Coronary Microvascular Dysfunction and Adverse Outcomes in the Spectrum of Dilated Cardiomyopathy

Hypokinetic non-dilated cardiomyopathy (HNDC), a preclinical state of dilated cardiomyopathy (DCM), is characterized by left ventricular (LV) dysfunction without LV dilatation. Although myocardial fibrosis and microvascular dysfunction in DCM are associated with LV remodeling and poor outcome, these...

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Published inInternational Heart Journal Vol. 66; no. 2; pp. 257 - 263
Main Authors Fujita, Yasuhiro, Kosuge, Hisanori, Hida, Satoshi, Satomi, Kazuhiro, Hachiya, Shoko, Kobayashi, Masatake
Format Journal Article
LanguageEnglish
Published Japan International Heart Journal Association 31.03.2025
Japan Science and Technology Agency
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ISSN1349-2365
1349-3299
DOI10.1536/ihj.24-744

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Abstract Hypokinetic non-dilated cardiomyopathy (HNDC), a preclinical state of dilated cardiomyopathy (DCM), is characterized by left ventricular (LV) dysfunction without LV dilatation. Although myocardial fibrosis and microvascular dysfunction in DCM are associated with LV remodeling and poor outcome, these characteristics concerning HNDC remain unclear. We compared DCM and HNDC with regard to their clinical characteristics and prognosis.We retrospectively enrolled 100 patients with DCM (n = 64) or HNDC (n = 36) who underwent cardiac magnetic resonance (CMR). DCM and HNDC were classified based on an LV end-diastolic diameter index (LVEDDI). The association of LVEDDI with the composite outcome of all-cause mortality, heart failure hospitalization, or ventricular arrhythmia occurrence was assessed. Phase-contrast cine imaging was performed in a subset of 17 patients (12 with DCM and 5 with HNDC) and 7 control subjects to assess coronary flow reserve (CFR).During the follow-up period (median: 22.0 months; interquartile range: 9.0-33.8 months), patients with DCM showed higher risk of the primary outcome than those with HNDC (P = 0.026). A higher LVEDDI was significantly associated with clinical outcomes even after adjusting for covariates (i.e., brain natriuretic peptide, the presence of late gadolinium enhancement, and LV ejection fraction; adjusted hazard ratio, 1.350; 95% confidence interval, 1.008-1.808; P = 0.044). CFR in HNDC was significantly higher than that in DCM (P < 0.05) and comparable to that in the control group.LV dilatation is an independent predictor of adverse events in DCM and HNDC.
AbstractList Hypokinetic non-dilated cardiomyopathy (HNDC), a preclinical state of dilated cardiomyopathy (DCM), is characterized by left ventricular (LV) dysfunction without LV dilatation. Although myocardial fibrosis and microvascular dysfunction in DCM are associated with LV remodeling and poor outcome, these characteristics concerning HNDC remain unclear. We compared DCM and HNDC with regard to their clinical characteristics and prognosis.We retrospectively enrolled 100 patients with DCM (n = 64) or HNDC (n = 36) who underwent cardiac magnetic resonance (CMR). DCM and HNDC were classified based on an LV end-diastolic diameter index (LVEDDI). The association of LVEDDI with the composite outcome of all-cause mortality, heart failure hospitalization, or ventricular arrhythmia occurrence was assessed. Phase-contrast cine imaging was performed in a subset of 17 patients (12 with DCM and 5 with HNDC) and 7 control subjects to assess coronary flow reserve (CFR).During the follow-up period (median: 22.0 months; interquartile range: 9.0-33.8 months), patients with DCM showed higher risk of the primary outcome than those with HNDC (P = 0.026). A higher LVEDDI was significantly associated with clinical outcomes even after adjusting for covariates (i.e., brain natriuretic peptide, the presence of late gadolinium enhancement, and LV ejection fraction; adjusted hazard ratio, 1.350; 95% confidence interval, 1.008-1.808; P = 0.044). CFR in HNDC was significantly higher than that in DCM (P < 0.05) and comparable to that in the control group.LV dilatation is an independent predictor of adverse events in DCM and HNDC.
ArticleNumber 24-744
Author Satomi, Kazuhiro
Kosuge, Hisanori
Fujita, Yasuhiro
Hida, Satoshi
Hachiya, Shoko
Kobayashi, Masatake
Author_xml – sequence: 1
  fullname: Fujita, Yasuhiro
  organization: Department of Cardiology, Tokyo Medical University
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  fullname: Kosuge, Hisanori
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  fullname: Hida, Satoshi
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  fullname: Satomi, Kazuhiro
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  fullname: Hachiya, Shoko
  organization: Department of Cardiology, Tokyo Medical University
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  fullname: Kobayashi, Masatake
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References_xml – reference: 11. Orphanou N, Papatheodorou E, Anastasakis A. Dilated cardiomyopathy in the era of precision medicine: latest concepts and developments. Heart Fail Rev 2022; 27: 1173-91.
– reference: 18. Karamitsos TD, Arvanitaki A, Karvounis H, et al. Myocardial Tissue Characterization and Fibrosis by Imaging. JACC Cardiovasc Imaging 2020; 13: 1221-34.
– reference: 20. Kato S, Saito N, Nakachi T, et al. Stress Perfusion Coronary Flow Reserve Versus Cardiac Magnetic Resonance for Known or Suspected CAD. J Am Coll Cardiol 2017; 70: 869-79.
– reference: 2. Puntmann VO, Voigt T, Chen Z, et al. Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. JACC Cardiovasc Imaging 2013; 6: 475-84.
– reference: 9. Kan A, Leng Y, Li S, et al. The predictive value of coronary microvascular dysfunction for left ventricular reverse remodelling in dilated cardiomyopathy. Front Cardiovasc Med 2023; 10: 1301509.
– reference: 24. Mohammed SF, Hussain S, Mirzoyev SA, et al. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation 2015; 131: 550-9.
– reference: 10. Pinto YM, Elliott PM, Arbustini E, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J 2016; 37: 1850-8.
– reference: 13. Mombeini H, Parsaee M, Amin A. Speckle tracking echocardiography in hypokinetic non-dilated cardiomyopathy: comparison with dilated cardiomyopathy. ESC Heart Fail 2020; 7: 1909-16.
– reference: 23. Yang Z, Liu Y, Li Z, et al. Coronary microvascular dysfunction and cardiovascular disease: Pathogenesis, associations and treatment strategies. Biomed Pharmacother 2023; 164: 115011.
– reference: 16. Kitaoka H, Matsumura Y, Yamasaki N, et al. Long-term prognosis of patients with mildly dilated cardiomyopathy. Circ J 2002; 66: 557-60.
– reference: 12. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023; 44: 3503-626.
– reference: 15. Nakamori S, Sakuma H, Dohi K, et al. Combined Assessment of Stress Myocardial Perfusion Cardiovascular Magnetic Resonance and Flow Measurement in the Coronary Sinus Improves Prediction of Functionally Significant Coronary Stenosis Determined by Fractional Flow Reserve in Multivessel Disease. J Am Heart Assoc 2018; 7: e007736.
– reference: 14. Verdonschot JAJ, Hazebroek MR, Wang P, et al. Clinical Phenotype and Genotype Associations With Improvement in Left Ventricular Function in Dilated Cardiomyopathy. Circ Heart Fail 2018; 11: e005220.
– reference: 3. Rubiś PP, Dziewięcka EM, Banyś P, et al. Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy. Sci Rep 2021; 11: 24000.
– reference: 4. Petersen SE, Jerosch-Herold M, Hudsmith LE, et al. Evidence for microvascular dysfunction in hypertrophic cardiomyopathy: new insights from multiparametric magnetic resonance imaging. Circulation 2007; 115: 2418-25.
– reference: 8. Gulati A, Ismail TF, Ali A, et al. Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study. JACC Cardiovasc Imaging 2019; 12: 1699-708.
– reference: 17. Mewton N, Liu CY, Croisille P, et al. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 2011; 57: 891-903.
– reference: 19. Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: an update. Eur Heart J 2014; 35: 1101-11.
– reference: 21. Cecchi F, Olivotto I, Gistri R, et al. Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. N Engl J Med 2023; 349: 1027-35.
– reference: 1. Kitaoka H, Tsutsui H, Kubo T, et al. JCS/JHFS 2018 Guideline on the Diagnosis and Treatment of Cardiomyopathies. Circ J 2021; 85: 1590-689.
– reference: 7. Kosuge H, Hachiya S, Fujita Y, et al. Potential of non-contrast stress T1 mapping for the assessment of myocardial injury in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2023; 25: 53.
– reference: 22. Taqueti VR, Solomon SD, Shah AM, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J 2018; 39: 840-9.
– reference: 6. Sobajima M, Nozawa T, Suzuki T, et al. Impact of myocardial perfusion abnormality on prognosis in patients with non-ischemic dilated cardiomyopathy. J Cardiol 2010; 56: 280-6.
– reference: 5. Mandawat A, Chattranukulchai P, Mandawat A, et al. Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes. JACC Cardiovasc Imaging 2021; 14: 1338-50.
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  doi: 10.1161/CIRCULATIONAHA.114.009625
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  doi: 10.1093/eurheartj/ehv727
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  doi: 10.1016/j.biopha.2023.115011
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  doi: 10.1016/j.jcmg.2018.10.032
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– ident: 21
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– ident: 16
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– ident: 5
  doi: 10.1016/j.jcmg.2020.11.006
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  doi: 10.1002/ehf2.12764
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  doi: 10.3389/fcvm.2023.1301509
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Snippet Hypokinetic non-dilated cardiomyopathy (HNDC), a preclinical state of dilated cardiomyopathy (DCM), is characterized by left ventricular (LV) dysfunction...
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SubjectTerms Aged
Arrhythmia
Brain natriuretic peptide
Cardiomyopathy
Cardiomyopathy, Dilated - complications
Cardiomyopathy, Dilated - diagnostic imaging
Cardiomyopathy, Dilated - mortality
Cardiomyopathy, Dilated - physiopathology
Congestive heart failure
Coronary Circulation - physiology
Coronary flow reserve
Coronary Vessels - diagnostic imaging
Coronary Vessels - physiopathology
Dilated cardiomyopathy
Female
Fibrosis
Gadolinium
Humans
Magnetic Resonance Imaging, Cine - methods
Male
Microvasculature
Middle Aged
Neuroimaging
Prognosis
Retrospective Studies
T1 mapping
Ventricle
Ventricular Dysfunction, Left - diagnostic imaging
Ventricular Dysfunction, Left - physiopathology
Ventricular remodeling
Title Coronary Microvascular Dysfunction and Adverse Outcomes in the Spectrum of Dilated Cardiomyopathy
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