Takayasu Arteritis: Patient Profile and Outcomes
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1 Takayasu Arteritis: Patient Profile and Outcomes Maria Teresa B. Abola, MD, FACC Philippine Heart Center University of the Philippines Philippine General Hospital
2 Objectives Provide a brief review of the clinical presentation, diagnosis and treatment of Takayasu arteritis (TA) Present the patient profile and outcomes of Filipino patients with Takayasu arteritis Compare Philippine data with contemporary cohorts from other countries
3 Arteriovenous anastomosis surrounding papilla with microaneurysms Takayasu Arteritis: Incidence Rare disease 1905 first described by Dr. Mikito Takayasu, an ophthalmologist Annual incidence of TA = 0.4 to 2.6 cases per million Japan: 40 cases / million Terao, Interna+onal J Rheum Diseases, 2014 De Souza and Carvalho. J Autoimmunity, 2014
4 Takayasu arteritis (TA): Pathology In+mal thickening Medial degenera+on Chronic granulomatous T cellbased inflammatory panarteritis of unknown etiology that primarily involves the aorta and its major branches. The outcome process of destruction and fibrotic repair depends on the dominant pathophysiologic process:ta destruction first link between and yields while made fibrosis arterialaneurysms wall inflammation when causes stenosis. Kunio Ohta reported panarteritis in the aorta and its main branches Abola and Valdez, Histopath slide IMG_3521 and IMG_3526, Pathology Dept., Phil Heart Center, unpublished, 2016 De Souza and Carvalho. J Autoimmunity,
5 Criterion Age at disease onset < 40 years Claudica+on of extremi+es Decreased brachial artery pulse BP difference > 10 mm Hg Bruit over subclavian arteries or aorta Arteriogram abnormality Takayasu arteritis: 1990 ACR Classification Defini+on Development of symptoms or findings related to TA at age < 40 yrs Development and worsening of fa+gue and discomfort in muscles of > 1 extremity while in use, esp upper extremi+es Decreased pulsa+on of 1 or both brachial arteries Difference of > 10 mm Hg in systolic BP between arms Bruit audible on ausculta+on over 1 or both subclavian arteries or abdominal aorta Arteriographic narrowing or occlusion of en+re aorta, primary branches or large arteries in proximal upper or lower ext not due to atherosclerosis or FMD Diagnosis of TA made if at least 3 of 6 criteria are present. Presence of > 3 criteria SENSITIVITY of 90.5% and SPECIFICITY of 97.8% Arend, et.al., Arthri+s and Rheuma+sm, August 1990 De Souza and Carvalho. J Autoimmunity, 2014
6 Criterion Age at disease onset < 40 years Claudica+on of extremi+es Decreased brachial artery pulse BP difference > 10 mm Hg Bruit over subclavian arteries or aorta Arteriogram abnormality Takayasu arteritis: 1990 ACR Classification Defini+on Development of symptoms or findings related to TA at age < 40 yrs LIMITATIONS: age restriction for Disease onset (<40 years) and TA patients with predominant aortic involvement Development and worsening of fa+gue and discomfort in muscles of > 1 extremity while in use, esp upper extremi+es Decreased pulsa+on of 1 or both brachial arteries Difference of > 10 mm Hg in systolic BP between arms Bruit audible on ausculta+on over 1 or both subclavian arteries or abdominal aorta Arteriographic narrowing or occlusion of en+re aorta, primary branches or large arteries in proximal upper or lower ext not due to atherosclerosis or FMD Diagnosis of TA made if at least 3 of 6 criteria are present. Presence of > 3 criteria SENSITIVITY of 90.5% and SPECIFICITY of 97.8% Arend, et.al., Arthri+s and Rheuma+sm, August 1990 De Souza and Carvalho. J Autoimmunity, 2014
7 Takayasu arteritis: 1990 ACR Classification Criterion Defini+on Diagnosis of TA made if at least 3 of 6 criteria are Claudica+on of Development and worsening of fa+gue and LIMITATIONS: extremi+es discomfort in muscles of > 1 extremity while present. in use, esp upper Presence of > 3 criteria age restriction forextremi+es disease Decreased brachial Diagnos+c andofand Criteriaof 90.5% and Decreased pulsa+on 1Classifica+on or both brachial SENSITIVITY onset (<40 years) artery pulse arteries SPECIFICITY of 97.8% in Vasculi+s BP difference > 10 mm TA Difference of > 10with mm Hg in Study systolic BP (DCVAS) patients Age at disease onset < 40 years Development of symptoms or findings related to TA at age < 40 yrs between arms An interna+onal effort under way to predominant aortic involvement Bruit over subclavian Bruit audible on ausculta+on over 1 or both arteries or aorta subclavianclassifica+on arteries or abdominal aorta develop a single system and a validated Arteriogram Arteriographic narrowing or occlusion of en+re abnormality aorta, primary branches or large arteries in set of diagnos+c criteria for systemic vasculi+des proximal upper or lower ext not due to atherosclerosis or FMD using data-driven methods. Hg Arend, et.al., Arthri+s and Rheuma+sm, August 1990 De Souza and Carvalho. J Autoimmunity, 2014
8 Takayasu arteritis: Clinical Presentation Diagnosis often delayed for months to years due to nonspecific symptoms of fever, myalgias, arthralgia, weight loss, and anemia Usually diagnosed in young individuals in their 2 nd and 3 rd decades of life Predominantly female ( %) or ~ 10:1 female to male ratio 1 Arend, et.al., Arthri+s and Rheuma+sm, Vol. 33, No. 8, August 1990
9 Takayasu Arteritis: Philippine Multicenter Cohort* N = 61 Clinical Characteristic Demographics Distribution Age at onset (years) 33.5 Female (%) 77% Female to Male Ratio 3.4:1 Onset of Symptoms to diagnosis (years) 3.6 Age > 40 years at diagnosis (%) 29.5% Age > 40 years at onset of symptoms (%) 23% *Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016
10 Comparison of Patient profile and Complications Characteristic Philippines 1 N= Japan 2 N= USA 3 N= Age at onset (years) Age at onset > 40 23% 29% NA Female (%) 77.0% 91.9% 91.0% Elevated ESR (%) 59.0% N/A 73.0% Hypertension (%) 60.6% 39.5% 28.0% Visual disturbances (%) 22.9% 3.4% 12.0% Aortic/arterial aneurysm/dilatation (%) 55.7% 22.1% 11.0% Aortic regurgitation (%) 27.9% 48.8% 24.0% 1 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016:19, pp Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp
11 N = 61 Takayasu Arteritis: Clinical Presentation Philippine and US Cohorts Clinical Presentation Philippines 1 USA 2 % % Diminished pulse 73.8% 57% Differential BP 72.1% 53% Constitutional symptoms 55.7% N/A Claudication 49.2% 48% Presence of bruit 34.4% 53% Neurologic symptoms 32.8% 8% Heart failure symptoms 31.1% 7% Visual disturbances 9.8% 12% 1 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp
12 Takayasu Arteritis: Carotid Duplex Scan Philippine Multicenter Cohort CCA Longitudinal view of the Right Common (CCA) and Internal Caro+d Artery (ICA) Abola and Valdez, Philippine Heart Center Vascular Laboratory, unpublished, 2016 TA -- long, smooth, homogeneous concentric thickening of the arterial wall Atherosclero+c plaque -nonhomogeneous, irregular, ocen calcified
13 Takayasu Arteritis: MR and CT Imaging Right and Lec common Caro+d stenoses Lec subclavian a. Occlusion with collaterals Aortic aneurysm Right renal artery stenosis Abola, Valdez, CT scan image, Radiology laboratory, Philippine Heart Center, unpublished 2016 MRA images from Perrera, Mason and Wolfe, International J of Vasc Med; With permission from Dr. Wolfe Left Subclavian Artery occlusion
14 Takayasu Arteritis: Distribution of Arterial Lesions PHILIPPINES Lesion USA 1 Philippines 1 Japan 2 4 KOREA USA 3 3 JAPAN 2,3 INDIA 3 Type of Arterial Distribu+on V I - IIa I - IIa Top 1 Subclavian artery Subclavian artery Aorta Top 2 Abdominal aorta Caro+d artery Subclavian artery Top 3 Descending aorta Aor+c arch/ ascending aorta Caro+d artery 1 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016, 19:87 94; 3 Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007, 56(3):
15 Takayasu Arteritis: Distribution of Arterial Lesions USA 1 JAPAN 2,3 PHILIPPINES 4 KOREA 3 INDIA 3 1 Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007, 56(3): ; 2 Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016, 19:87 94; 3 Yajima M, et al. Jpn Circ J. 1994, 58:9 14; 4 Valdez and Abola, Present study, 2016; imaging.onlinejacc.org
16 Takayasu Arteritis: Disease Activity Patient symptoms constitutional symptoms and signs of arterial insufficiency Elevated acute phases reactants: high ESR, CRP and fibrinogen BUT no reliable serologic marker Pentraxin 3 (PTX 3) Imaging wall edema/thickening on MRA, PET but these may not be able to distinguish active vascular disease vs. damage Aydin, et.al. Rheumatology, 2015 PET scan and PET CT images demonstrating homogeneous linear uptake, suggestive of active disease. Perrera, Mason and Wolfe, International J of Vasc Med; With permission from Dr. Wolfe
17 * * * *1 point weight 2 points weight * 2 points weight Indian Takayasu Activity Score (ITAS2010) immediate usefulness in determining disease activity and standardizing clinical assessment of response to therapy in developing countries where cost limits repetitive imaging in usual practice. Misra, R., et.al. IRAVAS group, Rheumatology, 2013
18 Ferfar Y, et al, Biotherapies in large vessel vasculitis, Autoimmun Rev (2016) Hiratzka, et.al ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Thoracic Aortic Disease, Circulation. EULAR Recommendations for the Management of Large-vvessel Vasculitis, 2009 Takayasu arteritis: Medical Treatment AIM: control active inflammation and minimize arterial injury Glucorticoids (GC) still the mainstay of treatment (2010 guidelines) Relapses and GC dependence seen in > 2/3 of patients 46% - 84% will need 2 nd agent to achieve remission. anti-tnf α inhibitor (infliximab, adalimumab) anti-interleukin 6 receptor antibody (tocilizumab) anti-cd20 monoclonal antibody (rituximab) Only ongoing randomized trial: Abatacept (modulates signal required for T-cell activation)
19 Medical Management of Takayasu Arteritis: Philippine Multicenter Cohort An+platelet alone 7% Others 9% Unknown 5% Steroids alone 36% Steroids + other IST* 43% *IST immunosuppressive therapy (Azathioprine, Methotrexate, Tocilizumab, mycophenolate) Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016
20 * Surgical plus medical management 31% ** Endovascular plus medical management 5% Intervention for Takayasu Arteritis: Philippine Multicenter Cohort *Mostly aor+c surgery with periopera+ve/30-day mortality rate: 4.9% ** Endovascular therapy percutaneous renal angioplasty Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016 Surgery alone 2% Medical Management alone 72%
21 Takayasu arteritis: Outcomes mortality rate in TA ranged from 3 to 27% 5-year and 10-year survival rates were reported as 81-95% and 73-90%, respectively leading causes of death : congestive heart failure, acute MI, stroke and postoperative complications. Perrera, et.al., Int. J of Vasc Med, 2013 De Souza and Carvalho. J Autoimmunity, 2014
22 Takayasu Arteritis: Clinical Classification and Mortality Philippine Multicenter Cohort Group Clinical Features N (%) Death Group I Uncomplicated disease, with or 6 (9.8%) 0 without pulmonary involvement Group IIA Mild/Moderate single complication* 2 (3.3%) 0 Group IIB Severe single complication* 14 (22.9%) 2 (inhospital) Group III > 2 complications* 37 (60.6%) 5 (2 inhospital and 3 late *Complica+ons included aor+c aneurysm, secondary hypertension, aor+c regurgita+on, coronary or cerebrovascular disease Ishikawa K. Natural history and classification of occlusive thromboaortopathy (Takayasu s arteritis). Circulation 1978 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016 deaths)
23 Takayasu Arteritis: Clinical Classification and Mortality Philippine Multicenter Cohort Group 10-year Clinical survival Features rate = 82% N (%) Death Group I Uncomplicated disease, with or 6 (9.8%) 0 7 without (11.5%) pulmonary died involvement within 5 years, Group IIA Mild/Moderate ALL from Group single complication* IIb or III. 2 (3.3%) 0 Group IIB Severe single complication* 14 (22.9%) 2 (inhospital) Group III > 2 complications* 37 (60.6%) 5 (2 inhospital and 3 late *Complica+ons included aor+c aneurysm, secondary hypertension, aor+c regurgita+on, coronary or cerebrovascular disease Ishikawa K. Natural history and classification of occlusive thromboaortopathy (Takayasu s arteritis). Circulation 1978 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016 deaths)
24 Takayasu Arteritis: Clinical Classification and Mortality Philippine Multicenter Cohort Group Clinical Features N (%) Death Heart failure and arrhythmias Group I Uncomplicated disease, with or 6 (9.8%) 0 were most without common pulmonary involvement causes of death Group IIA Mild/Moderate single complication* 2 (3.3%) 0 Group IIB Severe single complication* 14 (22.9%) 2 (inhospital) Group III > 2 complications* 37 (60.6%) 5 (2 inhospital and 3 late *Complica+ons included aor+c aneurysm, secondary hypertension, aor+c regurgita+on, coronary or cerebrovascular disease Ishikawa K. Natural history and classification of occlusive thromboaortopathy (Takayasu s arteritis). Circulation 1978 Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016 deaths)
25 Takayasu arteritis: Outcomes Philippine Multicenter Cohort Outcomes* N (%) Persistence of symptoms 14 (22.9%) Vascular problems (Fistula formation, aneurysm formation, malperfusion syndrome, infected graft, graft occlusion or re-stenosis) 12 (19.7%) Neurologic complications (TIA/stroke, cerebral hemorrhage, paraplegia,spinal cord injury) 11 (18.0%) Re-intervention after the initial management strategy 10 (16.4%) Poor control of hypertension 7 (11.5%) Cardiac complications 7 (11.5%) Death 7(11.5%) Renal Insufficiency/Failure 5 (8.2%) * Long-term outcomes were associated with male sex and duration of treatment Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016
26 Takayasu Arteritis: Outcomes of Intervention Philippine Multicenter Cohort 80% 70% 60% 50% 40% 30% 20% 10% 0% 28.60% 39% Nonfatal outcomes 28.60% 4.90% Death Endovascular Treatment Surgical Treatment Medical Treatment Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016
27 Comparison of Treatment and Outcomes Philippines Japan USA Cases, n * Steroids/IST (%) 75.4% 89.5% 93.3% Underwent PTA/Endovascular/ 27.9% 37.2% 70% Surgical therapy, (%) Survival rate (%) 88.5% 95.3% 97.3% Mortality (%) 11.5% 4.7% 2.7% Causes of death Sudden cardiac death/arrhythmia/ heart failure Sudden Death IST = immunosuppressive therapy i.e. steroids, methotrexate, azathioprine, tocilizumab, mycophenolate 1 Abola, Valdez, Afos, Philippine Heart Center/UP Phil Gen Hosp,unpublished Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016:19, pp Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp Stroke * Longitudinal cohort, n = 30
28 Summary Takayasu arteritis is a rare disease that has global prevalence and highly variable presentation which may be related to ethnicity. Diagnosis is often delayed with patients presenting frequently already with complications. Progress in assessment of disease is indicated by which require more research and validation. Relapse and anatomic progression were seen in the majority of patients. Morbidity and mortality rate patterns vary depending on access to early diagnosis and treatment options.
29 Special thanks to Dr. Thessie Minelli Valdez (Vascular Medicine Division, Philippine Heart Center), Dr. Ivy Afos (Rheumatology Section, Philippine General Hospital), and Regina Isabel Abola
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