Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis
The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matche...
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| Published in | Circulation (New York, N.Y.) Vol. 125; no. 1; pp. 76 - 86 |
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| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
Lippincott Williams & Wilkins
03.01.2012
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.
Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001).
Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.
http://www.clinicaltrials.gov. Unique identifier: NCT01358513. |
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| AbstractList | The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.
Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001).
Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.
http://www.clinicaltrials.gov. Unique identifier: NCT01358513. The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.BACKGROUNDThe pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown.Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001).METHODS AND RESULTSPatients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001).Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.CONCLUSIONSPositron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF.http://www.clinicaltrials.gov. Unique identifier: NCT01358513.CLINICAL TRIAL REGISTRATIONhttp://www.clinicaltrials.gov. Unique identifier: NCT01358513. |
| Author | van Beek, Edwin J.R. Dweck, Marc Richard Wallace, William A. Salter, Donald M. Jones, Charlotte Boon, Nicholas A. Fletcher, Alison M. Newby, David E. Clark, John C. Richardson, Hamish Rudd, James H.F. Marsden, Mark Pessotto, Renzo McKillop, Graham Joshi, Nikhil V. White, Audrey |
| Author_xml | – sequence: 1 givenname: Marc Richard surname: Dweck fullname: Dweck, Marc Richard organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 2 givenname: Charlotte surname: Jones fullname: Jones, Charlotte organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 3 givenname: Nikhil V. surname: Joshi fullname: Joshi, Nikhil V. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 4 givenname: Alison M. surname: Fletcher fullname: Fletcher, Alison M. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 5 givenname: Hamish surname: Richardson fullname: Richardson, Hamish organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 6 givenname: Audrey surname: White fullname: White, Audrey organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 7 givenname: Mark surname: Marsden fullname: Marsden, Mark organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 8 givenname: Renzo surname: Pessotto fullname: Pessotto, Renzo organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 9 givenname: John C. surname: Clark fullname: Clark, John C. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 10 givenname: William A. surname: Wallace fullname: Wallace, William A. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 11 givenname: Donald M. surname: Salter fullname: Salter, Donald M. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 12 givenname: Graham surname: McKillop fullname: McKillop, Graham organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 13 givenname: Edwin J.R. surname: van Beek fullname: van Beek, Edwin J.R. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 14 givenname: Nicholas A. surname: Boon fullname: Boon, Nicholas A. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 15 givenname: James H.F. surname: Rudd fullname: Rudd, James H.F. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom – sequence: 16 givenname: David E. surname: Newby fullname: Newby, David E. organization: From the Centre for Cardiovascular Science (M.R.D., C.J., N.V.J., A.W., M.M., R.P., W.A.W., D.M.S., N.A.B., D.E.N.), Clinical Research Imaging Centre (M.R.D., C.J., N.V.J., A.M.F., H.R., J.C.C., G.M., E.J.R.v.B., D.E.N.), and Division of Pathology (W.A.W., D.M.S.), University of Edinburgh, Edinburgh; and Division of Cardiovascular Medicine, University of Cambridge, Cambridge (J.H.F.R.), United Kingdom |
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| References | e_1_3_4_3_2 e_1_3_4_2_2 Shankar LK (e_1_3_4_17_2) 2006; 47 e_1_3_4_9_2 e_1_3_4_8_2 Kaden JJ (e_1_3_4_27_2) 2004; 13 e_1_3_4_7_2 e_1_3_4_6_2 e_1_3_4_5_2 e_1_3_4_4_2 Weber WA (e_1_3_4_20_2) 1999; 40 e_1_3_4_22_2 e_1_3_4_23_2 e_1_3_4_21_2 e_1_3_4_26_2 e_1_3_4_24_2 e_1_3_4_28_2 e_1_3_4_29_2 e_1_3_4_30_2 e_1_3_4_11_2 e_1_3_4_34_2 e_1_3_4_12_2 e_1_3_4_33_2 e_1_3_4_32_2 e_1_3_4_10_2 e_1_3_4_31_2 e_1_3_4_15_2 e_1_3_4_16_2 e_1_3_4_13_2 e_1_3_4_14_2 e_1_3_4_19_2 Mohler ER (e_1_3_4_25_2) 1999; 8 e_1_3_4_18_2 22090164 - Circulation. 2012 Jan 3;125(1):9-11. doi: 10.1161/CIRCULATIONAHA.111.073452. |
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| SubjectTerms | Aged Aged, 80 and over Aortic Valve - diagnostic imaging Aortic Valve - pathology Aortic Valve Stenosis - diagnostic imaging Aortic Valve Stenosis - epidemiology Aortic Valve Stenosis - pathology Biological and medical sciences Blood and lymphatic vessels Calcinosis - diagnostic imaging Calcinosis - epidemiology Calcinosis - pathology Cardiology. Vascular system Cardiomyopathies - diagnostic imaging Cardiomyopathies - epidemiology Cardiomyopathies - pathology Cohort Studies Diseases of the aorta Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Female Fluorodeoxyglucose F18 Humans Inflammation - diagnosis Inflammation - diagnostic imaging Inflammation - epidemiology Male Medical sciences Positron-Emission Tomography - methods Prospective Studies Tomography, X-Ray Computed - methods |
| Title | Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis |
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