Takayasu’s Arteritis Presenting as Heart Failure in a 19-Year-Old Female

Abstract

This report presents the case of this atypical presentation of a rare disease in a 19-year-old female with cardiomyopathy and hypertension. Investigation revealed renovascular stenosis, infarcts, and active vasculitis pathognomonic for Takayasu arteritis (TA). Cardiac magnetic resonance imaging demonstrated mild pericardial inflammation and epicardial edema. Vasculitis-induced renovascular secondary hypertension resulted in myocardial dysfunction, which recovered with treatment of hypertension and TA. (Level of Difficulty: Beginner.)

Graphical abstract

This report presents the case of this atypical presentation of a rare disease in a 19-year-old female with cardiomyopathy and hypertension. Investigation revealed renovascular…

History of Presentation

A 19-year-old previously healthy Asian female was admitted for newly diagnosed heart failure with reduced ejection fraction (HFrEF). Two months prior to admission, she developed a persistent, dry cough followed by fatigue, anorexia, muscle cramps, and orthopnea. She denied chest pain, abdominal pain, fevers, night sweats, hemoptysis, joint pains, rash, hair loss, weight loss, oral or vaginal ulcers, visual changes, eye pain or redness, headaches, or syncope.

Learning Objectives

• •To consider Takayasu’s Arteritis in young women with new onset heart failure and secondary hypertension.
• •To relate the pathophysiology of Takayasu’s Arteritis to subsequent end-organ damage.

On initial examination, she was afebrile with blood pressure 172/106 mm Hg, heart rate of 98 beats per min, oxygen saturation of 100% without supplemental oxygen, respiratory rate of 21 breaths/min, and body mass index of 19 kg/m². She appeared fatigued. She had no tenderness to palpation over the forehead, and her conjunctiva were clear. There were no oral ulcerations or cervical lymphadenopathy. The jugular venous pulse was elevated to 9 cm of water. The heart rate was regular, with a normal S1 and S2, with no murmurs or S3 gallop. There were bibasilar lung crackles. There were symmetrical peripheral pulses, equal blood pressures in both arms, no peripheral edema, and no skin or nail changes. The remainder of the examination revealed no abnormalities.

Medical History

She denied any significant past medical history, medication use, allergies, travel, substance use, or sexual activity. Family history was negative for cardiovascular, autoimmune, rheumatologic, or thrombotic disease.

Differential Diagnosis

The initial differential diagnosis included viral myocarditis and cardiomyopathy secondary to severe hypertension. Her history and symptoms were not concerning for substance abuse, genetic cardiomyopathy, or ischemic heart disease.

Investigations

Initial laboratory evaluation was notable for a troponin-I concentration elevated to 0.11 ng/ml, which peaked at 1.87 ng/ml over 48 h, brain natriuretic peptide concentration of 493 pg/ml, white blood cell count of 11.5 (1,000 U/l), and concentrations of hemoglobin at 9.9 g/dl, potassium at 3.0 mEq/l, and creatinine at 1.3 mg/dl, and an elevated erythrocyte sedimentation rate and C-reactive protein at 55 mm/h and 12.7 mg/l, respectively (Table 1). Chest radiography revealed pulmonary edema with bilateral pleural effusions. Transthoracic echocardiography revealed a left ventricular ejection fraction (LVEF) of 15% and left ventricular dilation with end-diastolic dimension of 5.5 cm (reference range 3.9 to 5.3 cm) and multiple calcified apical mural thrombi. There was no left ventricular hypertrophy. The right ventricle demonstrated normal function, and there was no significant valvular disease.

Table 1.

Basic Laboratory Studies: Comprehensive Metabolic Panel

	Value	Reference Range
Laboratory study
Sodium	135	135–145 mmol/l
Potassium	3	3.5–5 mmol/l
Chloride	92	98–107 mmol/l
Carbon dioxide	30	22–31 mmol/l
Blood urea nitrogen	10	5–25 mg/dl
Creatinine	1.3	0.6–1.1 mg/dl
Estimated glomerular filtration rate	59	>59 ml/min/1.73 m2
Calcium	9.8	8.9–10.1 mg/dl
Magnesium	2.1	1.6–2.6 mg/dl
AST	53	5–34 U/l
ALT	66	0–55 U/l
Alkaline phosphatase	79	52–144 U/l
Total bilirubin	0.4	0.1–1.2 mg/dl
Lactate	0.7	0.5–2.2 mmol/l
Albumin	3.1	3.5–5.5 g/dl
LDL	96	<130 mg/dl
HDL	28	>49 mg/dl
Complete blood count
Laboratory study
Hemoglobin	9.9	11.6–15.4 g/dl
Platelets	454	150–450 (1,000) U/l
White blood cells	11.5	4–11 (1,000) U/l
Mean corpuscular value	76.3	80–100 fl
Cardiac enzymes
Laboratory study
Troponin I	0.11	<0.04 ng/ml
BNP	493	<100 pg/ml
Inflammatory markers
Laboratory study
Erythrocyte sedimentation rate	55	<20 mm/h
C-reactive protein	12.7	<5 mg/l
Iron studies
Laboratory study
Ferritin	41.47	4.63–204 ng/ml
Iron	14	50–170 μg/dl
Total iron binding capacity	308	225–420 μg/dl
Percent saturation	5	15%–60%

ALT = alanine aminotransferase; AST = aspartate aminotransferase; HDL = high-density lipoprotein; LDL = low-density lipoprotein.

Cardiac magnetic resonance (CMR) imaging was notable for possible perimyocarditis with only epicardial edema and minimal late gadolinium enhancement. Clinical presentation, imaging, and elevated inflammatory markers prompted rheumatologic serological studies and hypercoagulable workup, which were unrevealing (Table 2).

Table 2.

Rheumatologic Serologic Studies and Hypercoagulability Studies

Laboratory Study	Value	Reference Range
ANA	1:40	<1:40 titer
RF	<15	<20 IU/ml
CCP	<20	<20 U
dsDNA	<10	<10 titer
RNP	2	<20 U
Smith Ab	3	<20 U
SSA Ab	1	<20 U
SSB Ab	2	<20 U
MPO	<1	<1 AI
PR3	<1	<1 AI
ANCA	<10	<10 titer
Scl-70	2	<20 U
Transglutaminase IgA	<1	<1 U/ml
C3C	133	83–193 mg/dl
C4C	31	15–57 mg/dl
IgA	296	65–421 mg/dl
IgG serum	1,031	552–1,631 mg/dl
IgM	66	33–293 mg/dl
Lupus anticoagulant (hexagonal)	3.1	<12 s
Factor V Leiden	Negative	Negative
Cardiolipin Ab IgG	<10	<20 GPL
Cardiolipin Ab IgM	<10	<20 MPL
Cardiolipin Ab IgA	<10	<20 APL
Beta 2-glycoprotein 1 IgG	<10	0–20 SGU
Beta 2-glycoprotein 1 IgM	<10	0–20 SMU
Beta 2-glycoprotein 1 IgA	<10	0–20 SAU
Cryoglobulins	Negative	Negative
Protein C activity	87	70%–130%
Protein S activity	73	65%–140%

AI = antibody index units; ANA = anti-nuclear antibodies; ANCA = anti-neutrophil cytoplasmic antibodies; APL = anti-phospholipid antibodies; C3C = complement component 3; C4C = compliment component 4; CCP = cyclic citrullinated peptide; dsDNA = double-stranded DNA; GPL = IgG phospholipid units; MPL= IgM phospholipid units; MPO = myeloperoxidase; PR3 = proteinase 3; RF = rheumatoid factor; RNP = ribonucleoprotein; SAU = standard IgA beta-2 glycoprotein unit; Scl-70 = sclero-70; SGU = standard IgG beta-2 glycoprotein unit; Smith Ab = Smith antibody; SMU = standard IgM beta-2 glycoprotein unit; SSA Ab = Sjogren's Syndrome related antigen A antibodies; SSB Ab = Sjogren's Syndrome related antigen B antibodies.

A secondary hypertension investigation was pursued, given her young age, new onset severe hypertension, and end-organ dysfunction. Laboratory study results were pertinent for urine and plasma metanephrines of 287 μg/24 h and <0.20 nmol/l, respectively, both within normal ranges, and an elevated serum aldosterone and renin activity (115 ng/dl and 26.1 ng/ml/h, respectively) but with a normal ratio of 4.40. The presence of renal dysfunction prompted a vascular ultrasonography examination which demonstrated no perfusion to the left kidney. Computed tomography angiography results demonstrated embolic infarcts in the right kidney and complete occlusion of the left renal artery with an atrophic left kidney suggestive of chronic ischemic change (Figure 1), a narrowed aorta (0.7 cm) at the level of the diaphragm with post-stenotic dilation (Figures 2 and 3), and stenosis of the celiac artery with post-stenotic dilation (Figure 3). CMR revealed 50% stenosis of the proximal right renal artery and superior mesenteric artery and mural enhancement of the mid-abdominal aorta and renal arteries consistent with active vasculitis. Invasive coronary angiography demonstrated normal epicardial coronary arteries.

Figure 1.

CTA of the Abdomen and Pelvis

Global hypoperfusion of the left kidney without focal area of infarct. The right kidney has several areas of peripheral cortical hypoperfusion. CTA = computed tomography angiography.

Figure 2.

CTA of the Abdomen and Pelvis

The descending thoracic aorta narrows to 7 mm in the lower chest before mild aneurysmal dilation to 15 mm. CTA = computed tomography angiography.

Figure 3.

3D Reconstruction from CTA

Imaging demonstrated aortic stenosis and dilation, a 5-mm segment of complete occlusion just beyond the origin of the left renal artery with a distal artery diameter of 2.5 mm and celiac artery stenosis with post-stenotic dilation to 7 mm. CTA = computed tomography angiography.

Management

TA was diagnosed based on imaging. The diagnosis of TA is rarely made by biopsy, given the impracticality of large vessel biopsy in the absence of planned vascular intervention. It was postulated that profound hypertension from TA led to the patient’s severe myocardial dysfunction. She was treated with anticoagulant agents for the ventricular thrombi, and diuresis resulted in improvement in cough and orthopnea. For treatment of hypertension and initiation of guideline-directed therapy for HFrEF, an angiotensin-converting enzyme inhibitor and beta-blocker therapy was initiated. Intravenous pulsed solumedrol was given for induction of remission followed by high-dose prednisone at 1 mg/kg daily according to European League Against Rheumatism recommendations (1).

Discussion

This case represents an atypical presentation of TA in a young Asian woman with HFrEF and severe hypertension. Left ventricular dilation, ventricular thrombi, and atrophic left kidney suggested disease chronicity, and imaging was consistent with TA. TA is a rare disease, presenting typically in Japanese females in the second or third decade of life 2, 3. TA damages vasculature through transmural infiltration of arterial walls by inflammatory cells, causing granuloma formation. In the sclerotic phase, intimal fibroplasia and medial scarring forms stenotic regions, and degeneration of elastic fibers forms dilated regions (4). Classically, TA affects large vessels, specifically the aortic arch and its major branches (2), although coronary artery involvement occurs in 5% to 10% of patients (5).

Secondary hypertension has been reported in 33% to 83% of TA patients (6) and is one of its most common clinical manifestations 3, 4. The mechanism of hypertension in TA is not well defined but likely involves mechanical vascular obstruction, neural activation of baroreceptors from aortic arch involvement, and hormonal factors (3). TA involves the renal arteries, resulting in stenosis in 23% to 31% of cases (7), which likely leads to activation of the renin-angiotensin-aldosterone-system (RAAS), contributing to severe hypertension.

Heart failure has been described as a comorbidity in 13.2% of TA patients (8). In a cohort of 54 Japanese patients, secondary hypertension was prevalent in 37% of patients, and the cause of death in 7 of 8 patients was heart failure or stroke (9). TA can cause heart failure through inflammatory myocarditis, but more commonly, it is caused by renovascular secondary hypertension (10).

In the present case, subacute cardiomyopathy and elevated inflammatory markers and troponin initially suggested a primary pathology of myocarditis. However, cardiac CMR demonstrated only minimal myocardial inflammation. Severe hypertension and renal dysfunction led to a secondary hypertension evaluation and vascular imaging, which demonstrated mural enhancement consistent with an active vasculitic process as well as the pathognomonic stenotic and aneurysmal lesions of TA.

Follow-Up

After 3 months of steroid therapy, the patient was slowly transitioned to methotrexate therapy as a steroid-sparing agent. Repeated echocardiograms at 3 months demonstrated LVEF of 42% with resolved apical thrombi, followed by complete myocardial recovery at 6 months. Repeated magnetic resonance angiography showed no evidence of active vasculitis.

Conclusions

This case demonstrates HFrEF as the initial presentation of TA. This patient’s cardiomyopathy was precipitated predominantly by secondary hypertension, with mild perimyocarditis extending only into the epicardial space. The mechanisms by which TA results in severe hypertension includes mechanical vascular obstruction, baroreceptor activation, and RAAS activation. In this case, complete myocardial recovery was achieved with guideline-directed medical therapy, adequate blood pressure control, and immunosuppression for TA.