and reduce the number of missed diagnoses of EM. In addition, a truly multidisciplinary approach involving close collaboration among internists, clinical cardiologists, interventional cardiologists, cardiovascular radiologists, and pathologists is essential (37). Most patients who developed composite events had abnormal baseline LVGLS. This suggests that abnormal LVGLS may be a risk factor for future cardiovascular events in HES patients, regardless of whether the patient was diagnosed with EM.

Limitations

This is a retrospective study at a quaternary institution, where there may be potential bias in the selection of cases. Due to problems with electronic medical record coding, it is possible that certain cases were not captured. This study included patients suspected of hypereosinophilia between 1986 and 2023. During this interval, the diagnostic criteria for HES underwent two revisions, and echocardiographic techniques improved considerably. Although differences in the diagnostic criteria at the time of presentation may have resulted in missed cases during patient selection, all patients included in the analysis met the current diagnostic criteria. Endomyocardial biopsy was not performed in all patients, and it is possible that the clinical diagnosis based on imaging findings was misclassified. In this study, only patients who underwent echocardiography before treatment were included. This may have introduced selection bias toward patients at higher risk of cardiac disease.

Conclusions

Among HES patients in this study, all patients with EM had abnormal baseline LVGLS, and half of the patients without EM also had abnormal baseline LVGLS. Patients with abnormal LVGLS had a higher incidence of cardiovascular events compared to those with normal LVGLS. A large prospective cohort is desirable to determine whether LVGLS is useful for screening cardiac involvement and predicting prognosis in patients with HES.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-287/rc

Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-287/dss

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-287/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-287/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the institutional review board of the Cleveland Clinic (IRB 20-1300). Due to retrospective nature of the study, patient consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Chusid MJ, Dale DC, West BC, et al. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore) 1975;54:1-27. [Crossref] [PubMed]
2. Valent P, Klion AD, Horny HP, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 2012;130:607-612.e9. [Crossref] [PubMed]
3. Valent P, Klion AD, Roufosse F, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 2023;78:47-59. [Crossref] [PubMed]
4. Bondue A, Carpentier C, Roufosse F. Hypereosinophilic syndrome: considerations for the cardiologist. Heart 2022;108:164-71. [Crossref] [PubMed]
5. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 2009;124:1319-25.e3. [Crossref] [PubMed]
6. Podjasek JC, Butterfield JH. Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res 2013;37:392-5. [Crossref] [PubMed]
7. Mankad R, Bonnichsen C, Mankad S. Hypereosinophilic syndrome: cardiac diagnosis and management. Heart 2016;102:100-6. [Crossref] [PubMed]
8. Grigoryan M, Geisler SD, St Louis EK, et al. Cerebral arteriolar thromboembolism in idiopathic hypereosinophilic syndrome. Arch Neurol 2009;66:528-31. [Crossref] [PubMed]
9. Corradi D, Vaglio A, Maestri R, et al. Eosinophilic myocarditis in a patient with idiopathic hypereosinophilic syndrome: insights into mechanisms of myocardial cell death. Hum Pathol 2004;35:1160-3. [Crossref] [PubMed]
10. Ommen SR, Seward JB, Tajik AJ. Clinical and echocardiographic features of hypereosinophilic syndromes. Am J Cardiol 2000;86:110-3. [Crossref] [PubMed]
11. Syed IS, Martinez MW, Feng DL, et al. Cardiac magnetic resonance imaging of eosinophilic endomyocardial disease. Int J Cardiol 2008;126:e50-2. [Crossref] [PubMed]
12. Brambatti M, Matassini MV, Adler ED, et al. Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes. J Am Coll Cardiol 2017;70:2363-75. [Crossref] [PubMed]
13. Kalam K, Otahal P, Marwick TH. Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart 2014;100:1673-80. [Crossref] [PubMed]
14. Jain V, Ghosh R, Gupta M, et al. Contemporary narrative review on left atrial strain mechanics in echocardiography: cardiomyopathy, valvular heart disease and beyond. Cardiovasc Diagn Ther 2021;11:924-38. [Crossref] [PubMed]
15. Prihadi EA, van der Bijl P, Dietz M, et al. Prognostic Implications of Right Ventricular Free Wall Longitudinal Strain in Patients With Significant Functional Tricuspid Regurgitation. Circ Cardiovasc Imaging 2019;12:e008666. [Crossref] [PubMed]
16. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:1-39.e14. [Crossref] [PubMed]
17. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016;29:277-314. [Crossref] [PubMed]
18. Thomas JD, Edvardsen T, Abraham T, et al. Clinical Applications of Strain Echocardiography: A Clinical Consensus Statement From the American Society of Echocardiography Developed in Collaboration With the European Association of Cardiovascular Imaging of the European Society of Cardiology. J Am Soc Echocardiogr 2025;38:985-1020. [Crossref] [PubMed]
19. Parrillo JE, Borer JS, Henry WL, et al. The cardiovascular manifestations of the hypereosinophilic syndrome. Prospective study of 26 patients, with review of the literature. Am J Med 1979;67:572-82. [Crossref] [PubMed]
20. Ogbogu PU, Rosing DR, Horne MK 3rd. Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 2007;27:457-75. [Crossref] [PubMed]
21. Del Bene MR, Cappelli F, Rega L, et al. Characterization of Löeffler eosinophilic myocarditis by means of real time three-dimensional contrast-enhanced echocardiography. Echocardiography 2012;29:E62-6. [Crossref] [PubMed]
22. Hernandez CM, Arisha MJ, Ahmad A, et al. Usefulness of three-dimensional echocardiography in the assessment of valvular involvement in Loeffler endocarditis. Echocardiography 2017;34:1050-6. [Crossref] [PubMed]
23. Fuzellier JF, Chapoutot L, Torossian PF. Mitral valve repair in idiopathic hypereosinophilic syndrome. J Heart Valve Dis 2004;13:529-31. [PubMed]
24. Fuzellier JF, Chapoutot L, Torossian PF, et al. Mitral valve replacement in idiopathic eosinophilic endocarditis without peripheral eosinophilia. J Card Surg 2005;20:472-4. [Crossref] [PubMed]
25. Løgstrup BB, Nielsen JM, Kim WY, et al. Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis. Eur Heart J Cardiovasc Imaging 2016;17:1018-26. [Crossref] [PubMed]
26. Kostakou PM, Kostopoulos VS, Tryfou ES, et al. Subclinical left ventricular dysfunction and correlation with regional strain analysis in myocarditis with normal ejection fraction. A new diagnostic criterion. Int J Cardiol 2018;259:116-21. [Crossref] [PubMed]
27. Kasner M, Aleksandrov A, Escher F, et al. Multimodality imaging approach in the diagnosis of chronic myocarditis with preserved left ventricular ejection fraction (MCpEF): The role of 2D speckle-tracking echocardiography. Int J Cardiol 2017;243:374-8. [Crossref] [PubMed]
28. Hsiao JF, Koshino Y, Bonnichsen CR, et al. Speckle tracking echocardiography in acute myocarditis. Int J Cardiovasc Imaging 2013;29:275-84. [Crossref] [PubMed]
29. Meindl C, Paulus M, Poschenrieder F, et al. Patients with acute myocarditis and preserved systolic left ventricular function: comparison of global and regional longitudinal strain imaging by echocardiography with quantification of late gadolinium enhancement by CMR. Clin Res Cardiol 2021;110:1792-800. [Crossref] [PubMed]
30. Uppu SC, Shah A, Weigand J, et al. Two-dimensional speckle-tracking-derived segmental peak systolic longitudinal strain identifies regional myocardial involvement in patients with myocarditis and normal global left ventricular systolic function. Pediatr Cardiol 2015;36:950-9. [Crossref] [PubMed]
31. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022;145:e876-94. [Crossref] [PubMed]
32. Awadalla M, Mahmood SS, Groarke JD, et al. Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis. J Am Coll Cardiol 2020;75:467-78. [Crossref] [PubMed]
33. Sethi HS, Schmidley JW. Cerebral infarcts in the setting of eosinophilia: three cases and a discussion. Arch Neurol 2010;67:1275-7. [Crossref] [PubMed]
34. Ono R, Iwahana T, Kato H, et al. Literature reviews of stroke with hypereosinophilic syndrome. Int J Cardiol Heart Vasc 2021;37:100915. [Crossref] [PubMed]
35. Moosbauer C, Morgenstern E, Cuvelier SL, et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007;109:995-1002. [Crossref] [PubMed]
36. Reeder M, Okushi Y, Lo Presti Vega S, et al. The Cleveland Clinic experience of eosinophilic myocarditis in the setting of hypereosinophilic syndrome: demographics, cardiac imaging, and outcomes. Cardiovasc Diagn Ther 2024;14:1122-33. [Crossref] [PubMed]
37. Mapelli M, Volpi B, Agostoni P. Digging through eosinophils to identify cases of myocardial involvement-an effort well spent. Cardiovasc Diagn Ther 2025;15:1-4. [Crossref] [PubMed]