Clenbuterol-induced myocarditis in a young man desiring to lose weight

Background

Myocarditis is a challenging diagnosis due to the heterogeneity of clinical presentations, which can range from mild symptoms of chest pain and palpitations associated with transient electrocardiographic changes to life-threatening cardiogenic shock and ventricular arrhythmias.1 Although its aetiology often remains undetermined, a large variety of infectious agents, systemic diseases, drugs and toxins can cause the disease. Clenbuterol is a long-acting beta-2 agonist sometimes used as an illicit substance for weight loss and performance enhancement. Awareness of the medical community regarding its potential side effects is essential, as its consumption has been shown to be increasing among the young.2 This case report seeks to illustrate the adverse cardiovascular events associated with clenbuterol and to alert competent authorities towards the regulation of its use and discontinuation of illegal distribution.

Case presentation

A previously healthy young man in his late 20s was presented to the emergency department with a 2-day history of persistent pleuritic chest pain and shortness of breath associated with diaphoresis, restlessness, palpitations, vomiting and polydipsia. He denied fever, cough or other constitutional symptoms. Notably, these symptoms started shortly after the ingestion of a sole pill containing 400 μg of clenbuterol hydrochloride (10 times the recommended adult therapeutic dose of 40 μg/day),2 which he took only once and for the first time, as he desired to lose weight and gain lean muscle mass. He denied the use of other performance enhancement substances or illicit drugs. He did not have a history of cardiovascular risk factors, such as hypertension, dyslipidaemia, cigarette smoking nor family history of premature cardiovascular disease.

Physical examination at presentation was unremarkable. The patient was afebrile, with normal breathing rate, blood pressure of 124/76 mm Hg and heart rate of 87 beats per minute. Cardiac auscultation revealed normal heart sounds and the absence of heart murmurs.

Investigations

Laboratory workup revealed leucocytosis (14.4×10⁹/L, normal range 4–10×10⁹/L) with neutrophilia (11.6×10⁹/L; 80.4%, normal range 40%–80%) and an elevated C reactive protein (9.5 mg/dL, normal range <0.5 mg/dL) together with increased high sensitivity cardiac troponin T (hs-cTnT 400 ng/L, normal range <14 ng/L), creatine kinase (546 U/L, normal range <190 U/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP 775 pg/mL, normal range <125 pg/mL); the remaining laboratory data were normal and SARS-CoV-2 real-time PCR test was negative. Toxicological screening for misused drugs was also negative for cocaine and amphetamines. The 12-lead ECG showed a normal sinus rhythm with concave ST elevation in lateral and inferior leads (V4-V6, DI, aVL and DII) and slight PR depression (figure 1). Chest X-ray was unremarkable. Given this clinical scenario a diagnosis of myopericarditis was highly suspicious and the patient was admitted to the cardiology ward for further workup.

Initial bedside transthoracic echocardiography (TTE) showed a non-dilated, non-hypertrophied left ventricle with normal left ventricular ejection fraction (LVEF) and a small area of hypokinesia in the apical inferior wall. No pericardial fluid was observed. Cardiac magnetic resonance (CMR) was performed to support the clinical suspicion and to rule out alternative diagnoses, showing signs of myocardial oedema and subepicardial delayed enhancement in the inferior and inferolateral walls, suggestive of acute myocarditis (figure 2). A detailed panel of cardiotropic viruses was performed, with negative results.

Differential diagnosis

In the clinical setting of acute chest pain with ST segment elevation and elevated cardiac biomarkers, the case for an acute coronary syndrome (ACS) should always be kept in mind. However, the patient’s age, absence of cardiovascular risk factors, type and duration of chest pain together with elevated inflammatory parameters and the temporal association with the ingestion of clenbuterol made this scenario less likely. Since the patient was clinically stable, a CMR was performed to determine chest pain aetiology, eliciting findings suggestive of a myocarditis as opposed to an ACS. Consequently, due to the perceived low clinical likelihood of underlying obstructive coronary artery disease, no anatomical coronary anatomy assessment was performed.

Other causes of acute chest pain that should be included in the differential diagnosis include a stress reaction or panic disorder, since the patient had no risk factors for cardiovascular disease and his symptoms resembled those found in these disorders. Nevertheless, clinical history, ECG testing and laboratory workup revealed significant changes that excluded this hypothesis. Additionally, other chest pain aetiologies such as pulmonary embolism, diffuse oesophageal spam, pneumothorax, pneumonia and aortic dissection were also considered, but clinical presentation, medical history, physical examination and the result of investigations promptly excluded these hypotheses.

Furthermore, patients with acute pericarditis and myocarditis can complain of similar symptoms, and just the elevation of cardiac troponin can steer the diagnosis toward the latter. Despite the strong temporal association with clenbuterol use, other myocarditis aetiologies should be considered, namely viral or toxic myocarditis. These were excluded with a detailed panel of cardiotropic viruses and a thorough clinical history. Ultimately, only an endomyocardial biopsy would give a definite diagnosis. However, the risk/benefit ratio of this procedure was deemed unfavourable. Nevertheless, considering the clinical presentation, a clenbuterol-induced myocarditis was the most likely diagnosis.

Treatment

The patient was managed conservatively by the discontinuation of clenbuterol and temporary use of an anti-inflammatory agent (acetylsalicylic acid, 750 mg every 8 hours) and beta-blocker therapy. Anti-emetics and intravenous fluids were also administered as supportive care. After stabilisation, he was discharged on beta-blocker therapy alone, since pericardial involvement was ruled out by CMR, and avoidance of strenuous physical activities was advised for 3–6 months.

Outcome and follow-up

Clinical course was uneventful and the patient recovered completely. Chest pain and shortness of breath remitted within several hours after admission and the patient was asymptomatic for the remaining days of hospitalisation. No cardiac arrhythmias were detected during hospital stay. Cardiac troponin and NT-proBNP levels peaked at day 3 of hospitalisation (hs-cTnT maximum of 953 ng/L and NT-proBNP maximum of 959 pg/mL) and were within normal range at discharge. The patient was discharged home after 7 days in a stable and asymptomatic condition.

At 6 months follow-up, he is doing well without symptomatic recurrence. Repeat TTE showed normal LVEF without regional wall motion abnormalities and repeat CMR revealed resolution of myocardial oedema and substantial reduction of the delayed enhancement area (figure 3). He resumed his physical activities uneventfully.