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Imaging left ventricular remodeling: targeting the neurohumoral axis

Nature Clinical Practice Cardiovascular Medicine volume 5, pages S57–S62 (2008)Cite this article

Abstract

Left ventricular remodeling is a key determinant of the clinical course and outcome of systolic heart failure. The myocardial renin–angiotensin system (RAS) has been closely linked to the major maladaptive cellular and molecular changes that accompany left ventricular remodeling. Direct inhibition of various components of the RAS, such as the angiotensin-converting enzyme, angiotensin II type 1 receptor, and aldosterone, has resulted in favorable clinical responses in heart failure. Many questions, however, remain unanswered regarding the timing of initiation, optimum doses, need for simultaneous use of RAS inhibitors, and proper monitoring of RAS blockade. Additionally, significant variation has been noted in individual responses to RAS blockade as a result of genetic differences. Answering these questions requires direct access to the myocardial component of RAS, which is largely independent of its systemic component. Molecular imaging using radiotracers with high affinities for myocardial angiotensin-converting enzyme and angiotensin II type 1 receptors can provide direct access to tissue RAS and thus provide a better understanding of the pathophysiology of left ventricular remodeling in individual patients. This Article briefly reviews the potential for evaluating the tissue expression of angiotensin in heart failure by targeted RAS imaging.

Key Points

  • Left ventricular remodeling constitutes the disease process that eventually leads to symptomatic heart failure

  • The tissue renin–angiotensin system is closely linked to the myocardial cellular and molecular changes that accompany left ventricular remodeling

  • Wide variations are seen within individuals in the activity of the tissue renin–angiotensin system, mainly related to genetic factors

  • In clinical practice, the tissue renin–angiotensin system is not accessible and thus treatment of heart failure with inhibitors of this system remains largely empirical

  • Molecular imaging using radiotracers with high affinity for myocardial angiotensin converting enzyme and angiotensin-II type 1 receptor might provide an objective tool for individualizing the monitoring and treatment of left ventricular remodeling

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Figure 1: A schematic representation of the circulating and tissue renin–angiotensin system within the heart.
Figure 2: Favorable redistribution of absolute blood flow and associated increases in regional and global left ventricular function after 6 months of medical treatment with metoprolol in patients with ischemic cardiomyopathy.
Figure 3: The presence and distribution of angiotensin-converting-enzyme activity in relation to collagen replacement as assessed by Picrosirius red stain in human heart tissue removed from a cardiac transplant recipient with ischemic cardiomyopathy.
Figure 4: Micrographs showing immunolabeling of angiotensin-converting enzyme and angiotensin II type 1 receptor from normal and failing ovine hearts.

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Author information

Authors and Affiliations

  1. J Shirani is Professor of Medicine and Pathology, Director of the Fellowship Training Program and of Cardiovascular Noninvasive Research at the Geisinger Medical Center, Danville, PA, and,

    Jamshid Shirani

  2. Chief of the Nuclear Medicine Division, V Dilsizian is Professor of Medicine and Radiology, and Director of Cardiovascular Nuclear Medicine and PET Imaging at the University of Maryland School of Medicine, Baltimore, MD, USA.,

    Vasken Dilsizian

Authors
  1. Jamshid Shirani
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  2. Vasken Dilsizian
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Correspondence to Jamshid Shirani.

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The authors declare no competing financial interests.

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Shirani, J., Dilsizian, V. Imaging left ventricular remodeling: targeting the neurohumoral axis. Nat Rev Cardiol 5 (Suppl 2), S57–S62 (2008). https://doi.org/10.1038/ncpcardio1244

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