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Imaging of Inflammation and Calcification in Aortic Stenosis

  • Cardiac PET, CT, and MRI (S Achenbach, Section Editor)
  • Published:
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Abstract

Aortic stenosis is a common clinical condition that is set to increase in prevalence with an ageing population. However, reliable methods for predicting disease progression and effective medical therapies are lacking. Inflammation and calcification are believed to have a key role but until recently the relative contributions of these processes at the different stages of the disease process were unknown. Recent studies have suggested that combined positron emission tomography and computed tomography (PET/CT) is a feasible and reproducible method for measuring the degree of inflammation and calcification in the valves of patients with aortic stenosis. For the first time this provides us with a potential method of measuring disease activity, which might then allow prediction of progression and act as a surrogate endpoint in studies of novel therapies. In this review, we will examine the basis for PET/CT scanning and discuss the studies that have investigated its use in aortic stenosis. We will cover the work that is still required in order to validate this technique and how it might impact on future clinical research and practice. Finally, we will examine alternative imaging methods that might also provide insight in to the underlying pathogenesis of this important and common clinical condition.

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References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352:2389–97.

    Article  PubMed  CAS  Google Scholar 

  2. Chan KL, Teo K, Dumesnil JG, Ni A, Tam J. Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation. 2010;121:306–14.

    Article  PubMed  CAS  Google Scholar 

  3. Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343–56.

    Article  PubMed  Google Scholar 

  4. Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and myocardium. J Am Coll Cardiol. 2012;60:1854–63.

    Google Scholar 

  5. O'Brien KD, Reichenbach DD, Marcovina SM, Kuusisto J, Alpers CE, Otto CM. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of 'degenerative' valvular aortic stenosis. Arterioscler Thromb Vasc Biol. 1996;16:523–32.

    Article  PubMed  Google Scholar 

  6. Olsson M, Thyberg J, Nilsson J. Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves. Arterioscler Thromb Vasc Biol. 1999;19:1218–22.

    Article  PubMed  CAS  Google Scholar 

  7. Ghaisas NK, Foley JB, O'Briain DS, Crean P, Kelleher D, Walsh M. Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement. J Am Coll Cardiol. 2000;36:2257–62.

    Article  PubMed  CAS  Google Scholar 

  8. Jian B, Narula N, Li QY, Mohler III ER, Levy RJ. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75:457–65. discussion 465–6.

    Article  PubMed  Google Scholar 

  9. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol. 2007;171:1407–18.

    Article  PubMed  CAS  Google Scholar 

  10. Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol. 2006;47:1707–12.

    Article  PubMed  CAS  Google Scholar 

  11. Mohler 3rd ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001;103:1522–8.

    Article  PubMed  Google Scholar 

  12. Lin EC, Alavi A. PET and PET/CT. A clinical guide. New York; Stuttgart: Thieme; 2005.

  13. • Rudd JH, Narula J, Strauss HW, et al. Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? J Am Coll Cardiol. 2010;55:2527–35. Review article summarizing the literature investigating vascular 18F-FDG activity as a marker of plaque inflammation.

    Article  PubMed  Google Scholar 

  14. Rudd JH, Warburton EA, Fryer TD, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105:2708–11.

    Article  PubMed  CAS  Google Scholar 

  15. Tawakol A, Migrino RQ, Bashian GG, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–24.

    Article  PubMed  Google Scholar 

  16. Tahara N, Kai H, Ishibashi M, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol. 2006;48:1825–31.

    Article  PubMed  CAS  Google Scholar 

  17. Paulmier B, Duet M, Khayat R, et al. Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J Nucl Cardiol. 2008;15:209–17.

    Article  PubMed  Google Scholar 

  18. Rominger A, Saam T, Wolpers S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med. 2009;50:1611–20.

    Article  PubMed  Google Scholar 

  19. Muntendam P, McCall C, Sanz J, Falk E, Fuster V. The BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease--study design and objectives. Am Heart J. 2010;160:49–57 e1.

    Article  PubMed  Google Scholar 

  20. •• Dweck MR, Jones C, Joshi NV, et al. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012;125:76–86. This was the first prospective study to examine inflammation and calcification in aortic stenosis using PET/CT.

    Article  PubMed  CAS  Google Scholar 

  21. • Marincheva-Savcheva G, Subramanian S, Qadir S, et al. Imaging of the aortic valve using fluorodeoxyglucose positron emission tomography increased valvular fluorodeoxyglucose uptake in aortic stenosis. J Am Coll Cardiol. 2011;57:2507–15. A retrospective study of cancer patients demonstrating for the first time increased 18F-FDG activity in the valves of patients with aortic stenosis compared with those with normal valves.

    Article  PubMed  Google Scholar 

  22. Cheng VY, Slomka PJ, Ahlen M, Thomson LE, Waxman AD, Berman DS. Impact of carbohydrate restriction with and without fatty acid loading on myocardial (18)F-FDG uptake during PET: a randomized controlled trial. J Nucl Cardiol. 2010;17:286–91.

    Article  PubMed  Google Scholar 

  23. Wykrzykowska J, Lehman S, Williams G, et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med. 2009;50:563–8.

    Article  PubMed  Google Scholar 

  24. Blau M, Ganatra R, Bender MA. 18F-fluoride for bone imaging. Semin Nucl Med. 1972;2:31–7.

    Article  PubMed  CAS  Google Scholar 

  25. Foldager CB, Bendtsen M, Bunger C. PET scanning for evaluation of bone metabolism. Acta Orthop. 2009;80:737–8. author reply 738–9.

    Article  PubMed  Google Scholar 

  26. Hawkins RA, Choi Y, Huang SC, et al. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992;33:633–42.

    PubMed  CAS  Google Scholar 

  27. Messa C, Goodman WG, Hoh CK, et al. Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry. J Clin Endocrinol Metab. 1993;77:949–55.

    Article  PubMed  CAS  Google Scholar 

  28. Piert M, Zittel TT, Becker GA, et al. Assessment of porcine bone metabolism by dynamic. J Nucl Med. 2001;42:1091–100.

    PubMed  CAS  Google Scholar 

  29. Cook GJ, Blake GM, Marsden PK, Cronin B, Fogelman I. Quantification of skeletal kinetic indices in Paget’s disease using dynamic 18F-fluoride positron emission tomography. J Bone Miner Res. 2002;17:854–9.

    Article  PubMed  CAS  Google Scholar 

  30. Frost ML, Fogelman I, Blake GM, Marsden PK, Cook Jr G. Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis. J Bone Miner Res. 2004;19:1797–804.

    Article  PubMed  CAS  Google Scholar 

  31. Derlin T, Richter U, Bannas P, et al. Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. J Nucl Med. 2010;51:862–5.

    Article  PubMed  Google Scholar 

  32. Derlin T, Wisotzki C, Richter U, et al. In vivo imaging of mineral deposition in carotid plaque using 18F-sodium fluoride PET/CT: correlation with atherogenic risk factors. J Nucl Med. 2011;52:362–8.

    Article  PubMed  Google Scholar 

  33. Dweck MR, Chow MW, Joshi NV, et al. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012;59:1539–48.

    Article  PubMed  CAS  Google Scholar 

  34. Houslay ES, Cowell SJ, Prescott RJ, et al. Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial. Heart. 2006;92:1207–12.

    Article  PubMed  CAS  Google Scholar 

  35. Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol. 2005;46:166–72.

    Article  PubMed  CAS  Google Scholar 

  36. Raggi P, Davidson M, Callister TQ, et al. Aggressive vs moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: beyond endorsed lipid lowering with EBT scanning (BELLES). Circulation. 2005;112:563–71.

    Article  PubMed  CAS  Google Scholar 

  37. • Folco EJ SY, Rocha VZ, Christen T, Shvartz E, Sukhova GK, Di Carli MF, et al. Hypoxia but not inflammation augments glucose uptake in human macrophages. J Am Coll Cardiol. 2011;58:603–14. In vitro study examining the mechanisms underlying 18-FDG activity in the vasculature, which suggested that hypoxia increases macrophage uptake.

    Article  PubMed  Google Scholar 

  38. Bird JL, Izquierdo-Garcia D, Davies JR, et al. Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis. Atherosclerosis. 2010;210:388–91.

    Article  PubMed  CAS  Google Scholar 

  39. Kenny LM, Coombes RC, Oulie I, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med. 2008;49:879–86.

    Article  PubMed  Google Scholar 

  40. Verjans J, Wolters S, Laufer W, et al. Early molecular imaging of interstitial changes in patients after myocardial infarction: comparison with delayed contrast-enhanced magnetic resonance imaging. J Nucl Cardiol. 2010;17:1065–72.

    Article  PubMed  Google Scholar 

  41. Furumoto S, Takashima K, Kubota K, Ido T, Iwata R, Fukuda H. Tumor detection using 18F-labeled matrix metalloproteinase-2 inhibitor. Nucl Med Biol. 2003;30:119–25.

    Article  PubMed  CAS  Google Scholar 

  42. Toutouzas K, Drakopoulou M, Synetos A, et al. In vivo aortic valve thermal heterogeneity in patients with nonrheumatic aortic valve stenosis the: first in vivo experience in humans. J Am Coll Cardiol. 2008;52:758–63.

    Article  PubMed  Google Scholar 

  43. Richards JM, Semple SI, MacGillivray TJ, et al. Abdominal aortic aneurysm growth predicted by uptake of ultrasmall superparamagnetic particles of iron oxide: a pilot study. Circ Cardiovasc Imaging. 2011;4:274–81.

    Article  PubMed  Google Scholar 

  44. New SE, Aikawa E. Molecular imaging insights into early inflammatory stages of arterial and aortic valve calcification. Circ Res. 2011;108:1381–91.

    Article  PubMed  CAS  Google Scholar 

  45. Yoo H, Kim JW, Shishkov M, et al. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med. 2011;17:1680–4.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work and MRD were supported by a fellowship grant from the British Heart Foundation (FS/10/026). N.V.J. is supported by Chief Scientist Office (ETM/160). The work of J.H.F.R. is supported in part by the NIHR Cambridge Biomedical Research Centre. DEN is supported by the British Heart Foundation (CH/09/002).

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Centre for Cardiovascular Science, University of Edinburgh, Little France Crescent, Edinburgh, UK

    Marc R. Dweck, Nikhil V. Joshi & David E. Newby

  2. Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK

    Marc R. Dweck, Nikhil V. Joshi & David E. Newby

  3. Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK

    James H. F. Rudd

Authors
  1. Marc R. Dweck
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  2. Nikhil V. Joshi
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  3. James H. F. Rudd
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  4. David E. Newby
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Corresponding author

Correspondence to Marc R. Dweck.

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This article is part of the Topical Collection on Cardiac PET, CT, and MRI

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Dweck, M.R., Joshi, N.V., Rudd, J.H.F. et al. Imaging of Inflammation and Calcification in Aortic Stenosis. Curr Cardiol Rep 15, 320 (2013). https://doi.org/10.1007/s11886-012-0320-8

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  • DOI: https://doi.org/10.1007/s11886-012-0320-8

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