Case 2: Acute Chest Pain in a 13-year-old Girl

Presented here are three patients who have a common chief complaint. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. Following the three cases, an expert weighs in in a short commentary with 5 questions for CME credit.A 13-year-old girl with obesity presents to the emergency department (ED) with acute-onset, left-sided chest pain at rest. The pain had developed just prior to her falling asleep, was intermittent throughout the night, and persisted on awakening the morning of presentation. The pain is “pressure-like,” is exacerbated by deep inspiration and lying supine, and improves with upright positioning. Just before presentation, she had 1 episode of emesis. She denies dyspnea, palpitations, cough, headache, dizziness, fever, recent illness, or recent vaccination. She takes no medications and has no history of chest pain or gastroesophageal reflux. She has no significant medical history and no chronic medical conditions.Her initial vital signs are as follows: temperature, 97.7°F (36.5°C); heart rate, 131 beats/min; respiratory rate, 20 breaths/min; blood pressure, 113/72 mm Hg (71st and 79th percentiles, respectively, for age, sex, and height); oxygen saturation, 100% on room air; weight 244.7 lb (111 kg) (>99th percentile); and BMI, 43.3 (>99th percentile). She is in mild distress on examination but is nontoxic-appearing. Examination of the neck shows no jugular vein distention and no lymphadenopathy. Cardiac examination reveals tachycardia without murmur or gallop and palpable distal pulses without peripheral edema. Pulmonary examination is notable for clear breath sounds bilaterally without rales or wheezing. Chest wall and back are nontender to palpation, with no obvious deformities. Her abdomen is soft and nontender. Organomegaly is difficult to assess given body habitus. There are no remarkable skin findings or Raynaud phenomenon.An electrocardiogram (ECG) obtained immediately on arrival at the ED shows sinus tachycardia with ST depression in the anterolateral and inferior leads along with ST elevation in aVR, concerning for acute ST-segment elevation myocardial infarction (Fig 1). Chest radiography reveals a partially imaged right lower lobe airspace consolidation, but otherwise no acute cardiopulmonary process. Laboratory evaluation in the ED is notable for leukocytosis (white blood cell count, 16,900/µL [16.9 × 109/L]), anemia (hemoglobin level, 9.9 g/dL [99 g/L]), thrombocytosis (platelet count, 557 × 103/µL [557 × 109/L]), elevated D-dimer level of 1.08 μg/mL FEU (reference range [RR], <0.5 μg/mL FEU), elevated high-sensitivity troponin level of 5,613 ng/L (5.6 µg/L) (RR, <14 ng/L [<0.04 µg/L]), and normal electrolyte levels on a basic metabolic panel. She is given an intravenous fluid bolus, and her tachycardia persists with the following repeated vital signs: heart rate, 133 beats/min; respiratory rate, 22 breaths/min; blood pressure, 109/94 mm Hg (55th and 99th percentiles for age, sex, and height, respectively); and oxygen saturation, 98% on room air. Shortly after, while awaiting transport to a pediatric tertiary care facility, she develops worsening tachypnea, hypoxemia, and rales on auscultation. She is given diuretics and placed on supplemental oxygen via a nonrebreather face mask. An echocardiogram obtained just before transfer reveals severely reduced systolic function of the left ventricle, with ejection fraction (EF) estimated to be 20% to 25% (RR, >55%), along with severe global hypokinesis.Chest pain is a common presenting complaint in the adolescent population that most often is benign and rarely indicates cardiac pathology. In a systematic review of more than 5,000 pediatric cases, the common causes of chest pain in the pediatric population were found to be idiopathic (35.6%), musculoskeletal (19.7%), psychological (16.3%), gastrointestinal (10.4%), cardiac (9.6%), and respiratory (8.4%); however, the authors noted a higher incidence of cardiac causes compared with previously published data, which estimated the incidence to be approximately 4% to 6% of cases. (1)(2) This patient’s constellation of symptoms, including chest pain, emesis, and dyspnea with fluid administration, are indicative of heart failure (HF) and, in fact, are the most frequently reported symptoms in adolescent HF. (3) In pediatrics, the 2 most common causes of HF are congenital heart disease and cardiomyopathy, (3) with cardiomyopathy being more likely in the previously healthy teenaged patient. The differential diagnosis for cardiomyopathy is quite broad, with the leading causes, in order of decreasing frequency, being idiopathic, myocarditis (infectious, medication- or toxin-induced, or inflammatory), neuromuscular diseases (such as Duchenne or Becker muscular dystrophy), familial (hypertrophic or dilated), and inborn errors of metabolism (such as fatty acid oxidation defects, glycogen storage diseases, and organic acidemias). Much less common causes include cardiac ischemia, structural cardiac defects, arrhythmias, hypertension, and autoimmune diseases. (4) Fortunately, the ST-segment changes on this patient’s ECG played a pivotal role in narrowing the differential diagnosis to myopericarditis and cardiac ischemia. Considering the regional ST depression on her ECG and lack of recent illness, ischemic cardiomyopathy was the leading cause of her symptoms, but the underlying etiology of ischemia remained unclear.On arrival at the pediatric cardiovascular ICU, her examination is notable for absence of palpable left brachial, left radial, and bilateral pedal pulses, but pedal pulses were auscultated with Doppler. Four-extremity blood pressures are as follows: left arm, 46/24 mm Hg; right arm, 89/60 mm Hg; left leg, 83/51 mm Hg; right leg, 99/61 mm Hg. Further laboratory evaluation reveals an elevated erythrocyte sedimentation rate (86 mm/hr [RR, 0–10 mm/hr]) and C-reactive protein level (5.9 mg/dL [59 mg/L] [normal high, <0.5 mg/dL (<5 mg/L)]). An echocardiogram shows a moderately dilated left atrium with mild to moderate mitral regurgitation, reduced systolic function of the left ventricle, and regional wall abnormalities, with EF estimated to be 35% to 40%. The origins and proximal courses of the left and right coronary arteries appear normal, and antegrade flow is noted. Last, there is a linear structure noted in the posterior portion of the aortic root, concerning for aortopathy. With these findings, along with evidence of cardiac ischemia already revealed on ECG, better visualization of the entire course of the coronary arteries and aorta is needed. A computed tomographic [CT] angiogram of the chest reveals luminal irregularity and a pseudoaneurysm of the mid-descending aorta and inflammatory enhancement of the mediastinal fat planes in this region (Fig 2). Also seen are inflammatory changes at the aortic root and the origin of the left main coronary artery, causing obvious narrowing (Fig 3). The mid- to distal left subclavian artery also shows significant inflammatory stranding with loss of the contrast column, indicating occlusion or at least very high-grade stenosis (Fig 4). The constellation of inflammatory changes is consistent with an inflammatory aortitis/vasculitis, and the overall pattern of distribution leads to a diagnosis of Takayasu arteritis (TA) (type IIb).TA, often called the “pulseless disease,” is a large-vessel vasculitis of unknown etiology primarily affecting the aorta and its major branches. It is a chronic, autoimmune, cell-mediated inflammatory disease causing intramural granulomatous inflammation, which can progress to stenosis, occlusion, and, occasionally, aneurysm formation. (5) Females are disproportionately affected, and peak onset is in the second or third decade of life. (6) Diagnosis is often delayed, as initial symptoms are nonspecific. In children and adolescents, specifically, the most common clinical features are hypertension (82.6%), headaches (31%), fever (29%), dyspnea (23%), weight loss (22%), and vomiting (20.1%). (7) As the disease progresses to the “burnt-out” phase, vessels become fibrotic and stenotic, causing clinical manifestations of ischemia. Diagnosis is most often made based on the American College of Rheumatology criteria from 1990, which require 3 of the following 6 criteria to be met (8): age at disease onset of 40 years or younger, claudication of extremity, decreased brachial artery pulse, systolic blood pressure difference greater than 10 mm Hg between arms, bruit over subclavian arteries or aorta, and arteriogram abnormality.Corticosteroids have long been the mainstay of therapy; however, recent case series and reviews of children with TA have demonstrated improved outcomes in patients treated with a combination of corticosteroids and conventional immunosuppressants or biological agents, although data are limited. (9) Recent recommendations from the European Alliance of Associations for Rheumatology attempted to provide a guideline for management of large-vessel vasculitides. (10) This includes the use of high-dose glucocorticoid therapy immediately for induction of remission and the consideration of combination treatment with disease-modifying agents, such as methotrexate, leflunomide, mycophenolate mofetil, azathioprine, and cyclophosphamide, at the time of diagnosis. In the event of relapsing or refractory disease, tocilizumab or tumor necrosis factor inhibitors are suggested as second-line agents. The decision to perform surgery in these patients is a difficult one, and the recommendation is to delay procedures until stable remission is achieved unless there is critical vascular ischemia or arterial vessel dissection. The mortality rate in children is estimated to be 7% to 35%, with extent of vessel involvement and severity of hypertension having the largest effect on prognosis. (7)(11)With imaging confirming the diagnosis, pediatric rheumatology immediately started high-dose methylprednisolone therapy, with the addition of infliximab and methotrexate the following day. The patient’s respiratory status and laboratory studies unfortunately worsened, with a troponin level increase from 2994 ng/L (3.0 µg/L) to 7202 ng/L (7.2 µg/L) on hospital day 3. A repeated CT angiogram showed 99% stenosis of her left main coronary artery, and she was taken emergently to the operating room for coronary revascularization of the left anterior descending and left circumflex arteries. She recovered and has since tolerated a prolonged corticosteroid taper, weekly subcutaneous methotrexate, and monthly infliximab infusions. A follow-up echocardiogram 9 months later revealed normal systolic function (EF, 57%) and ventricular size, with persistent wall motion abnormalities. She is also maintained on enalapril, atorvastatin, aspirin, and clopidogrel.Chest pain is a common presenting symptom in adolescents and indicates a cardiac cause in only 4% to 9.6% of patients. (1)(2) A thorough physical examination and electrocardiography are useful in triage of these patients to identify potential life-threatening conditions.Chest pain, dyspnea, nausea/vomiting, orthopnea, fatigue, and exercise intolerance are the most common signs of heart failure in adolescents. (3)Autoimmune conditions should be considered in adolescent girls with elevated inflammatory markers and constitutional nonspecific symptoms.