Myocardial infarction associated with pseudoephedrine use and acute streptococcal infection in a boy with normal coronary arteries

Abstract

A 16-year-old boy presented to the emergency department with chest pain. He had no history of other health problems and did not smoke. Acute myocardial infarction (AMI) in an adolescent boy with normal coronary arteries, associated with pseudoephedrine use and acute streptococcal infection, is reported. The diagnosis of AMI was based on typical electrocardiographic signs, enzyme changes and echocardiographic evaluation. Coronary vasospasm associated with pseudoephedrine use, endothelial dysfunction and prothrombotic state caused by acute streptococcal infection may be the mechanisms responsible for AMI in this case.

The possibility of AMI should be considered even in very young adolescents that have acute streptococcal pharyngeal infection, and it is important to obtain a complete history of the drugs used.

The leading cause of acute myocardial infarction (AMI) is coronary artery disease. However, 1% to 12% of patients who have had a myocardial infarction have angiographically normal coronary arteries (1). Young people are more likely to have a myocardial infarction with normal coronary arteries than older people (2). Although coronary vasospasm and concomitant thrombosis, endothelial dysfunction, platelet dysfunction, infectious and noninfectious coronary arteritis, genetic abnormalities, and vasospastic syndromes associated with Raynaud’s phenomenon and migraine headaches have been implicated (3), the etiology of myocardial infarctions without any coronary artery pathology is not understood. We report a 16-year-old boy with myocardial infarction with normal coronary arteries who was using the decongestant drug pseudoephedrine as symptomatic therapy for streptococcal infection of the upper respiratory tract.

CASE PRESENTATION

A 16-year-old boy was admitted to the chest pain unit of the emergency department of Usak State Hospital (Usak, Turkey) with chest pain lasting 4 h. He had no previous health problems, no family history of premature coronary artery disease, and he did not smoke. One day before this event, he had a sore throat from streptococcal upper respiratory tract infection. He took prescribed drugs, including cefazolin sodium 2 g/day, paracetamol 1500 mg/day and a nonprescription pseudoephedrine 180 mg/day. Approximately 20 h after the third dose (total dose 180 mg) of pseudoephedrine, a compressing retrosternal chest pain began. It started suddenly without prodromal symptoms and radiated to his left arm and back. At the time of admission, the patient was hemodynamically stable. The physical examination revealed that his blood pressure was 120/70 mmHg, pulse rate was 85 beats/min and regular, and cardiac auscultation was normal. There were no signs of heart failure. Acute bacterial infection of the pharynx, tonsils and paranasal sinuses was present. His 12-lead electrocardiogram (ECG) showed a regular sinus rhythm (84 beats/min) and ST segment elevation in leads II, III, aVF and V2 to V6 (Figure 1).

Figure 1).

Electrocardiogram on admission

Laboratory results revealed characteristics typical of myocardial necrosis and acute bacterial infection. Biochemical markers of myocardial necrosis showed a typical rise and fall. Troponin T measurement was positive (sensitivity greater than 1 ng/mL to 2 ng/mL) (Hegzagon, Human, Germany). Creatine kinase and creatine kinase-MB (normal ranges: 23 IU/L to132 IU/L and 0 IU/L to 6 IU/L, respectively) on admission were 642 IU/L and 61 IU/L, respectively, and peak values were 1221 IU/L and 121 IU/L, respectively.

Echocardiographic evaluation showed no signs of bacterial endocarditis, pericarditis or carditis of rheumatic fever, but did reveal a low ejection fraction (EF) (40%) and regional wall motion abnormalities of the left ventricle. The anterior, apical, lateral and inferior wall segments of the left ventricle were hypokinetic.

The use of cardiotoxic agents other than pseudoephedrine, such as cocaine, ergot derivates, alcohol or amphetamines, were excluded by the patient’s medical history. Therefore, this patient was diagnosed with myocardial infarction triggered by pseudoephedrine and acute bacterial infection.

The patient was initiated with nitroglycerine (intravenous [IV] infusion, titrated up to 40 μg/min), unfractionated heparin (IV bolus 5000 U and IV infusion under activated partial thromboplastin time control), acetylsalicylic acid (300 mg/day), clopidogrel (75 mg/day) and diazepam (10 mg/day). Because there were no changes in ST elevations and in symptoms after 15 min of nitroglycerine infusion (40 μg/min), thrombolytic therapy with tissue plasminogen activator was started. By the end of the thrombolytic therapy, the patient’s chest pain was less and ST elevation had decreased. Because the culture and antibiogram results revealed a group A beta hemolytic streptococcal infection sensitive to penicillin G, 12 million U/day IV infusion of penicillin G was administered for five days. The patient was then referred to an interventional cardiology centre for cardiac catheterization.

Coronary angiography results demonstrated definitely normal coronary arteries without any disturbance of blood flow (Figure 2). Catheter-induced spasm of the right coronary artery was observed and resolved without any intervention. Left ventriculography indicated normal size of left ventricle, low EF (45%), and inferior, lateral and apical hypokinesia of left ventricular wall.

Figure 2).

Angiographically normal coronary arteries

Based on these results, a diagnosis of non-Q wave myocardial infarction triggered by prolonged coronary vasospasm induced by pseudoephedrine use and acute streptococcal infection was considered likely. Thirty days after myocardial infarction, echocardiography revealed inferior and anterolateral hypokinesia of left ventricular wall motion and low EF (45%), and ECG showed persistent loss of R waves in leads II, III, aVF and V5 to V6 (Figure 3).

Figure 3).

Electrocardiogram 30 days after myocardial infarction

DISCUSSION

Cardiac deaths, especially due to AMI, are more common in cold winter months than in summer (4). There is also a seasonal distribution of AMI, with winter being the season of the highest incidence, and this correlates fairly well with the distribution of acute infection cases (5). A new large-scale study by Smeeth et al (6) provides support for the concept that acute infections are associated with a transient increase in the risk of vascular events like myocardial infarction. In that study, the risk of AMI was substantially higher after a diagnosis of systemic respiratory tract infection and was highest during the first three days (6).

In our patient, the febrile period before infarction raised the question whether myocarditis may have mimicked AMI in this case. The diagnosis of myocardial infarction in our patient was established by typical ECG changes, diagnostic elevation of myocardial enzyme levels and, most importantly, regional wall motion abnormalities on echocardiography performed on admission. Moreover, the pharyngeal culture revealed acute streptococcal infection.

Possible pathophysiological mechanisms by which acute infections may trigger AMI have been extensively discussed in the literature. Acute infection or inflammation impairs normal endothelial function. After the acute vasodilator stage of the illness, the residual inability of the endothelium to generate nitric oxide and prostanoids would change the balance of mediators produced in favour of vasospasm and thrombosis, and this effect, in turn, may be important in the pathogenesis of AMI (7). In healthy volunteers, a very brief exposure to endotoxin or certain cytokines impairs endothelium-dependent relaxation for many days. This effect has been termed endothelial stunning (8). These data suggest that endothelial dysfunction after acute infection or inflammation may be a transient risk factor for cardiovascular events, may trigger abnormal vascular behaviour, and may facilitate coronary vasospasm, particularly in association with certain drugs like pseudoephedrine.

Constriction of the coronary arteries is considered an important component in the pathogenesis of acute myocardial ischemia. Cysteinyl leukotrienes and thromboxane A2, produced in acute infections and inflammations, are potent vasoactive mediators able to modify cardiac and coronary function; in fact, they induce coronary artery constriction, which may be rapidly transient in normal people (9). The duration of this effect may be longer with the use of a potent vasoconstrictor drug like pseudoephedrine. Activation and aggregation of platelets may occur with high frequency in patients having streptococcal infection (10). These effects may have initiated AMI in this case. Thus, acute respiratory tract infections are associated with an increased risk of AMI for a period of approximately two weeks, even in people without a history of clinical risk factors for AMI such as in the present case (11).

Some drug effects associated with AMI have been reported in the medical literature. Ephedrine alkaloids (12) and pseudoephedrine (13–15) have been implicated in AMI. Mediators released by pseudoephedrine may cause vasospasm. Thus, pseudoephedrine may enhance the vasoconstrictor response of coronary arteries, especially when the patient has acute infection or inflammation of the respiratory tract. Several AMI cases associated with pseudoephedrine use have been reported in the medical literature (13–17). It appears that our patient is the youngest one.

CONCLUSION

This is the youngest reported AMI case associated with pseudoephedrine use, acute streptococcal upper respiratory system infection and angiographically normal coronary arteries. Coronary vasospasm associated with pseudoephedrine-containing medicine, endothelial dysfunction and prothrombotic state caused by acute streptococcal infection may be possible responsible mechanisms. The possibility of AMI should be seriously considered even in very young adolescents with acute streptococcal respiratory tract infection, and it is very important to obtain a complete history of all drugs used.