Relationship Between Cardiac Fibroblast Activation Protein Activity by Positron Emission Tomography and Cardiovascular Disease

被引:110
作者
Heckmann, Markus B. [1 ,3 ]
Reinhardt, Finn [1 ,3 ]
Finke, Daniel [1 ,3 ]
Katus, Hugo A. [1 ,3 ]
Haberkorn, Uwe [2 ,4 ,5 ]
Leuschner, Florian [1 ,3 ]
Lehmann, Lorenz H. [1 ,3 ,6 ]
机构
[1] Heidelberg Univ Hosp, Dept Cardiol Angiol & Pneumol, Heidelberg, Germany
[2] Heidelberg Univ Hosp, Dept Nucl Med, Heidelberg, Germany
[3] German Ctr Cardiovasc Res DZHK, Heidelberg Mannheim Partner Site, Heidelberg, Germany
[4] DKFZ, Clin Cooperat Unit Nucl Med, Heidelberg, Germany
[5] German Ctr Lung Res DZL, Translat Lung Res Ctr Heidelberg TLRC, Heidelberg, Germany
[6] German Canc Res Ctr, Heidelberg, Germany
关键词
diabetes mellitus; fibroblast; myocardial infarction; risk factors; tomography; ALPHA;
D O I
10.1161/CIRCIMAGING.120.010628
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: FAP (fibroblast activation protein) plays an important role in cardiac wound healing and remodeling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI (FAP inhibitor) tracers have recently been used to study cardiac remodeling following myocardial infarction in small-animal models. The aim of the study was to evaluate the activity of FAP via FAPI-positron emission tomography-computed tomography scans in human hearts. Methods: FAPI-positron emission tomography-computed tomography scans of 229 patients of 2 consecutive cohorts (modeling cohort: n=185; confirmatory cohort: n=44) suffering from metastasized cancer were analyzed applying the American Heart Association 17-segment model of the left ventricle. Logistic regression models were created using data from the modeling cohort. Multivariate regression models were established using Akaike information criterion in a step-down approach. Results: Fourteen percent of patients had preexisting coronary artery disease (n=31), 33% arterial hypertension (n=75), and 12% diabetes mellitus type II (n=28). Forty-three percent had been treated with platin derivatives (n=100), 14% with anthracyclines (n=32), and 10% had a history of prior radiation to the chest (n=23). High left ventricular FAPI signals correlated with the presence of cardiovascular risk factors (odds ratio [OR], 4.3,P=0.0029), a focal myocardial signal pattern (OR, 3.9,P=0.0068), diabetes mellitus type II (OR, 4.1,P=0.046), and beta-blocker use (OR, 3.8,P=0.049) in univariate regression models. In a multivariate analysis, increased signal intensity was significantly higher in patients with cardiovascular risk factors (overweight [OR, 2.6,P=0.023], diabetes mellitus type II [OR, 2.9,P=0.041], certain chemotherapies [platinum derivatives; OR, 3.0,P=0.034], and a history of radiation to the chest [OR, 3.5,P=0.024]). A focal enrichment pattern was more frequently observed in patients with known cardiovascular risk factors (P<0.0001). Conclusions: FAPI-positron emission tomography-computed tomography scans represent a new imaging modality to investigate cardiac FAP. High signal intensities correlate with cardiovascular risk factors and metabolic disease.
引用
收藏
页数:9
相关论文
共 27 条
[1]   Targeting cardiac fibrosis with engineered T cells [J].
Aghajanian, Haig ;
Kimura, Toru ;
Rurik, Joel G. ;
Hancock, Aidan S. ;
Leibowitz, Michael S. ;
Li, Li ;
Scholler, John ;
Monslow, James ;
Lo, Albert ;
Han, Wei ;
Wang, Tao ;
Bedi, Kenneth ;
Morley, Michael P. ;
Saldana, Ricardo A. Linares ;
Bolar, Nikhita A. ;
McDaid, Kendra ;
Assenmacher, Charles-Antoine ;
Smith, Cheryl L. ;
Wirth, Dagmar ;
June, Carl H. ;
Margulies, Kenneth B. ;
Jain, Rajan ;
Pure, Ellen ;
Albelda, Steven M. ;
Epstein, Jonathan A. .
NATURE, 2019, 573 (7774) :430-+
[2]   Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses [J].
Alonso-Merino, Elvira ;
Martin Orozco, Rosa ;
Ruiz-Llorente, Lidia ;
Martinez-Iglesias, Olaia A. ;
Pedro Velasco-Martin, Juan ;
Montero-Pedrazuela, Ana ;
Fanjul-Rodriguez, Luisa ;
Contreras-Jurado, Constanza ;
Regadera, Javier ;
Aranda, Ana .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (24) :E3451-E3460
[3]   Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata [J].
Brokopp, Chad E. ;
Schoenauer, Roman ;
Richards, Peter ;
Bauer, Stefan ;
Lohmann, Christine ;
Emmert, Maximilian Y. ;
Weber, Benedikt ;
Winnik, Stephan ;
Aikawa, Elena ;
Graves, Kirk ;
Genoni, Michele ;
Vogt, Peter ;
Luescher, Thomas F. ;
Renner, Christoph ;
Hoerstrup, Simon P. ;
Matter, Christian M. .
EUROPEAN HEART JOURNAL, 2011, 32 (21) :2713-2722
[4]   Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities [J].
Cavalera, Michele ;
Wang, Junhong ;
Frangogiannis, Nikolaos G. .
TRANSLATIONAL RESEARCH, 2014, 164 (04) :323-335
[5]   Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart - A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association [J].
Cerqueira, MD ;
Weissman, NJ ;
Dilsizian, V ;
Jacobs, AK ;
Kaul, S ;
Laskey, WK ;
Pennell, DJ ;
Rumberger, JA ;
Ryan, T ;
Verani, MS .
CIRCULATION, 2002, 105 (04) :539-542
[6]   Molecular imaging of cardiac remodelling after myocardial infarction [J].
Curley, Daniel ;
Plaza, Begona Lavin ;
Shah, Ajay M. ;
Botnar, Rene M. .
BASIC RESEARCH IN CARDIOLOGY, 2018, 113 (02)
[7]   68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers [J].
Giesel, Frederik L. ;
Kratochwil, Clemens ;
Lindner, Thomas ;
Marschalek, Manfred M. ;
Loktev, Anastasia ;
Lehnert, Wencke ;
Debus, Juergen ;
Jaeger, Dirk ;
Flechsig, Paul ;
Altmann, Annette ;
Mier, Walter ;
Haberkorn, Uwe .
JOURNAL OF NUCLEAR MEDICINE, 2019, 60 (03) :386-392
[8]   Post hoc ergo propter hoc [J].
Grouse, Lawrence .
JOURNAL OF THORACIC DISEASE, 2016, 8 (07) :E511-E512
[9]   Evidence for a cardiac metabolic switch in patients with Hodgkin's lymphoma [J].
Heckmann, Markus B. ;
Totakhel, Belal ;
Finke, Daniel ;
Anker, Markus S. ;
Mueller-Tidow, Carsten ;
Haberkorn, Uwe ;
Katus, Hugo A. ;
Lehmann, Lorenz H. .
ESC HEART FAILURE, 2019, 6 (04) :824-829
[10]   Targeted Ablation of Periostin-Expressing Activated Fibroblasts Prevents Adverse Cardiac Remodeling in Mice [J].
Kaur, Harmandeep ;
Takefuji, Mikito ;
Ngai, C. Y. ;
Carvalho, Jorge ;
Bayer, Julia ;
Wietelmann, Astrid ;
Poetsch, Ansgar ;
Hoelper, Soraya ;
Conway, Simon J. ;
Moellmann, Helge ;
Looso, Mario ;
Troidl, Christian ;
Offermanns, Stefan ;
Wettschureck, Nina .
CIRCULATION RESEARCH, 2016, 118 (12) :1906-+