Jitendra Sharma¹, Tarun Madan^2a, Dinesh Joshib^2a, Riyaz Charaniya^2a*, Pratik Raval^2a, Vishal Sharma^2a, Himani Upadhyaya^2b, Krutika Patel^2b

¹Accord Hospital, Bhuj. Gujarat, 370001, India

^2aDepartment of cardiology and ^2bDepartment of Research, U. N. Mehta Institute of Cardiology and Research Centre (UNMICRC), Civil Hospital Campus, Asarwa, Ahmedabad-380016, Gujarat, India

Abstract

Objective: Takayasu arteritis is a rare, chronic, inflammatory disease that primarily affects the aorta and its major branches. It mainly affects young females, and it can cause significant morbidity and mortality if untreated. The aim of this study was to evaluate the demographic profile, clinical manifestations, diagnostic features, angiographic findings in patients with aortoarteritis (Takayasu arteritis).

Methods: We enrolled prospectively 116 patients with Takayasu arteritis who came to Cardiology OPD at tertiary cardiac care hospital. We looked for constitutional symptoms, heart-related symptoms, systemic hypertension, neurological symptoms and upper & lower limb fatigue and claudication. We evaluated our patients using different diagnostic criteria: clinical, ACR criteria and Indian Takayasu Activity score. We also studied the angiographic profile and lesion characteristics in these patients, based on peripheral and coronary angiograms.

Results: We studied patients consisted of 14 male patients (12.1%) and 102 female patients (87.9%). Type V Takayasu arteritis was most common type (36.2%). Fatigue (60%) was most common cardinal symptom followed by myalgia (30%) and arthralgia (10%). About 43% of patients had neurological symptoms. Systemic hypertension (67%) was the most common manifestation of renal involvement. 110(95%) of the patients met clinical criteria and 105(91%) patients had American College of Rheumatology (ACR) score ≥3. Angiographic evidence of left renal artery stenosis was more (20%) than right renal artery stenosis (15%). bilateral renal artery involvement was found in 29% of patients.

Conclusion: Type V Takayasu arteritis was most common type (36.2%) of total study population. Hypertension and subclavian artery involvement both were seen in 2/3rd of population. Angiographic evidence of right and left renal artery stenosis was seen in 15% and 20% respectively, while bilateral renal artery involvement was found in 29% of patients.

Take home message: Takayasu arteritis rarely involves the coronary arteries. Angiographic evidence of right and left renal artery stenosis was observed in 15% and 20% of patients, respectively, with bilateral renal artery involvement found in 29% of patients.

Key words: Clinical presentation, aorta, renal artery, coronary artery,  Takayasu aortoarteritis

Introduction

Aortoarteritis (Takayasu arteritis) is a condition that affects people of all races and has an estimated incidence of 1.2-2.6/million per year in the Western population. It is more common in Southeast Asia, Central and South America, and Africa (1). Around 10% of Takayasu arteritis patients have no symptoms (2). Clinical manifestations of Takayasu arteritis are primarily determined by disease stages, which is divided into two phases, the first of which is pre-pulseless and the second of which is occlusive (3, 4)

The pulseless disease chronic inflammatory arteritis, mainly affects the coronary, carotid, pulmonary, and renal arteries in addition to aorta and its major branches (5, 6).  

Takayasu's arteritis causes arterial media to be destroyed, which can occasionally result in aneurysm formation. It also causes increasing wall fibrosis and lumen constriction (6).

Many biomarkers had been investigated to assess disease activity of Takaysu aortoarteritis; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are the most commonly used biomarkers for the assessment of disease activity of Takaysu aortoarteritis.

The aim of this study was to evaluate the demographic profile, clinical manifestations, diagnostic features, angiographic findings in patients with aortoarteritis (Takayasu arteritis).

Methods

Study population and design

Prospective observational study was performed in 116 patients with Takayasu Arteritis satisfying the 1990 American College of Rheumatology (ACR), Ishikawa's, or Sharma's criteria were recruited from cardiology outpatient department at tertiary cardiac care hospital from September 2018 to February 2021. The study has been approved by the institutional ethics committee (UNMICRC/CARDIO/2018/15).Informed consent was obtained from all individual participants the manuscript.

Definitions

We studied 116 patients’ data related to clinical presentation, disease extent (DEI.Tak score), activity (Indian Takayasu arteritis clinical activity score), angiography and treatment variables were collected for all patients. ACR and Ishikawa's Criteria for Takayasu's Arteritis (Modified According to Sharma et al.)( 10, 11) criteria include limb claudication, pulselessness or pulse differences in limbs, an unobtainable or significant blood pressure difference (>10 mmHg systolic blood pressure difference in limb), fever, neck pain, transient amaurosis, blurred vision, syncope, dyspnea or palpitations.

The American College of Rheumatology (ACR) has created Takayasu arteritis categorization criteria (3 of 6 are required) (10). When three or more criteria are present, the sensitivity of criteria in diagnosis of Takayasu arteritis is 90.5% and the specificity -  97.8%. The following are the criteria:

1. Age of 40 or less at disease beginning

2. Extensive claudication of the extremities

3. A reduction in the pulse of one or both brachial arteries

4. A difference in systolic blood pressure of at least 10 mm Hg between arms

5. A bruising of one or both of the subclavian arteries or the abdominal aorta

6. Arteriographic constriction or occlusion of the entire aorta, its principal branches, or big arteries in the upper or lower limbs caused by something other than arteriosclerosis, fibromuscular dysplasia, or other causes.

Data Collection

Based on peripheral and coronary angiograms, we collected data on the angiographic profile and lesion characteristics in these patients. We investigated these individuals' demographic, clinical, diagnostic, and angiographic profiles. We examined for constitutional symptoms, heart-related symptoms, systemic hypertension, neurological symptoms, and exhaustion and claudication in the upper and lower limbs.

Statistical analysis

 Statistical analysis was performed using  SPSS 26.0 software (IBM, Inc., Chicago, IL, USA). The categorical variables are expressed as number- percentages, and the continuous variables are expressed as the mean (standard deviation).

Results

Our study patients consisted of 14 male patients (12.1%) and 102 female patients (87.9%), with female to male ratio of 7.28:1. Demographic and symptoms of total population are mentioned in table 1. The mean age of total population was 30.16 (11) years with mean body mass index -  22 (5) Kg/m². Most common age of presentation was in age group 21 to 30 years (49%) followed by age group of 31 to 40 years (41%). The cardinal symptoms were - myalgia/arthralgia, neurological and mesenteric. Fatigue (60%) was most common cardinal symptom followed by myalgia (30%) and arthralgia (10%). Out of 116 patients 35(31%) had all cardinal symptoms. Cardiovascular system  (CVS) (manifestations were seen in almost 52% of cases with exertional dyspnea being the most common symptom. Orthopnea and paroxysmal nocturnal dyspnea (PND) were least common symptoms (both less than 3%). About 43% of patients had neurological symptoms and of which giddiness was most common (39%), followed by syncope (21%), neck pain (16%) and stroke (12%), seizure and blurred vision (5%), TIA (2%) were least common symptoms.  Mesenteric manifestations were sees less commonly, around 15% in all. Most common symptoms of this were weight loss (19%), followed by anorexia (16%) and postprandial abdominal pain (11%). Systemic hypertension (67%) was seen as the most common manifestation of renal involvement. Though, renal failure was rarely noticed (3% of patients). Upper limb claudication was seen in about 40% of the cases, with bilateral upper limb claudication in quarter of the patients. Lower limb claudication was seen in about 30% of the cases.  Overall, 41% of the patients had miscellaneous complaints with headache as the most common complaint. About 1/5th of the patients had past history of tuberculosis (11%). Patients had increased sedimentation rate and C-reactive protein.

Clinical diagnostic criteria are mentioned in Table 2. Type V Takayasu arteritis was most common type in the present study and comprised 36.2% of total study population followed by type I (22.4%) and type II B (13.8%), type III (12.1%), type IV (8.6%) and type II A (6.9%). One hundred ten (95%) of the patients met clinical criteria and 105(91%) patients had ACR score ≥3. All of the study patients met at least one of the criteria (either clinical or ACR). At first visit 95% of patients showed ITAS score ≥ 3.

Angiographic profile of total population is mentioned in Table 3. The lesions of coronary and pulmonary artery were less commonly seen, in less than 20% of cases each. Angiographic evidence of right and left renal artery stenosis was seen in 15% and 20% respectively, while bilateral renal artery involvement was found in 29% of patients.

Discussion

The mean age of presentation of Takayasu arteritis in the present study was 30.16 (11) years. In the study of 88 patients by Subramanyam et al (12) from  India, the mean age at symptom onset was 24 (9) years and mean age at diagnosis was 28 (10) years. In a large observational study done in Japan by Watanabe et al. (13) the median age at onset was 35 years, which was significantly higher in male patients (median, 43.5 years) than in female patients (median, 34 years; p<0.001). Previous studies have shown predilection for females though with a wide geographical variation. In the present study there were 14 male patients (12.1%) and 102 female patients (87.9%), with female: male ratio of 7.28:1. Panja et al.  (14) reported  female to male ratio as  6.4:1.14.

Type V Takayasu arteritis was most common type in the present study and comprised 37% of total study population followed by type I, type II, type III and type IV.  However , there is a wide variation in the frequency of occurrence of types of arteritis. The genetic, regional and environmental factors may have a play in this varied spectrum.

Agarwal et al (15) reported type III (53%) is most common among north Indian patients and in a large series data of Panja et al showed type IV (36%) is most common type of Takayasu arteritis in patients belonging to Eastern India and Bangladesh (14).

 Almost all patients (97%) had one or other cardinal symptoms. Fatigue was most common cardinal symptom  in our patients followed by myalgia and weight loss. Of all the patients, 31% had all cardinal symptoms listed in the study. These findings correlate with other studies, in which symptoms like fever, night sweat, malaise, weight loss, arthralgia, myalgia and mild anemia were common symptoms, usually associated with the early or pre-pulseless phase (16).

CVS system manifestations were seen in almost 60% of cases with exertional dyspnea being the most common symptom. Orthopnea and paroxysmal nocturnal dyspnea were least common symptoms (both less than 3%) (17). Hoffman in his study found CVS symptoms in 38% of cases, most common being dyspnea followed by angina, palpitations (< 10%) and cardiac failure (<5%) (18).

About, 43% of our patients had neurological symptoms and of which giddiness was most common, followed by blurred vision and syncope. About 12% of our patients had a history of stroke. Hoffman found CNS symptoms in 57% of cases, most common being giddiness (18). Kim et al. (19) found headache in 50-70% of cases, vertigo and convulsions in 0-20% and stroke in 5-9% of cases.

According to Morwaki et al. (20)Japanese patients have higher rate of neurological complications, because of more frequent aortic arch involvement as compared to Indian patients in whom abdominal aorta and renal arteries are more commonly involved (21).

Mesenteric symptoms were less common, accounting for around 15% of all cases. Weight loss was the most prevalent, followed by anorexia and postprandial stomach pain. The most common sign of renal involvement was systemic hypertension (67%). Although renal failure was uncommon (seen in less than 3% of individuals). Approximately 60% of our study participants exhibited systemic hypertension, which was comparable to earlier studies in which approximately 33-83% of patients were found to be hypertensive (10, 22, 23).

A common cause of systemic hypertension in Takayasu arteritis patients is renal artery stenosis, other contributory factors being atypical coarctation, decreased baroreceptor reactivity and decreased aortic capacitance. In patients with Takayasu arteritis as the inflammatory process progresses and gradually leading to stenosis and occlusion, more characteristics clinical features appear but at the same time, the development of collateral circulation may ameliorate some features.

Upper limb claudication was observed in 50% of the cases in the current investigation, with a quarter of the patients experiencing bilateral upper limb claudication. Lower limb claudication was observed in 28.4% of the patients. The current investigation is consistent with the Panja et al series, which found intermittent limb claudication in 25% of Takayasu arteritis patients (14). Upper limb claudication (53%) was shown to be more prevalentin our patients than lower limb claudication (15%), 43% of the patients had a variety of problems, with headache being the most prevalent. Approximately one-fifth of the patients had a history of tuberculosis.

In this study, we applied clinical and ACR criteria to diagnose Takayasu arteritis (10). Overall, 95% of patients satisfied clinical criteria, and 91% had an ACR score of 3. All study participants met at least one of the criteria (clinical or ACR). This is equivalent to modified criteria by Sharma et al, which have a sensitivity of 92.5% and ACR score 3, which has a sensitivity of 91% previously assessed. In 95% of patients, the ITAS score was more than (3, 11).

All 116 patients underwent computed tomography or conventional angiography. The subclavian artery was the most often affected vessel; aortic involvement was largely seen at the abdomen level, with higher involvement of the left subclavian artery compared to the right subclavian artery and larger involvement of the left common carotid artery compared to the right common carotid artery.

Reno-vascular hypertension is a common finding in Takayasu arteritis, occurring in 50% of patients. The main cause of hypertension in Takayasu arteritis patients is renal artery stenosis, but other variables such as atypical coarctation and decreased arterial wall elasticity also play a role. Renal artery stenosis reduces renal perfusion, resulting in increased renin secretion and aldosterone levels, which leads to salt and water retention and higher blood pressure.

Takayasu arteritis rarely involves the coronary arteries. Angiographic evidence of right and left renal artery stenosis was observed in 15% and 20% of patients, respectively, with bilateral renal artery involvement found in 29% of patients.

In previous study, Kumar et al. (24)  described that 9% to 11% coronary artery involvement in Takayasu arteritis presents as stenosis, occlusion or coronary artery aneurysm formation and mostly involving the ostia of the coronary arteries. In our cohort of 116 patients,  the coronary and pulmonary artery lesions were less commonly seen, in less than 20% of cases each. Yamada et al. (25) found 70% pulmonary artery involvement in the small series of 30 patients and noticed that the extent of arteritis in the major branches of the aorta appear to correlate with pulmonary artery involvement. Johnston et al.  (5) described 100% pulmonary artery involvement in Takayasu arteritis patients based upon method used to describe the pulmonary vasculature. Sharma et al. (26) studied pulmonary arterial anatomy in Takayasu arteritis patients using intravenous digital subtraction angiography) and found angiographically evident pulmonary arterial involvement in 14% patients and out of which 1/3rd of cases have abnormal chest radiographs. Takayasu pulmonary artery vasculopathy shows little correlation with the systemic pattern of arterial involvement.

Study limitations

Being a referral tertiary care center the population studied may not be perfect representative of actual incidence and prevalence of disease. The outpatients department  visits, admission and follow-up may have been mostly  constituted of the patients who underwent or had schedule for some kind of intervention.

Conclusion

Type V Takayasu arteritis was most common type (37%) of total study population. Hypertension and subclavian artery involvement both were seen in 2/3rd of population. Angiographic evidence of right and left renal artery stenosis was seen in 15% and 20% respectively, while bilateral renal artery involvement was found in 29% of patients.

Ethics:  The study has been approved by the institutional ethics committee (UNMICRC/CARDIO/2018/15).

Informed consent was obtained from all individual participants the manuscript

Peer-review: External and internal

Conflict of Interest:  The authors declared that there is no conflict of interest with any financial organization regarding the material discussed

Authorship:  J.S., T.S., D.J., R.C., P.R., V.S., H.U.,  K.P.l have equally contributed to preparation of manuscript and fulfill authorship criteria.

Acknowledgement and funding: This work was supported by U. N. Mehta Institute of Cardiology and Research Centre itself and received no specific grant from any funding agency, commercial or not for profit sectors.