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Published in: Insights into Imaging 1/2023

Open Access 01-12-2023 | Cardiomyopathy | Original Article

Late gadolinium enhancement entropy as a new measure of myocardial tissue heterogeneity for prediction of adverse cardiac events in patients with hypertrophic cardiomyopathy

Authors: Zi-Yi Gu, Yu-Fan Qian, Bing-Hua Chen, Chong-Wen Wu, Lei Zhao, Song Xue, Lei Zhao, Lian-Ming Wu, Yong-Yi Wang

Published in: Insights into Imaging | Issue 1/2023

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Abstract

Objectives

Entropy is a new late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR)–derived parameter that is independent of signal intensity thresholds. Entropy can be used to measure myocardial tissue heterogeneity by comparing full pixel points of tissue images. This study investigated the incremental prognostic value of left ventricular (LV) entropy in patients with hypertrophic cardiomyopathy (HCM).

Methods

This study enrolled 337 participants with HCM who underwent 3.0-T CMR. The LV entropy was obtained by calculating the probability distribution of the LV myocardial pixel signal intensities of the LGE sequence. Patients who underwent CMR imaging were followed up for endpoints. The primary endpoint was defined as readmission to the hospital owing to heart failure. The secondary endpoint was the composite of the primary endpoint, sudden cardiac death and non-cardiovascular death.

Results

During the median follow-up of 24 months ± 13 (standard deviation), 43 patients who reached the primary and secondary endpoints had a higher entropy (6.20 ± 0.45, p < 0.001). The patients with increased entropy (≥ 5.587) had a higher risk of the primary and secondary endpoints, compared with HCM patients with low entropy (p < 0.001 for both). In addition, Cox analysis showed that LV entropy provided significant prognostic value for predicting both primary and secondary endpoints (HR: 1.291 and 1.273, all p < 0.001). Addition of LV entropy to the multivariable model improved model performance and risk reclassification (p < 0.05).

Conclusion

LV entropy assessed by CMR was an independent predictor of primary and secondary endpoints. LV entropy assessment contributes to improved risk stratification in patients with HCM.

Critical relevance statement

Myocardial heterogeneity reflected by entropy the derived parameter of LGE has prognostic value for adverse events in HCM. The measurement of LV entropy helped to identify patients with HCM who were at risk for heart failure and sudden cardiac death.

Key points

• Left ventricular entropy can reflect myocardial heterogeneity in HCM patients.
• Left ventricular entropy was significantly higher in HCM patients who reached endpoint events.
• Left ventricular entropy helps to predict the occurrence of heart failure and death in HCM patients.

Graphical Abstract

Appendix
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Literature
2.
go back to reference McKenna WJ, Judge DP (2021) Epidemiology of the inherited cardiomyopathies. Nat Rev Cardiol 18(1):22–36CrossRefPubMed McKenna WJ, Judge DP (2021) Epidemiology of the inherited cardiomyopathies. Nat Rev Cardiol 18(1):22–36CrossRefPubMed
4.
5.
go back to reference Shi R, Shi K, Huang S et al (2022) Association between heart failure with preserved left ventricular ejection fraction and impaired left atrial phasic function in hypertrophic cardiomyopathy: evaluation by cardiac MRI feature tracking. J Magn Reson Imaging 56(1):248–259CrossRefPubMed Shi R, Shi K, Huang S et al (2022) Association between heart failure with preserved left ventricular ejection fraction and impaired left atrial phasic function in hypertrophic cardiomyopathy: evaluation by cardiac MRI feature tracking. J Magn Reson Imaging 56(1):248–259CrossRefPubMed
6.
go back to reference Ommen SR, Mital S, Burke MA et al (2020) 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. J Am Coll Cardiol 76(25):3022–3055CrossRefPubMed Ommen SR, Mital S, Burke MA et al (2020) 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. J Am Coll Cardiol 76(25):3022–3055CrossRefPubMed
7.
go back to reference Marian AJ, Braunwald E (2017) Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 121(7):749–770CrossRefPubMedPubMedCentral Marian AJ, Braunwald E (2017) Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 121(7):749–770CrossRefPubMedPubMedCentral
8.
go back to reference Wang J, Li Y, Yang F et al (2021) Fractal analysis: prognostic value of left ventricular trabecular complexity cardiovascular MRI in participants with hypertrophic cardiomyopathy. Radiology 298(1):71–79CrossRefPubMed Wang J, Li Y, Yang F et al (2021) Fractal analysis: prognostic value of left ventricular trabecular complexity cardiovascular MRI in participants with hypertrophic cardiomyopathy. Radiology 298(1):71–79CrossRefPubMed
9.
go back to reference Sultan FAT, Saadia S (2021) Patterns of left ventricular hypertrophy and late gadolinium enhancement on cardiac MRI in patients with hypertrophic cardiomyopathy and their prognostic significance—an experience from a South Asian Country. J Clin Imaging Sci 11(14) Sultan FAT, Saadia S (2021) Patterns of left ventricular hypertrophy and late gadolinium enhancement on cardiac MRI in patients with hypertrophic cardiomyopathy and their prognostic significance—an experience from a South Asian Country. J Clin Imaging Sci 11(14)
10.
go back to reference Ozawa K, Funabashi N, Takaoka H et al (2017) Successful MACE risk stratification in hypertrophic cardiomyopathy patients using different 2D speckle-tracking TTE approaches. Int J Cardiol 228:1015–1021CrossRefPubMed Ozawa K, Funabashi N, Takaoka H et al (2017) Successful MACE risk stratification in hypertrophic cardiomyopathy patients using different 2D speckle-tracking TTE approaches. Int J Cardiol 228:1015–1021CrossRefPubMed
11.
go back to reference Chan RH, Maron BJ, Olivotto I et al (2014) Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 130(6):484–495CrossRefPubMed Chan RH, Maron BJ, Olivotto I et al (2014) Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation 130(6):484–495CrossRefPubMed
12.
go back to reference Olivotto I, Maron MS, Autore C et al (2008) Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 52(7):559–566CrossRefPubMed Olivotto I, Maron MS, Autore C et al (2008) Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 52(7):559–566CrossRefPubMed
13.
go back to reference Reichek N, Gupta D (2008) Hypertrophic cardiomyopathy: cardiac magnetic resonance imaging changes the paradigm. J Am Coll Cardiol 52(7):567–568CrossRefPubMed Reichek N, Gupta D (2008) Hypertrophic cardiomyopathy: cardiac magnetic resonance imaging changes the paradigm. J Am Coll Cardiol 52(7):567–568CrossRefPubMed
14.
go back to reference Funada A, Kanzaki H, Noguchi T et al (2016) Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction. Heart Vessels 31(5):758–770CrossRefPubMed Funada A, Kanzaki H, Noguchi T et al (2016) Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction. Heart Vessels 31(5):758–770CrossRefPubMed
15.
go back to reference Green JJ, Berger JS, Kramer CM et al (2012) Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 5(4):370–377CrossRefPubMed Green JJ, Berger JS, Kramer CM et al (2012) Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 5(4):370–377CrossRefPubMed
16.
go back to reference Weng Z, Yao J, Chan RH et al (2016) Prognostic value of LGE-CMR in HCM: a meta-analysis. JACC Cardiovasc Imaging 9(12):1392–1402CrossRefPubMed Weng Z, Yao J, Chan RH et al (2016) Prognostic value of LGE-CMR in HCM: a meta-analysis. JACC Cardiovasc Imaging 9(12):1392–1402CrossRefPubMed
17.
go back to reference Di Marco A, Anguera I, Schmitt M et al (2017) Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC Heart Fail 5(1):28–38CrossRefPubMed Di Marco A, Anguera I, Schmitt M et al (2017) Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC Heart Fail 5(1):28–38CrossRefPubMed
18.
go back to reference Antiochos P, Ge Y, van der Geest RJ et al (2022) Entropy as a measure of myocardial tissue heterogeneity in patients with ventricular arrhythmias. JACC Cardiovasc Imaging 15(5):783–792CrossRefPubMed Antiochos P, Ge Y, van der Geest RJ et al (2022) Entropy as a measure of myocardial tissue heterogeneity in patients with ventricular arrhythmias. JACC Cardiovasc Imaging 15(5):783–792CrossRefPubMed
19.
go back to reference Wang L, Peng L, Zhao X et al (2023) Prognostic value of entropy derived from late gadolinium enhancement images to adverse cardiac events in post-myocardial infarction patients. Acad Radiol 30(2):239–247CrossRefPubMed Wang L, Peng L, Zhao X et al (2023) Prognostic value of entropy derived from late gadolinium enhancement images to adverse cardiac events in post-myocardial infarction patients. Acad Radiol 30(2):239–247CrossRefPubMed
20.
go back to reference Androulakis AFA, Zeppenfeld K, Paiman EHM et al (2019) Entropy as a novel measure of myocardial tissue heterogeneity for prediction of ventricular arrhythmias and mortality in post-infarct patients. JACC Clin Electrophysiol 5(4):480–489CrossRefPubMed Androulakis AFA, Zeppenfeld K, Paiman EHM et al (2019) Entropy as a novel measure of myocardial tissue heterogeneity for prediction of ventricular arrhythmias and mortality in post-infarct patients. JACC Clin Electrophysiol 5(4):480–489CrossRefPubMed
21.
go back to reference Muthalaly RG, Kwong RY, John RM et al (2019) Left ventricular entropy is a novel predictor of arrhythmic events in patients with dilated cardiomyopathy receiving defibrillators for primary prevention. JACC Cardiovasc Imaging 12(7 Pt 1):1177–1184CrossRefPubMed Muthalaly RG, Kwong RY, John RM et al (2019) Left ventricular entropy is a novel predictor of arrhythmic events in patients with dilated cardiomyopathy receiving defibrillators for primary prevention. JACC Cardiovasc Imaging 12(7 Pt 1):1177–1184CrossRefPubMed
23.
go back to reference Authors/Task Force m, Elliott PM, Anastasakis A et al (2014) 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 35(39):2733-2779 Authors/Task Force m, Elliott PM, Anastasakis A et al (2014) 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 35(39):2733-2779
24.
go back to reference Maron BJ (2010) Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation 121(3):445–456CrossRefPubMed Maron BJ (2010) Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation 121(3):445–456CrossRefPubMed
25.
go back to reference Maron MS, Maron BJ, Harrigan C et al (2009) Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 54(3):220–228CrossRefPubMed Maron MS, Maron BJ, Harrigan C et al (2009) Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 54(3):220–228CrossRefPubMed
26.
go back to reference Hinojar R, Fernández-Golfín C, González-Gómez A et al (2017) Prognostic implications of global myocardial mechanics in hypertrophic cardiomyopathy by cardiovascular magnetic resonance feature tracking. Relations to left ventricular hypertrophy and fibrosis. Int J Cardiol 249:467–472CrossRefPubMed Hinojar R, Fernández-Golfín C, González-Gómez A et al (2017) Prognostic implications of global myocardial mechanics in hypertrophic cardiomyopathy by cardiovascular magnetic resonance feature tracking. Relations to left ventricular hypertrophy and fibrosis. Int J Cardiol 249:467–472CrossRefPubMed
27.
go back to reference Kramer CM, Neubauer S (2018) Further refining risk in hypertrophic cardiomyopathy with late gadolinium enhancement by CMR. J Am Coll Cardiol 72(8):871–873CrossRefPubMedPubMedCentral Kramer CM, Neubauer S (2018) Further refining risk in hypertrophic cardiomyopathy with late gadolinium enhancement by CMR. J Am Coll Cardiol 72(8):871–873CrossRefPubMedPubMedCentral
28.
go back to reference Maron BJ, Rowin EJ, Casey SA et al (2016) How hypertrophic cardiomyopathy became a contemporary treatable genetic disease with low mortality: shaped by 50 years of clinical research and practice. JAMA Cardiol 1(1):98–105CrossRefPubMed Maron BJ, Rowin EJ, Casey SA et al (2016) How hypertrophic cardiomyopathy became a contemporary treatable genetic disease with low mortality: shaped by 50 years of clinical research and practice. JAMA Cardiol 1(1):98–105CrossRefPubMed
29.
go back to reference Hennig A, Salel M, Sacher F et al (2018) High-resolution three-dimensional late gadolinium-enhanced cardiac magnetic resonance imaging to identify the underlying substrate of ventricular arrhythmia. Europace 20(Fi2):f179–f191CrossRefPubMed Hennig A, Salel M, Sacher F et al (2018) High-resolution three-dimensional late gadolinium-enhanced cardiac magnetic resonance imaging to identify the underlying substrate of ventricular arrhythmia. Europace 20(Fi2):f179–f191CrossRefPubMed
30.
go back to reference Choudhury L, Mahrholdt H, Wagner A et al (2002) Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 40(12):2156–2164CrossRefPubMed Choudhury L, Mahrholdt H, Wagner A et al (2002) Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 40(12):2156–2164CrossRefPubMed
31.
go back to reference Moon JC, McKenna WJ, McCrohon JA et al (2003) Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am Coll Cardiol 41(9):1561–1567CrossRefPubMed Moon JC, McKenna WJ, McCrohon JA et al (2003) Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. J Am Coll Cardiol 41(9):1561–1567CrossRefPubMed
32.
go back to reference Gulati A, Jabbour A, Ismail TF et al (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309(9):896–908CrossRefPubMed Gulati A, Jabbour A, Ismail TF et al (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309(9):896–908CrossRefPubMed
33.
go back to reference Díez J, González A, Kovacic JC (2020) Myocardial interstitial fibrosis in nonischemic heart disease, part 3/4: JACC focus seminar. J Am Coll Cardiol 75(17):2204–2218CrossRefPubMedPubMedCentral Díez J, González A, Kovacic JC (2020) Myocardial interstitial fibrosis in nonischemic heart disease, part 3/4: JACC focus seminar. J Am Coll Cardiol 75(17):2204–2218CrossRefPubMedPubMedCentral
34.
go back to reference Galati G, Leone O, Pasquale F et al (2016) Histological and histometric characterization of myocardial fibrosis in end-stage hypertrophic cardiomyopathy: a clinical-pathological study of 30 explanted hearts. Circ Heart Fail 9(9): Galati G, Leone O, Pasquale F et al (2016) Histological and histometric characterization of myocardial fibrosis in end-stage hypertrophic cardiomyopathy: a clinical-pathological study of 30 explanted hearts. Circ Heart Fail 9(9):
35.
go back to reference Wu KC (2017) Sudden cardiac death substrate imaged by magnetic resonance imaging: from investigational tool to clinical applications. Circ Cardiovasc Imaging 10(7) Wu KC (2017) Sudden cardiac death substrate imaged by magnetic resonance imaging: from investigational tool to clinical applications. Circ Cardiovasc Imaging 10(7)
36.
go back to reference Amano Y, Suzuki Y, Yanagisawa F et al (2018) Relationship between extension or texture features of late gadolinium enhancement and ventricular tachyarrhythmias in hypertrophic cardiomyopathy. Biomed Res Int 2018:4092469CrossRefPubMedPubMedCentral Amano Y, Suzuki Y, Yanagisawa F et al (2018) Relationship between extension or texture features of late gadolinium enhancement and ventricular tachyarrhythmias in hypertrophic cardiomyopathy. Biomed Res Int 2018:4092469CrossRefPubMedPubMedCentral
37.
go back to reference Wu KC, Chrispin J (2022) More than meets the eye: cardiac magnetic resonance image entropy and ventricular arrhythmia risk prediction. JACC Cardiovasc Imaging 15(5):793–795CrossRefPubMedPubMedCentral Wu KC, Chrispin J (2022) More than meets the eye: cardiac magnetic resonance image entropy and ventricular arrhythmia risk prediction. JACC Cardiovasc Imaging 15(5):793–795CrossRefPubMedPubMedCentral
Metadata
Title
Late gadolinium enhancement entropy as a new measure of myocardial tissue heterogeneity for prediction of adverse cardiac events in patients with hypertrophic cardiomyopathy
Authors
Zi-Yi Gu
Yu-Fan Qian
Bing-Hua Chen
Chong-Wen Wu
Lei Zhao
Song Xue
Lei Zhao
Lian-Ming Wu
Yong-Yi Wang
Publication date
01-12-2023
Publisher
Springer Vienna
Published in
Insights into Imaging / Issue 1/2023
Electronic ISSN: 1869-4101
DOI
https://doi.org/10.1186/s13244-023-01479-6

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