Cannabis-Induced Third-Degree AV Block

Background Cannabis (marijuana) is the most widely consumed illicit drug in Europe. However, many are unaware of its potential cardiovascular side effects. Case Report A 19-year-old man presented to the emergency department with palpitations and presyncope after smoking cannabis. A third-degree atrioventricular block (complete heart block) was diagnosed. We believe cannabis exposure to have been the likely cause. Extensive work-up—including Borrelia and auto-immune serology, CT coronary angiography, magnetic resonance imaging, and electrophysiological study—was negative. The patient was initially treated with IV isoprenaline. Within one day, the bradycardia spontaneously resolved. The patient was advised to quit using cannabis. No further therapy was initiated. We discuss the clinical presentation, pathophysiology, and evidence from the literature linking cannabis exposure to bradycardia. Conclusion We describe a case of third-degree atrioventricular block after cannabis use. Emergency physicians should be aware of the potential cardiovascular side effects of this drug.


Introduction
ird-degree atrioventricular block is defined by a lack of transmission of the impulse from the atria to the ventricles, due to an anatomical or functional impairment in the conduction system. e etiology includes ischemic heart disease, cardiomyopathy, myocarditis, degenerative disease (Lenegre-Lev syndrome), infiltrative processes, congenital heart disease, congenital AV block, metabolic causes (hyperkalemia, hypoxia, thyroid dysfunction), increased vagal tone, cardiac procedures, drugs (beta-blockers, nondihydropyridine calcium channel blockers, antiarrhythmics) and toxins (cardiac glycosides). e incidence increases with advancing age [1]. A few reports have described atrioventricular block in young patients without underlying cardiac disease, following cannabis use [2][3][4][5][6].
Cannabis (marijuana) is the most widely consumed illicit drug in Europe [7]. While the psychoactive effects of cannabis are well known, few people are aware of its potential cardiovascular side effects. Many patients are seeking treatment for their cannabis use disorder, but somatic investigations are seldom performed [8].
We describe a patient presenting to the emergency department with third-degree atrioventricular block (complete heart block) a er cannabis use.

Case Presentation
A 19-year-old man presented to the emergency department with palpitations and presyncope. He experienced three episodes of near complete loss of consciousness in the last few hours prior to presentation. Each episode had lasted for less than thirty seconds and had been accompanied by palpitations. One hour before symptom onset, the patient had smoked a joint. He had been using cannabis since 2 years, on average 2-3 joints per week. Never before had he experienced syncope or presyncope. He had no past medical history except for autism spectrum disorder diagnosed at age 11 and he was not taking any medication. Family history was negative for sudden death or pacemaker implantation.
On clinical examination, the patient appeared well. He had no fever (36.9°C), oxygen saturation at room air was 99%, respiratory rate 20/min, and blood pressure 120/70 mmHg. On initial examination, heart rate was 100 beats per minute. Heart sounds were normal without murmurs, lung auscultation was clear and the remainder of the clinical exam was unremarkable.
Initial electrocardiogram (ECG) showed intermittent sinus rhythm and junctional tachycardia up to 120 beats per minute. During observation, ECG monitoring showed several episodes of third-degree atrioventricular block, with underlying sinus rhythm but without ventricular escape. ese episodes, the longest of which lasted 7.2 s (Figure 1) provoked the same symptoms as the patient had described.
An isoprenaline (isoproterenol) infusion was started at 0.5 mcg/min and the patient was admitted to the coronary care unit. e isoprenaline infusion was stopped a er one day without recurrence of bradycardia. e patient was observed for 4 days, without any further events. ECG at discharge was normal. Echocardiography at presentation and at discharge was normal. Chest X-ray was unremarkable. CT angiography showed no coronary anomaly or stenosis. Cardiac magnetic resonance imaging showed no structural abnormalities or areas with late gadolinium enhancement. Electrophysiological (EP) study was entirely normal and showed a normal atrioventricular conduction time.
Cannabis-induced atrioventricular block was suspected. e patient was advised to quit using cannabis. No further therapy was initiated. Follow-up 5-day ambulatory ECG monitoring, a er cessation of cannabis use, showed normal sinus rhythm without atrioventricular block, apart from physiological Wenckebach phenomenon.

Discussion
We described a young and otherwise healthy patient who presented with third-degree atrioventricular block a er using cannabis. e temporal association with exposure and spontaneous resolution a er cessation of cannabis use were suggestive for a causal role. Cannabis-induced atrioventricular block remains an elimination diagnosis. Other notable causes, such as hyperkalemia, hypothyroidism, Lyme's disease, sarcoidosis, myocarditis, coronary artery disease, and congenital heart disease, were all excluded in the present case.
Cannabis has become increasingly popular, especially among youngsters. According to the European Monitoring Centre for Drugs and Drug Addiction, 6.8 % of 15-to 64-year olds have used cannabis in the past year and 3.6% in the last month [7]. Decriminalization of cannabis possession and communication about the potential therapeutic properties of medicinal cannabinoids have contributed to the perception of cannabis as a harmless (or even "healthy") substance. Yet, cannabis is increasingly recognized as a potential underlying cause of cardiovascular emergencies in young patients without other cardiovascular risk factors, including arrhythmia [9][10][11], myocardial infarction [12], cardiomyopathy, stroke [13], and cardiac arrest [14][15][16][17]. e cardiovascular effects of cannabis depend on several factors, including exact composition of the substance, route of administration, dose, and duration of use [18]. Δ 9 -Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, has biphasic effects on the cardiovascular system [19]. At low to moderate doses, it leads to a surge in sympathetic activity causing tachycardia and hypertension, while parasympathetic activity is predominant at higher doses, causing bradycardia and hypotension.
While cannabis-induced sinus bradycardia is a well-documented phenomenon [6], severe bradycardia leading to (pre) syncope is rare. To date, 10 reports have been published (PubMed search using the strategy: ("cannabis" OR "marijuana") AND ("atrioventricular block" OR "av block" OR "heart block" OR "cardiac arrest" OR "bradycardia" OR "asystole" OR "sick sinus syndrome"), see Table 1). e bradycardia was sinus arrest in six [20][21][22][23][24][25], second-degree AV block in two [2,4], and third-degree AV block in two [3,5]. With the exception of Menahem et al. 's case [21], all occurred in patients without any past cardiological history. None of the patients were taking any medication. Outcome was favorable in all these reports, with spontaneous resolution a er cessation of cannabis exposure. However, cannabis has been implicated as a cause of sudden cardiac death [12,14,15,21,26]: although most of these deaths are probably linked to myocardial infarction, cannabis-induced bradycardia might have played a role in some.
In conclusion, we reported a case of third-degree atrioventricular block in a young and otherwise healthy patient following cannabis use. Emergency physicians should be aware of the potential cardiovascular side effects of this drug.

Consent
We have obtained informed consent from the patient for publication of this case.

Conflicts of Interest
e author declares that they have no conflicts of interest.