A rare case of acute myocardial infarction with a non-specific symptom in a young female with systemic lupus erythematosus

Abstract

A 31-year-old female with an 18-year history of systemic lupus erythematosus (SLE) complained of epigastralgia and consulted the emergency outpatient department at our hospital. Her physical examination revealed tenderness at the scrobiculus cordis, which was a non-specific symptom of coronary heart disease (CHD). We ultimately gave a diagnosis of acute myocardial infarction based on coronary angiography and performed percutaneous coronary intervention. Although pre-interventional intravascular ultrasound demonstrated distinct atherosclerotic lesions in the coronary arteries, there were no atherosclerotic lesions in other systemic arteries. Although CHD in young SLE patients is a significant cause of morbidity and premature death, it tends to be misdiagnosed because their symptoms may be non-specific. In addition, this case highlights the fact that even SLE patients with no systemic atherosclerosis are at risk for the development of CHD.

<Learning objective: Coronary heart disease (CHD) in young systemic lupus erythematosus (SLE) patients is a significant cause of morbidity and premature death, but it tends to be misdiagnosed because their symptoms may be non-specific. Moreover, SLE patients are at risk for the development of CHD.>

Introduction

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown cause that can affect the skin, joints, lungs, nervous system, serous membranes, and/or other organs of the body. Cardiac involvement includes pericarditis, Libman–Sacks endocarditis, myocarditis, and, most critically, coronary heart disease (CHD). Among patients with SLE, CHD is most commonly due to atherosclerosis, since they have an increased prevalence of atherosclerosis secondary to systemic inflammation and the adverse effects of long-term glucocorticoid treatment. In autopsy studies, substantial atherosclerosis was found to be present in up to half of young patients with SLE [1], [2]. The present case highlights the need to recognize that patients with SLE are at high risk for CHD, even if they are young.

Case report

A 31-year-old woman was admitted with epigastralgia. She had no smoking history and was not obese (body mass index 18.7 kg/m²). She had symptoms of SLE at age 13 years and this was complicated with lupus nephritis within a year. She also presented with hypertension and dyslipidemia at about the same time that she developed lupus nephritis, which were treated with losartan potassium 25 mg/day and pitavastatin 2 mg/day, respectively. Although SLE was treated with 6 mg of prednisolone, 150 mg of mizoribine, and 3 mg of tacrolimus hydrate taken orally daily, she showed finger-joint swelling before one week prior to admission. Due to the exacerbation of SLE, the daily dose of prednisolone was increased from 6 mg to 15 mg, and her joint swelling improved. She also exhibited epigastralgia 4 days before admission. Her intermittent pain became continuous pain and she consulted the emergency outpatient department at our hospital. On admission, her level of consciousness was clear and her blood pressure was normal (120/80 mmHg), whereas she had sinus tachycardia (100 beats per minute) and hyperventilation (20 times/minute). A physical examination revealed tenderness at the scrobiculus cordis, although the results of cardiac and pulmonary auscultation were normal. Chest radiography showed a cardiothoracic ratio of 56% in the supine position, and there was no pleural effusion or pulmonary congestion. There were no abnormal findings on imaging, including abdominal radiography and computed tomography (CT). In a blood examination, anticardiolipin antibody was negative and prothrombin time and activated partial thromboplastin time were normal. Cardiac enzymes were elevated [white blood cell count (WBC) 134,00/μL; differential WBC count: neutrophil 11,400/μL, lymphocyte 1179/μL; aspartate aminotransferase 76 U/L, lactate dehydrogenase 288 U/L, creatine kinase (CK) 518 U/L, CK-myocardial band 40.5 ng/mL, troponin T positive]. Serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride were 104, 35, 50 and 52 mg/dL, respectively, and casual blood glucose and hemoglobin A1c (US National Glycohemoglobin Standardization Program) were 93 mg/dL and 5.4%, respectively. Other significant laboratory findings included normal renal function with a creatinine level of 0.7 mg/dL and a normal anti-double stranded DNA antibody level of 7.7 IU/mL (normal, 0–12 IU/mL). Urine protein and occult blood reaction were both negative (spot urine protein/spot urine creatinine 0.09 g/g creatinine). Hypocomplementemia [C3 57 mg/dL (normal, 73–138 mg/dL), CH50 23 U/mL (32–58)], and mild elevation of C-reactive protein [0.4 mg/dL (0–0.3)] were present. Electrocardiography showed ST-segment elevations in V1-4 and T wave inversion in I, aVL, and V2-6 (Fig. 1), and echocardiography showed akinesia of the anteroseptal wall and the apex of the left ventricle (Fig. 1A,B); the left ventricular ejection fraction (LVEF) was determined to be 44% using Simpson’s method. Based on these findings, we gave a diagnosis of acute myocardial infarction (AMI). After the oral administration of crushed aspirin 200 mg and clopidogrel sulfate 300 mg, she underwent emergent coronary angiography, which revealed severe stenosis (99%) with thrombolysis in myocardial infarction (TIMI) grade 2 at the proximal left anterior descending coronary artery (LAD) (Fig. 2C,D). The right coronary artery was intact angiographically, and the posterior descending artery was collateral to the LAD (Fig. 2E). The attenuated coronary plaque that corresponded to the above lesion was documented by intravascular ultrasound assessment (Fig. 3). We performed percutaneous coronary intervention (PCI) [stent implantation (MULTI-LINK 3.0 × 30 mm)] and the coronary flow in the LAD improved to TIMI grade 3. Although the CK levels increased to 605 U/L, heart failure did not develop. Beginning the day after PCI, aspirin and clopidogrel sulfate were decreased to 100 mg/day and 75 mg/day, respectively, and continued thereafter. Since her systolic blood pressure was low (80–90 mmHg), we discontinued the oral administration of losartan potassium. In its place, we initiated the daily oral administration of bisoprolol fumarate at 0.625 mg/day for the treatment and prophylaxis of cardiac remodeling. As for steroid therapy, the daily oral dose of prednisolone at 15 mg was continued, and rheumatoid symptoms suggesting the exacerbation of SLE did not develop during hospitalization. After leaving the intensive care unit, she underwent cardiac rehabilitation and the degree of her systemic atherosclerosis was evaluated. Her ankle brachial pressure index and brachial ankle pulse wave velocity were 1.16 and 1041 m/s on the left, and 1.08 and 1007 m/s on the right, which were within the respective normal ranges. Carotid ultrasonography showed no progression of intimal thickness (max intima-media thickness of the common carotid artery was 0.45 mm on the left, and 0.55 mm on the right), and enhanced thoracoabdominal CT did not show obvious atherosclerosis or arterial calcification in the thoracoabdominal aorta or bilateral renal arteries. There was no obvious atherosclerosis in the systemic arteries, except for the coronary arteries. She was discharged after 22 days of hospitalization, and was receiving prednisolone, mizoribine, and tacrolimus hydrate for SLE and pitavastatin, aspirin, clopidogrel sulfate, and bisoprolol fumarate for the secondary prevention of CHD. Follow-up electrocardiography and echocardiography performed 1 year later in the outpatient department showed that the abnormal findings recognized at the time of onset of AMI were within the normal range (Fig. 4A–C).

Fig. 1.

Electrocardiography on admission.

Fig. 2.

Diastole (A) and systole (B) as assessed by echocardiography on admission. White arrow heads show akinesia of the left ventricular anteroseptal wall and apex. Coronary angiography showed 99% stenosis of the proximal left anterior descending coronary artery (LAD) (C, D) and an intact right coronary artery (E) on admission. White arrows show severe stenosis of the LAD, and black arrow shows collateral circulation from the right posterior descending artery to the LAD.

LA, left atrium; LV, left ventricle.

Fig. 3.

Intravascular ultrasound showed attenuated coronary plaque corresponding to severe stenosis.

Fig. 4.

Electrocardiography (A) and echocardiography (B; diastole, C; systole) performed 1 year after discharge in the outpatient department. There was no asynergic motion of the left ventricle. The left ventricular ejection fraction was 74% using Simpson’s method.

Discussion

We experienced a rare case of CHD with a non-specific symptom in a young patient with SLE, which highlighted the following considerations.

First, we should recognize that patients with SLE are at high risk of CHD, which is a significant cause of morbidity and premature death even in patients who are young. Manzi et al. reported that women with SLE aged 35–44 years had a >50-fold elevated risk of myocardial infarction compared to those of a similar age without SLE in the Framingham Offspring Study [3]. In patients with SLE, CHD is most commonly due to atherosclerosis, although other causes such as coronary arteritis, coronary artery spasm, and hypercoagulability related to anticardiolipin antibodies have been reported [4]. The pathogenesis of accelerated atherosclerosis is likely multifactorial, and includes systemic inflammation by SLE and the adverse effects of long-term glucocorticoid treatment. Korkmaz et al. investigated myocardial infarction in 50 young (35 years ≥) SLE patients and suggested that the inflammation associated with SLE itself could promote coronary atherosclerosis [5]. They divided their patients into three subgroups according to the type of coronary involvement [Group I: normal coronary artery or coronary thrombosis (n = 16); Group II: coronary aneurysm/arteritis (n = 12); Group III: coronary atherosclerosis (n = 22)] and compared their clinical features. The lag time between the onset of SLE manifestations and the development of MI (mean ± SD, months) varied: Group I (34 ± 45) < Group II (69 ± 54) < Group III (124 ± 100). They suggested that, as SLE progresses, the type of coronary involvement may change from no occlusive coronary events or coronary thrombosis to vascular wall inflammation and finally coronary atherosclerosis. In addition, long-term glucocorticoid treatment results in hyperlipidemia, hypertension, and obesity. For example, in a cross-sectional study of 264 SLE patients, after adjusting for age, weight, and antihypertensive drug use, a 10 mg/day increase in the dose of prednisone led to increases in serum cholesterol, mean atrial blood pressure, and body weight of 7.5 mg/dL, 1.1 mmHg, and 2.5 kg, respectively [6]. Our patient had a long lag time of 18 years (216 months) between the onset of SLE and the development of MI, which was longer than that in the above Group III. In addition, hyperlipidemia and hypertension complicated with glucocorticoid treatment were present for 17 years. We considered that these factors could have been associated with the development of MI.

Second, CHD may be present with a non-specific symptom in patients with SLE. Twenty-eight SLE female patients without any cardiovascular symptoms/signs were investigated using technetium-99m sestamibi single-photon emission computed tomography [7]. Perfusion abnormalities were detected in 12 of the asymptomatic SLE patients (43%). In this case, MI was present with tenderness at the scrobiculus cordis, which was a non-specific symptom of CHD. We initially suspected abdominal disease, and gave priority to an abdominal examination over electrocardiography. As a result, there was a delay in the diagnosis of CHD. Therefore, we should recognize that CHD may be present in SLE patients with non-specific symptoms. For SLE patients who visit the emergency room due to acute symptoms (abdominal, back, shoulder, and pleuritic pain, dyspnea, diaphoresis, etc.), we may wish to give priority to electrocardiography over other examinations, even if this appears to be an overreaction.

Third, it is important to differentiate whether CHD is due to premature atherosclerosis or to coronary arteritis because, while coronary intervention is necessary in the former, the signs and symptoms of myocardial ischemia may improve under the administration of glucocorticoids and immunosuppressive drugs in the latter [8]. Englund and Lucas reported that coronary angiography may be useful for distinguishing between these lesions, and angiographic findings that include the presence of aneurysms, the occurrence of multiple segmental narrowings, and the total occlusion of intramural coronary arteries all favor a diagnosis of coronary arteritis [9]. On the other hand, however, both lesions may coexist in the same coronary arteries, as suggested in an autopsy study by Takayanagi et al., who reported that atherosclerotic lesions and inflammatory lesions coexisted in the coronary arteries [10]. Although coronary angiography may be useful for distinguishing between these conditions, it does not allow imaging of the coronary microvasculature where the pathophysiology may lie [11]. Thus, it may be difficult to clearly differentiate between them, and we assume that both lesions may coexist in many cases of CHD in patients with SLE. Consequently, when we treat CHD in SLE patients who may have both lesions, we should consider interventions to address both the stenosis of coronary arteries and active SLE disease, which indicate PCI and an increase or addition of glucocorticoids and/or immunosuppressive drugs. In this case, we considered that CHD was mainly due to premature atherosclerosis in the absence of the above angiographic characteristics that would support coronary arteritis. However, since we could not completely exclude the possibility of complicating coronary arteritis because the development of CHD coincided with the active phase of SLE, we treated the patient with an increased dose of prednisolone (15 mg/day) in addition to PCI. We addressed both pathologies, and a good course was observed afterwards.

Lastly, while we found distinct atherosclerosis in the coronary arteries, there was no atherosclerosis in the other systemic arteries including the aorta, carotid arteries, renal arteries, and extremital arteries. Although it has been reported that atherosclerotic plaques in the carotid arteries are found more often in patients with SLE than in age- and sex-matched controls [12], in this case, there was no progression of intimal thickness in the carotid arteries. Although the reason for the abnormal distribution of atherosclerosis in this case is not clear, it suggests that even SLE patients with no evidence of systemic atherosclerosis are at risk for the development of CHD.

In conclusion, we continued the administration of dual-antiplatelet therapy (aspirin and clopidogrel sulfate) for the secondary prevention of CHD and are planning to perform periodic noninvasive tests including exercise electrocardiography and stress myocardial scintigraphy or coronary CT angiography.

Conflict of interest/disclosure

KS is a Chief Director and SM is a Director of NPO Clinical and Applied Science, Fukuoka, Japan. KS has an Endowed “Department of Molecular Cardiovascular Therapeutics” supported by MSD, Co. LTD. SM belongs to the Department of Molecular Cardiovascular Therapeutics supported by MSD, Co. LTD.