takayasu arteritis - philippine heart association · takayasu arteritis: clinical classification...

Takayasu Arteritis: Patient Profile and Outcomes

Maria Teresa B. Abola, MD, FACC Philippine Heart Center

University of the Philippines Philippine General Hospital

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

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+onalJRheumDiseases,2014DeSouzaandCarvalho.JAutoimmunity,2014

Arteriovenousanastomosissurroundingpapillawithmicroaneurysms

Takayasu arteritis (TA): Pathology • Chronic granulomatous T cell- based inflammatory panarteritis of unknown etiology that primarily involves the aorta and its major branches. • 1940--first link between TA and arterial wall inflammation made when Kunio Ohta reported “panarteritis” in the aorta and its main branches

In+malthickening

Medialdegenera+on

• The outcome process of destruction and fibrotic repair depends on the dominant pathophysiologic process: destruction yields aneurysms while fibrosis causes stenosis.

AbolaandValdez,HistopathslideIMG_3521andIMG_3526,PathologyDept.,PhilHeartCenter,unpublished,2016DeSouzaandCarvalho.JAutoimmunity,2014www.studyblue.com

DeSouzaandCarvalho.JAutoimmunity,2014

Criterion Defini+on

Ageatdiseaseonset<40years

DevelopmentofsymptomsorfindingsrelatedtoTAatage<40yrs

Claudica+onofextremi+es

Developmentandworseningoffa+gueanddiscomfortinmusclesof>1extremitywhileinuse,espupperextremi+es

Decreasedbrachialarterypulse

Decreasedpulsa+onof1orbothbrachialarteries

BPdifference>10mmHg

Differenceof>10mmHginsystolicBPbetweenarms

Bruitoversubclavianarteriesoraorta

Bruitaudibleonausculta+onover1orbothsubclavianarteriesorabdominalaorta

Arteriogramabnormality

Arteriographicnarrowingorocclusionofen+reaorta,primarybranchesorlargearteriesinproximalupperorlowerextnotduetoatherosclerosisorFMD

Takayasu arteritis: 1990 ACR Classification •  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+sandRheuma+sm,August1990


Criterion Defini+on







BPdifference>10mmHg








LIMITATIONS: age restriction for

Disease onset (<40 years) and

TA patients with predominant aortic involvement


Criterion Defini+on







BPdifference>10mmHg








LIMITATIONS: age restriction for disease

onset (<40 years) and TA patients with

predominant aortic involvement

Diagnos+candClassifica+onCriteriainVasculi+sStudy(DCVAS)

Aninterna+onaleffortunderwaytodevelopasingleclassifica+onsystemandavalidatedsetofdiagnos+ccriteriaforsystemicvasculi+des

usingdata-drivenmethods.

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 2nd and 3rd decades of life

•  Predominantly female (82.9-97.0%) or ~ 10:1 female to male ratio

1Arend,et.al.,Arthri+sandRheuma+sm,Vol.33,No.8,August1990

Takayasu Arteritis: Philippine Multicenter Cohort*

Clinical Characteristic Distribution Demographics 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%

N=61

*Abola,Valdez,Afos,PhilippineHeartCenterandPhilippineGeneralHospital,unpublished2016

Comparison of Patient profile and Complications Characteristic Philippines1

N=61 2006 - 2015

Japan2

N=86 1990 - 2014

USA3

N=75 1992 - 2004

Age at onset (years) 33.5 36.4 26 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%

1Abola,Valdez,Afos,PhilippineHeartCenterandPhilippineGeneralHospital,unpublished20162Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016:19,pp87–94 3Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp 1000–1009

Takayasu Arteritis: Clinical Presentation Philippine and US Cohorts

Clinical Presentation Philippines1 %

USA2 %

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%

N=61

1Abola,Valdez,Afos,PhilippineHeartCenterandPhilippineGeneralHospital,unpublished20162Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp 1000–1009

Takayasu Arteritis: Carotid Duplex Scan Philippine Multicenter Cohort

LongitudinalviewoftheRightCommon(CCA)andInternalCaro+dArtery(ICA)

•  TA--long,smooth,homogeneousconcentricthickeningofthearterialwall

•  Atherosclero+cplaque--nonhomogeneous,irregular,ocencalcified

CCA

AbolaandValdez,PhilippineHeartCenterVascularLaboratory,unpublished,2016

Takayasu Arteritis: MR and CT Imaging Lecsubclaviana.Occlusionwith

collaterals

RightandLeccommonCaro+dstenoses

Right renal artery stenosis

Aortic aneurysm

Left Subclavian

Artery occlusion

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

Takayasu Arteritis: Distribution of Arterial Lesions USA1

JAPAN2,3

PHILIPPINES4KOREA3INDIA3

1Abola,Valdez,Afos,PhilippineHeartCenterandPhilippineGeneralHospital,unpublished20162Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016, 19:87–94; 3Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007, 56(3):1000–1009

Lesion Philippines1

Japan2

USA3

TypeofArterialDistribu+on V I - IIa I - IIa Top1 Subclavian

arterySubclavianartery

Aorta

Top2 Abdominalaorta Caro+dartery Subclavianartery

Top3 Descendingaorta

Aor+carch/ascendingaorta

Caro+dartery

Takayasu Arteritis: Distribution of Arterial Lesions USA1

JAPAN2,3

PHILIPPINES4KOREA3INDIA3

1Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007, 56(3):1000–1009; 2Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016, 19:87–94; 3Yajima M, et al. Jpn Circ J. 1994, 58:9 –14; 4Valdez and Abola, Present study, 2016; imaging.onlinejacc.org

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

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

Aydin, et.al. Rheumatology, 2015

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.IRAVASgroup,Rheumatology,2013

2pointsweight

2pointsweight

*1pointweight

*

*

*

*

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 2nd 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)

Ferfar Y, et al, Biotherapies in large vessel vasculitis, Autoimmun Rev (2016) Hiratzka, et.al. 2010 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

Medical Management of Takayasu Arteritis: Philippine Multicenter Cohort

Steroidsalone36%

Steroids+otherIST*43%

An+plateletalone7%

Others9%

Unknown5%

*IST–immunosuppressivetherapy(Azathioprine,Methotrexate,Tocilizumab,mycophenolate)

Abola, Valdez, Afos, Philippine Heart Center and Philippine General Hospital, unpublished 2016

Intervention for Takayasu Arteritis: Philippine Multicenter Cohort

MedicalManagement

alone72%

Endovascularplusmedicalmanagement

5%

Surgicalplusmedical

management31%

Surgeryalone2%

*

*Mostlyaor+csurgerywithperiopera+ve/30-daymortalityrate:4.9%**Endovasculartherapy–percutaneousrenalangioplasty

**


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.JofVascMed,2013DeSouzaandCarvalho.JAutoimmunity,2014

Takayasu Arteritis: Clinical Classification and Mortality Philippine Multicenter Cohort

*Complica+onsincludedaor+caneurysm,secondaryhypertension,aor+cregurgita+on,coronaryorcerebrovasculardisease

Group Clinical Features N (%) Death Group I Uncomplicated disease, with or

without pulmonary involvement 6 (9.8%) 0

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 deaths)

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








10-year survival rate = 82% 7 (11.5%) died within 5 years,

ALL from Group IIb or III.









Heart failure and arrhythmias were most common causes of death


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


Takayasu Arteritis: Outcomes of Intervention Philippine Multicenter Cohort

39%

4.90%

28.60%

28.60%

0%10%20%30%40%50%60%70%80%

Nonfataloutcomes

Death

EndovascularTreatmentSurgicalTreatmentMedicalTreatment


Comparison of Treatment and Outcomes Philippines1 2006 - 2015

Japan2

1990 - 2014 USA3

1992 - 2004 Cases, n 61 86 30* Steroids/IST (%) 75.4% 89.5% 93.3% Underwent PTA/Endovascular/ Surgical therapy, (%)

27.9% 37.2% 70%

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 Stroke

*Longitudinalcohort,n=30

1Abola, Valdez, Afos, Philippine Heart Center/UP Phil Gen Hosp ,unpublished 2016 2Yoshida, Watanabe, et.al., International Journal of Rheumatic Diseases, 2016:19,pp87–94 3Maksimowicz-McKinnon,Clark and Hoffman, Arthritis and Rheumatism, 2007:56(3), pp 1000–1009

IST = immunosuppressive therapy i.e. steroids, methotrexate, azathioprine, tocilizumab, mycophenolate

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.

•  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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