Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias

Rina Ariga, Elizabeth M. Tunnicliffe, Sanjay G. Manohar, Masliza Mahmod, Betty Raman, Stefan K. Piechnik, Jane M. Francis, Matthew D. Robson, Stefan Neubauer, Hugh Watkins

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia. Objectives: This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia. Methods: A total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T. Results: Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036). Conclusions: DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.

Original languageEnglish
Pages (from-to)2493-2502
Number of pages10
JournalJournal of the American College of Cardiology
Volume73
Issue number20
DOIs
Publication statusPublished - 28 May 2019
Externally publishedYes

Fingerprint

Hypertrophic Cardiomyopathy
Anisotropy
Cardiac Arrhythmias
Gadolinium
Fibrosis
Histology
Magnetic Resonance Spectroscopy
Diastole
Muscle Cells
Myocardium
Healthy Volunteers
Biomarkers

Keywords

  • diffusion tensor cardiac magnetic resonance imaging
  • disarray
  • fractional anisotropy
  • hypertrophic cardiomyopathy
  • risk stratification
  • sudden cardiac death
  • ventricular arrhythmia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Ariga, R., Tunnicliffe, E. M., Manohar, S. G., Mahmod, M., Raman, B., Piechnik, S. K., ... Watkins, H. (2019). Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias. Journal of the American College of Cardiology, 73(20), 2493-2502. https://doi.org/10.1016/j.jacc.2019.02.065

Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias. / Ariga, Rina; Tunnicliffe, Elizabeth M.; Manohar, Sanjay G.; Mahmod, Masliza; Raman, Betty; Piechnik, Stefan K.; Francis, Jane M.; Robson, Matthew D.; Neubauer, Stefan; Watkins, Hugh.

In: Journal of the American College of Cardiology, Vol. 73, No. 20, 28.05.2019, p. 2493-2502.

Research output: Contribution to journalArticle

Ariga, R, Tunnicliffe, EM, Manohar, SG, Mahmod, M, Raman, B, Piechnik, SK, Francis, JM, Robson, MD, Neubauer, S & Watkins, H 2019, 'Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias', Journal of the American College of Cardiology, vol. 73, no. 20, pp. 2493-2502. https://doi.org/10.1016/j.jacc.2019.02.065
Ariga, Rina ; Tunnicliffe, Elizabeth M. ; Manohar, Sanjay G. ; Mahmod, Masliza ; Raman, Betty ; Piechnik, Stefan K. ; Francis, Jane M. ; Robson, Matthew D. ; Neubauer, Stefan ; Watkins, Hugh. / Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias. In: Journal of the American College of Cardiology. 2019 ; Vol. 73, No. 20. pp. 2493-2502.
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abstract = "Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia. Objectives: This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia. Methods: A total of 50 HCM patients (47 ± 15 years of age, 77{\%} male) and 30 healthy control subjects (46 ± 16 years of age, 70{\%} male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T. Results: Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95{\%} confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036). Conclusions: DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.",
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author = "Rina Ariga and Tunnicliffe, {Elizabeth M.} and Manohar, {Sanjay G.} and Masliza Mahmod and Betty Raman and Piechnik, {Stefan K.} and Francis, {Jane M.} and Robson, {Matthew D.} and Stefan Neubauer and Hugh Watkins",
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T1 - Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias

AU - Ariga, Rina

AU - Tunnicliffe, Elizabeth M.

AU - Manohar, Sanjay G.

AU - Mahmod, Masliza

AU - Raman, Betty

AU - Piechnik, Stefan K.

AU - Francis, Jane M.

AU - Robson, Matthew D.

AU - Neubauer, Stefan

AU - Watkins, Hugh

PY - 2019/5/28

Y1 - 2019/5/28

N2 - Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia. Objectives: This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia. Methods: A total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T. Results: Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036). Conclusions: DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.

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KW - diffusion tensor cardiac magnetic resonance imaging

KW - disarray

KW - fractional anisotropy

KW - hypertrophic cardiomyopathy

KW - risk stratification

KW - sudden cardiac death

KW - ventricular arrhythmia

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