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Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy

  • Peter J. Psaltis
  • Angelo Carbone
  • Darryl P. Leong
  • Dennis H. Lau
  • Adam J. Nelson
  • Tim Kuchel
  • Troy Jantzen
  • Jim Manavis
  • Kerry Williams
  • Prashanthan Sanders
  • Stan Gronthos
  • Andrew C. W. Zannettino
  • Stephen G. WorthleyEmail author
Original Paper

Abstract

Cardiac fibrosis plays an important prognostic role in nonischemic cardiomyopathy (NICM), making it a potential therapeutic target. Although electromechanical mapping has been used to identify myocardial scar and facilitate intramyocardial intervention in the setting of ischemic heart disease, its application has not been described in NICM. We assessed the detection of myocardial fibrosis by endoventricular electromechanical mapping in an experimental model of NICM. The NOGA® XP system was used to perform left ventricular mapping in twelve sheep that had undergone intracoronary doxorubicin dosing to induce NICM and in six healthy control animals. Results for endocardial voltage and mechanical shortening were evaluated against myocardial fibrosis burden, as determined by delayed-enhancement cardiac magnetic resonance and quantitative histomorphometry. Doxorubicin treatment resulted in dilated cardiomyopathy with moderate-severe impairment of left ventricular ejection fraction. Late gadolinium uptake was present in 9/12 doxorubicin animals, while histological fibrosis was approximately doubled compared to controls and was distributed multisegmentally throughout the left ventricle. Cardiomyopathy was associated with widespread reductions in unipolar and bipolar voltage amplitude and endocardial shortening. Each parameter showed an inverse relationship with the burden of fibrosis. Moreover, unipolar voltage and linear local shortening ratio displayed moderate accuracy for identifying myocardial segments with delayed contrast enhancement or increased fibrosis content, with optimal discriminatory thresholds of 7.5 mV and 11.5%, respectively. In this model of NICM, electromechanical mapping shows potential for delineating segmental differences in fibrosis. Pending clinical evaluation, it may therefore have applicability for directing targeted intramyocardial interventions in nonischemic heart disease.

Keywords

Animal models Cardiac fibrosis Cardiac remodeling Mapping NOGA Nonischemic cardiomyopathy 

Notes

Acknowledgments

Personal funding was provided by the National Health and Medical Research Council of Australia (PJP, DHL, DPL), National Heart Foundation of Australia (PJP, DPL, PS), Kidney Health Australia (DHL), Royal Adelaide Hospital (PJP) and University of Adelaide (DHL). We thank Dr John Finnie, Adrian Hines, Melissa Gourlay and Jodie Dier (Veterinary Services Division, IMVS), Sofie Kogoj (Hanson Institute Centre for Neurological Diseases) and Dr. Michael Worthington (Department of Cardiothoracic Surgery, RAH) for their assistance during this study.

Disclosures

Dr. Jantzen is an employee of Biosense Webster, Johnson & Johnson Medical Pty Ltd, Australia.

Supplementary material

10554_2010_9657_MOESM1_ESM.doc (47 kb)
(DOC 47 kb)
10554_2010_9657_MOESM2_ESM.tif (884 kb)
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10554_2010_9657_MOESM3_ESM.tif (2 mb)
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Copyright information

© Springer Science+Business Media, B.V. 2010

Authors and Affiliations

  • Peter J. Psaltis
    • 1
    • 2
  • Angelo Carbone
    • 1
  • Darryl P. Leong
    • 1
  • Dennis H. Lau
    • 1
  • Adam J. Nelson
    • 1
  • Tim Kuchel
    • 3
  • Troy Jantzen
    • 4
  • Jim Manavis
    • 5
  • Kerry Williams
    • 1
  • Prashanthan Sanders
    • 1
  • Stan Gronthos
    • 2
  • Andrew C. W. Zannettino
    • 2
  • Stephen G. Worthley
    • 1
    Email author
  1. 1.Cardiovascular Research Centre, Royal Adelaide Hospital and Departments of Medicine and PhysiologyUniversity of AdelaideAdelaideAustralia
  2. 2.Bone and Cancer Laboratories, Division of Haematology, Institute of Medical and Veterinary Science & Centre for Stem Cell ResearchUniversity of AdelaideAdelaideAustralia
  3. 3.Veterinary Services DivisionInstitute of Medical and Veterinary ScienceAdelaideAustralia
  4. 4.Biosense-Webster, Johnson & Johnson Medical Pty LtdNorth RydeAustralia
  5. 5.Hanson Institute Centre for Neurological DiseasesInstitute of Medical and Veterinary ScienceAdelaideAustralia

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