Suspected Cannabis-Induced Acute Coronary Syndrome and Advanced Heart block

Abstract

We describe a 35-year-old Caribbean-Black male patient with a significant cannabis history who presented with an inferior ST-segment-elevation acute coronary syndrome (STE-ACS), with advanced heart block during active, ongoing cannabis consumption. During primary percutaneous coronary intervention, cineangiography revealed substantial thrombus burden in the first acute marginal branch of the right coronary artery. He successfully underwent aspiration thrombectomy with subsequent angioplasty with a drug-coated balloon and guideline-directed medical therapy, including direct oral anticoagulation. The clinician should be cognizant of the association between ACS and both acute and chronic cannabis consumption.

Introduction

Cannabis has been used for many decades; however, increased legalization, medical applications and indications have seen unprecedented global stratospheric consumption. ¹ Derived from the Cannabis sativa plant, which contains numerous chemical compounds, 2 subclasses, delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are primarily attributable for the majority of its effects.^2,3 Medical cannabis has been utilized chiefly for its anti-inflammatory effect via reduced expression of pro-inflammatory interleukins (ILs), among other modulatory pathways. ³

Conversely, cannabis smoking is associated with autonomic dysfunction such as sympathetic stimulation as well as parasympathetic inhibition, increased endogenous inflammation, platelet reactivity, and carboxyhemoglobin generation. ⁴ Thus, cannabis use has been linked to major adverse cardiovascular events (MACEs) such as acute coronary syndromes (ACSs), atrial fibrillation (AF), ventricular fibrillation (VF), cerebrovascular events (CVEs), and pulmonary embolism (PE).^5,6

We describe a 35-year-old Caribbean-Black patient with significant cannabis use who presented with an inferior ST-segment-elevation (STE)-ACS, with advanced heart block during active, ongoing cannabis consumption. This underscores the importance of being aware that cannabis use is implicated in thrombosis and severe bradyarrhythmias with devastating clinical sequelae.

Case Presentation

A 35-year-old Caribbean-Black male with no significant medical history presented to the emergency department with new-onset, severe, unstable angina after actively smoking cannabis. The chest pain was exacerbated by physical activity, with no alleviation with rest for ~3 hours. He also experienced presyncope, dyspnea, and emesis, though notably without palpitations or syncope. The patient denied any familial history of premature coronary artery disease or sudden cardiac death. His social history revealed chronic cannabis use, with a long-term history of consumption averaging 8 to 10 times daily over the past 20 years; however, he denied alcohol, tobacco, heroin, and cocaine use. He did not report any recent prior infection or occupational exposure to toxins as a construction worker.

On presentation, his vital signs were: blood pressure of 157/96 mm Hg, heart rate of 52 beats/minute, tachypnea at 22 breaths/minute with an oxygen saturation of 98% on room air, and an afebrile temperature. The patient was alert and coherent, with no focal neurological deficits. Cardiovascular examination revealed abnormal, irregular, and sometimes absent heart sounds (S₁ and S₂) without additional sounds or murmurs. His jugular venous pulse was not elevated, and there was no sacral or pedal edema. His apical impulse was undisplaced with a diminished, tapping character. Respiratory examination indicated bilateral vesicular breath sounds without wheezing or crackles. An initial 12-lead electrocardiogram (ECG) performed revealed 3 mm STE in leads II, III, and aVF) and complete heart block at 46 beats/minute, followed by posterior and right-sided ECGs (Figure 1A-C). An emergent high-sensitivity cardiac troponin I was significantly elevated at 5092 ng/L (normal range: 0-20 ng/L). Other immediate investigations, such as a complete blood count, renal, hepatic function tests, glycated hemoglobin, lipid panel, and thyroid cascade, were normal in the acute clinical scenario. A bedside 2-dimensional transthoracic echocardiogram revealed inferior hypokinesis with a mildly reduced left ventricular ejection fraction of 40% to 45%, normal right ventricular systolic function and no severe valvular heart disease or pulmonary hypertension.

Figure 1.

The patient’s 12-lead ECGs. (A) A standard ECG demonstrating 3 mm STE in leads II, III, and aVF and complete heart block at 46 beats/minute. (B) A posterior ECG demonstrating very subtle STE in leads II, III, and aVF and near negligible in V7, V8, and V9, with ongoing complete heart block. (C) A right-sided ECG demonstrating subtle ST-segment depression with T-wave inversion in V3R, V4R. (D) A post-PPCI ECG demonstrating sinus rhythm with resolved STE and subtle, nonspecific ST-T changes. ECGs, electrocardiograms; PPCI, primary percutaneous coronary intervention; STE, ST-segment-elevation.

The patient proceeded directly to primary percutaneous coronary intervention. Coronary cineangiography via the distal right transradial approach (“snuffbox” approach) revealed normal left coronary arteries but Thrombolysis in Myocardial Infarction (TIMI) grade 1 flow in the acute marginal (AM) branch 1 of the right coronary artery with TIMI grade 4 thrombus (Figure 2A and B). Using standard interventional technique, initial manual aspiration thrombectomy was performed (Export™ Aspiration Catheter, Medtronic plc, Minneapolis, Minnesota, United States) with subsequent percutaneous transluminal coronary angioplasty (PTCA; due to the small caliber of the artery) with a drug-coated balloon (AGENT™ Drug-Coated Balloon; Boston Scientific, Marlborough, MA, USA) with a good angiographic result (TIMI 3 flow) and no complications (Figure 2C). The patient’s telemetry almost immediately demonstrated sinus bradycardia, which justified deferring temporary transvenous pacing at this juncture. Postprocedure, a 12-lead ECG displayed sinus rhythm with resolved STE (Figure 1D). He was admitted to the cardiac care unit, where he was initiated on comprehensive, guideline-directed medical therapy for his inferior STE-ACS, which comprised aspirin 81 mg, clopidogrel 75 mg, rivaroxaban 5 mg twice daily, rosuvastatin 40 mg, enalapril 2.5 mg twice daily, finerenone 20 mg, empagliflozin 25 mg, and colchicine 0.5 mg. Ticagrelor and beta-blockers were avoided due to their potential to exacerbate the bradycardia.

Figure 2.

The patient’s PPCI. (A) The patient’s left coronary arteries (LAD artery and LCx artery) are angiographically normal with TIMI 3 flow. (B) TIMI grade 1 flow in the acute marginal branch 1 of the RCA with TIMI grade 4 thrombus (encircled in red with red arrow). (C) Using standard interventional technique, initial manual aspiration thrombectomy was performed (Export™ Aspiration Catheter; Medtronic plc, Minneapolis, MN, USA) with subsequent PTCA with a DCB (AGENT™ Drug-Coated Balloon; Boston Scientific, Marlborough, MA, USA) with a good angiographic result (TIMI 3 flow) and no complications (red rectangle with red arrow). DCB, drug-coated balloon; LAD, left anterior descending; LCx, left circumflex; PPCI, primary percutaneous coronary intervention; PTCA, percutaneous transluminal coronary angioplasty; RCA, right coronary artery; TIMI, Thrombolysis in Myocardial Infarction.

During his ensuing 48-hour hospitalization, his clinical status improved as he did not experience any adverse cardiovascular symptoms or display any features of incipient heart failure or further lethal arrhythmia. His preliminary workup for autoimmune conditions and thrombophilia returned negative, with the caveat of being on optimal antithrombotic therapy. He was safely discharged after being extensively counseled with respect to lifestyle modification, medication adherence, and stringent cannabis cessation. On routine cardiology outpatient clinic 2 weeks later, he did not report any interval serious adverse events and remained abstinent from cannabis usage.

Discussion

Cannabis, a generic, colloquial term for the psychoactive component of the plant C. sativa, constitutes the most extensively cultivated, trafficked, and consumed illicit substance worldwide.^7,8 With respect to public health impact, the annual prevalence of its usage is estimated at circa 150 million individuals, ~2.5% of the global adult population. ⁹ The physiological effects are primarily attributable to a specific class of compounds known as cannabinoids. Among the hundreds of these identified active cannabinoids, CBD and THC are the most prevalent and well-characterized. Their effects are mediated through the endocannabinoid (CB) system, a complex signaling network.^10,11 This system involves CB receptors, which are widely dispersed throughout the body, such as the central and peripheral nervous systems, as well as platelets, myocytes, skeletal muscle, liver, pancreas, and adipose tissue. ¹²

An emerging body of evidence alludes to a robust correlation between cannabis use and ACS. Several studies have reported signals for MACE, mostly among hospitalized patients with inherent selection bias, with relative risks approaching 1.1 to 2.5. ¹⁰ Epidemiological data reveal a significant increase in ACS-related hospitalizations and associated inpatient mortality among cannabis users. ¹³ Additionally, frequent cannabis use is associated with markedly elevated odds of CVEs.^14,15 While cannabis smoking is largely perceived as a benign recreational activity, evidence suggests that it may be linked to adverse cardiometabolic effects. The primary psychoactive component, THC, acutely stimulates the CB system, with arrhythmogenic potential, leading to arrhythmias such as AF. This pro-arrhythmic derangement is primarily driven by the activation of myocardial CB1 receptors, which not only generates a direct tachycardic response but also induces a shift in autonomic tone toward increased sympathetic activity. ¹⁶ The accentuated sinus node automaticity and altered cardiac electrophysiology synergistically elevate the potential for dysrhythmias. ¹⁷ There is also mounting evidence of an association between cannabis consumption and bradycardia, sinus pauses, and orthostatic hypotension.^18,19 Endocannabinoids exhibit intricate, complex cardiomodulatory effects, possibly conferring cardioprotection during myocardial ischemia by attenuating sympathetic neurotransmission. Paradoxically, their action on transient receptor potential vanilloid 1 (TRPV1) receptors initially triggers a sympathomimetic response characterized by hypertension and tachycardia, followed by a later phase of hypotension and bradycardia. Electrophysiologically, these compounds can inhibit ventricular conduction, as evidenced by prolonged QRS complexes, with the resultant sequelae of conduction blocks.^20,21

The association between smoking and atherosclerosis is well established. ²² Recent research has identified and underscored the role of the inflammasome in the progression of this disease. ²³ Specifically, NLR family pyrin domain containing 3 (NLRP3), an intracellular sensor, detects a wide range of pathogen-associated molecular patterns and damage-associated molecular patterns, including adenosine triphosphate, cholesterol crystals, oxidized mitochondrial deoxyribonucleic acid, cyclic guanosine monophosphate-adenosine monophosphate, and nanoparticles. The activation of NLRP3 promotes the formation of the NLRP3 inflammasome, which is involved in critical pro-inflammatory pathways and neurohormonal milieu. ²⁴ THC can induce a prothrombotic state by modulating key factors within the coagulation cascade, potentially transitioning the hemostatic balance toward hypercoagulability.^25-27 It has also been implicated in platelet hyperreactivity by activating cannabinoid receptors.^28-30 Smokers exhibit markedly elevated levels of inflammatory cytokines, such as tumor necrosis factor-alpha and IL-1β. ³¹ Additionally, both active and passive smoking have been shown to increase serum levels of C-reactive protein. ³²

Our case was interesting from several aspects. The patient stated that his cannabis was not mixed or laced with other compounds; however, we could not ascertain the veracity of his self-reported use, and it is well-documented that these added substances can be implicated with adverse cardiovascular effects. Although the patient had TIMI 4 thrombus, it was unclear at the time whether this was an in situ, de novo thrombosis as a result of his recent cannabis binge with a resultant procoagulant state, or possibly an embolic phenomenon from an episode of occult, undetected AF, which his excessive consumption may have precipitated. Additionally, the patient’s complete heart block was postulated to be a sequel of AM occlusion, as it immediately resolved with successful thrombectomy and PTCA, as opposed to an intrinsic effect of TRPV1 receptors. Ultimately, this case underscores that cannabis, far from being a benign recreational drug, can result in MACEs, including thrombosis and severe, life-threatening bradyarrhythmias. The patient’s acute-on-chronic cannabis use was likely the major contributory factor for his ACS, as his diagnostic investigations did not reveal any conventional or atypical cardiac risk factors. As societal consumption of cannabis increases, clinicians must heighten their index of suspicion for cannabis-related cardiac complications. This approach necessitates comprehensive substance use history-taking and targeted patient education to address this emerging public health concern.

Conclusion

This case illustrates a compelling temporal association between acute-on-chronic cannabis use and a severe, multifaceted cardiac event in a young adult with no conventional cardiovascular risk factors. The patient’s presentation of an inferior STE-ACS, complicated by advanced heart block and substantial coronary thrombus burden, underscores the potent cardiometabolic, prothrombotic and arrhythmogenic potential of cannabis. Additionally, this report emphasizes the need for clinicians to systematically enquire about cannabis use in this subpopulation of patients, as it may represent a crucial modifiable risk factor influencing both acute management and long-term secondary prevention strategies.