Unusual association of diseases/symptoms

Case Report

Ischaemic cardiomyopathy and embolic stroke
in a young adult with suspected synthetic
cannabinoid use
Sumera Khan,1 Ahmad Hanif,2 Michael F Wilson3,4
1

Roswell Park Cancer Institute,
Buffalo, New York, USA
2
Department of Medicine,
Roswell Park Cancer Institute,
Buffalo, New York, USA
3
University at Buffalo – The
State University of New York,
Buffalo, New York, USA
4
Nuclear Cardiology and
Cardiovascular Computed
Tomography, Kaleida Health
Hospitals, Buffalo, NY, USA
Correspondence to
Dr Ahmad Hanif,
​ahmad.​hanif@​roswellpark.​org
Accepted 18 May 2018

Summary
The incidence of cardiovascular disease is increasing in
young adults. We are reporting a case of acute stroke in
a young patient with severe ischaemic cardiomyopathy
in the absence of traditional risk factors. After ruling out
atherosclerotic disease, his presentation was attributed
to synthetic cannabinoid use. We then discussed the
typical barriers in early diagnosis and limitations of
laboratory testing in this condition. Due to the increase
in abuse of these synthetic drugs among young adults,
there is a need for high clinical suspicion which can
help with early recognition and improve morbidity and
mortality associated with these chemicals.

Background
Coronary artery disease (CAD) is the leading cause
of mortality in the USA and worldwide. An estimated
14.8 million people in the USA carry a diagnosis of
CAD.1 Most of the cases are diagnosed in people aged
≥65 years. Recent data suggest a decrease in hospitalisations in the USA due to myocardial infarctions
among elderly population, however, the same trend
is not observed for young adults.2 3 We are writing
this case to emphasise on the less known risk factors
in young adults which may lead to cardiovascular
disease. An accurate history is essential for timely
diagnosis which can significantly decrease long-term
morbidity and mortality.

Case presentation

To cite: Khan S, Hanif A,
Wilson MF. BMJ Case Rep
Published Online First:
[please include Day Month
Year]. doi:10.1136/bcr-2018224755

A 25-year-old African American male resident of a
correctional facility was brought to the emergency
room with acute-onset confusion, right-sided weakness with bowel and bladder incontinence. He was
asymptomatic prior to the start of this episode. He
did not report any medical problems and denied any
family history of cardiac or neurological diseases.
He had a 5 years history of cigarette smoking and
quit 2 years ago. Staff from correctional facility
expressed concerns about the use of synthetic
marijuana as he was found on the bathroom floor
with a suspicious substance lying next to him. The
officers also gave a history of about five previous
episodes of confusion without neurological deficits
after exposure to synthetic cannabinoids over the
last 6 months. On examination, he was found to be
confused with left gaze deviation and right hemiparesis. His cardiovascular and pulmonary examination was otherwise unremarkable.

Investigations
The results of blood cell count and routine serum
chemistries were within normal limits. Lipid
panel showed total cholesterol of 126 mg/dL
(7.0 mmol/L), low-density lipoprotein (LDL) level
of 67 mg/dL (1.73 mmol/L) and triglycerides 34 mg/
dL (0.383 mmol/L). Haemoglobin A1c was normal
at 5.5%. The antinuclear antibody (ANA) screen
was negative in blood. The results of serum and
urine toxicology screen using immunoassay came
back negative. A 12-lead electrocardiogram (EKG)
revealed Q-waves in leads II, III and AVF along
with poor progression of R-wave. CT scan of head
showed a large subacute ischaemic left middle cerebral artery infarct with associated cerebral oedema
suspicious for cardioembolic stroke. Echocardiogram showed severely reduced left ventricular
ejection fraction (EF) of 20%–30% with periapical
akinesis and severe hypokinesis of the mid to apical
anterior wall. There was no evidence of left ventricular thrombus or patent foramen ovale on echocardiography. Cardiac enzymes were cycled three
times and remained negative. During the hospital
course, he was noted to have swelling of left upper
extremity and a Doppler ultrasound showed acute
deep venous thrombosis in the left brachiocephalic
vein. Further hypercoagulable workup revealed a
high coagulation factor VIII activity level of 384%.

Differential diagnosis
In a young individual with a normal lipid profile
and no family history of premature CAD, the
diagnosis of acute ischaemic stroke along with
ischaemic cardiomyopathy triggered workup for
unusual causes. Due to reports of synthetic marijuana use from correctional facility, the diagnosis
of cannabinoid-induced cardiovascular disease was
considered. He was also found to have a high factor
VIII protein activity level which can be associated
with venous as well as arterial thrombosis leading to
ischaemic strokes and myocardial infarction.4 Lastly
there is possibility of genetic mutations affecting
cholesterol transfer pathways resulting in premature CAD although we did not obtain genomic
testing on this patient.

Treatment
The working diagnosis was acute embolic stroke
with chronic ischaemic cardiomyopathy due to
synthetic cannabinoid use. Decompressive left

Khan S, et al. BMJ Case Rep 2018. doi:10.1136/bcr-2018-224755

1

Unusual association of diseases/symptoms
Discussion

Figure 1 Cardiac stress imaging with Tc99m. Tomographic images
revealing a large size, severe in intensity infarct within the mid to apical
anterior, mid to apical inferior and apical segments. There is additionally
mild intensity, small in size inferolateral peri-infarct ischaemia, with
a sum difference score of 2. Visually normal TID of 0.76. Polar display
confirms tomographic results. Gated images reveal periapical akinesis,
severe hypokinesis of the mid to apical anterior wall, as well as
moderate global hypokinesis. TID, transient ischaemic dilation.

craniectomy was performed for cerebral oedema with improvement in mental status. The patient was started on secondary
stroke prevention with aspirin and atorvastatin along with
lisinopril and metoprolol for heart failure with reduced EF.
He was not started on anticoagulation for DVT due to high
risk for intracranial bleeding. His weakness improved with
physical therapy and he was discharged to acute rehabilitation
centre.

Outcome and follow-up
The patient was lost to follow-up after discharge and re-established care 1 year later. He was started on anticoagulation
for hypercoagulable state. His neurological deficits initially
improved with physical therapy and then remained stable. For
further evaluation of cardiomyopathy, a myocardial perfusion
scan was obtained with Tc99m after Regadenoson stress which
showed a large infarct involving the apical, apical anterior
and apical inferior segments with mild peri-infarct ischaemia
(see figure 1).
2

This is an interesting case of a young adult with significant
cardiovascular disease in the absence of traditional risk factors
of smoking, obesity, diabetes, hypertension and family history.
In our case, the presumptive diagnosis of synthetic cannabinoid-induced myocardial infarction and ischaemic stroke was
made based on a clinical history. Despite the negative urine toxicology, the suspicion of synthetic cannabinoids use remained the
most probable diagnosis since traditional toxicology immunoassays aimed at detecting tetrahydrocannabinol (THC), the active
ingredient in marijuana, are often not able to detect synthetic
variants of illicit drugs.5 An interesting finding in this case was
the high level of factor VIII protein activity which is associated with venous thromboembolism but arterial clot formation
is rare. Furthermore, factor VIII levels can be elevated in the
setting of acute inflammation and hence, this diagnosis remained
low on our differential .
Synthetic cannabinoids (also known as K2 or Spice) are a
heterogeneous group of street drugs that are different from THC
in chemical structures and potency but activate the same cannabinoid receptors in brain creating a euphoric high after inhalation
or ingestion.6 Multiple studies have demonstrated the increased
risk of myocardial infractions and ischaemic strokes with use of
synthetic cannabinoids.7–11 Other frequent side effects reported
with synthetic cannabinoid use are anxiety, psychosis, tachycardia, bradycardia, chest pain, hypotension, syncope, acute
tubular necrosis and thromboangiitis obliterans.12–16 The mechanism of cardiovascular side effects is largely unknown but
thought to be related to haemodynamic stress caused by synthetic
cannabinoids due to their sympathomimetic effect. These can
include tachyarrhythmias, hypertension, postural hypotension
and arterial spasm.17
Synthetic cannabinoids are classified as schedule I substances
by Drug Enforcement Administration (DEA). However, its use
among young adults in the USA is increasing due to ease of
availability and cheap cost.18 In our case, the use of this drug
may be the cause of severe ischaemic cardiomyopathy and
ischaemic stroke with permanent right-sided weakness, thus
leading to severe morbidity in a young adult. There is a need
for education among general public and healthcare providers
regarding the dangers associated with the use of synthetic
drugs. The development of immunoassays aimed at detecting
these drugs in serum or urine will also help in stratifying the
population at-risk. However, the diversity among different
drugs under this common umbrella of ‘synthetic marijuana’
will remain a barrier to successful testing of all chemicals with
a single battery of tests.

Learning points
►► Synthetic cannabinoids are human-made chemicals that all

bind to cannabinoid receptors, but vary significantly in their
structure and side-effects profile.
►► Their use has been associated with development of
cardiovascular disease in the absence of traditional risk
factors.
►► Traditional toxicology immunoassays are often not able to
detect synthetic variants of illicit drugs.
►► Cardiovascular disease in young adults should prompt a
careful investigation into family history, inherited disorders
of cholesterol metabolism, hypercoagulability and substance
abuse.

Khan S, et al. BMJ Case Rep 2018. doi:10.1136/bcr-2018-224755

Unusual association of diseases/symptoms
Contributors All authors contributed to the writing of this manuscript. SK wrote
the case report and discussion. AH performed the literature search. MFW edited the
paper and did final approval.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article)
2018. All rights reserved. No commercial use is permitted unless otherwise expressly
granted.

References

1 Kochanek KD, Murphy SL, Jq X, et al. Deaths: Final data for 2014. National vital
statistics reports. Hyattsville, MD: National Center for Health Statistics, 2016:65:4.
2 Chen J, Normand SL, Wang Y, et al. Recent declines in hospitalizations for acute
myocardial infarction for Medicare fee-for-service beneficiaries: progress and
continuing challenges. Circulation 2010;121:1322–8.
3 Gupta A, Wang Y, Spertus JA, et al. Trends in acute myocardial infarction in
young patients and differences by sex and race, 2001 to 2010. J Am Coll Cardiol
2014;64:337–45.
4 Kamphuisen P, Eikenboom J, Bertina R. Elevated Factor VIII Levels and the Risk of
Thrombosis. Arteriosclerosis. Thrombosis2001;21:731–8.
5 Franz F, Angerer V, Jechle H, et al. Immunoassay screening in urine for synthetic
cannabinoids - an evaluation of the diagnostic efficiency. Clin Chem Lab Med
2017;55:1375-1384.
6 Montecucco F, Di Marzo V. At the heart of the matter: the endocannabinoid system in
cardiovascular function and dysfunction. Trends Pharmacol Sci 2012;33:331–40.
7 Jouanjus E, Leymarie F, Tubery M, et al. Cannabis-related hospitalizations:
unexpected serious events identified through hospital databases. Br J Clin Pharmacol
2011;71:758–65.

8 Wolff V, Lauer V, Rouyer O, et al. Cannabis use, ischemic stroke, and multifocal
intracranial vasoconstriction: a prospective study in 48 consecutive young patients.
Stroke 2011;42:1778–80.
9 Jouanjus E, Lapeyre-Mestre M, Micallef J. French Association of the Regional
Abuse and Dependence Monitoring Centres (CEIP-A) Working Group on Cannabis
Complications*. Cannabis use: signal of increasing risk of serious cardiovascular
disorders. J Am Heart Assoc 2014;3:e000638.
10 Hemachandra D, McKetin R, Cherbuin N, et al. Heavy cannabis users at elevated
risk of stroke: evidence from a general population survey. Aust N Z J Public Health
2016;40:226–30.
11 Rumalla K, Reddy AY, Mittal MK. Recreational marijuana use and acute ischemic
stroke: A population-based analysis of hospitalized patients in the United States. J
Neurol Sci 2016;364:191–6.
12 Hoyte CO, Jacob J, Monte AA, et al. A characterization of synthetic cannabinoid
exposures reported to the National Poison Data System in 2010. Ann Emerg Med
2012;60:435–8.
13 Martin-Blondel G, Koskas F, Cacoub P, et al. Is thromboangiitis obliterans presentation
influenced by cannabis addiction? Ann Vasc Surg 2011;25:469–73.
14 Hermanns-Clausen M, Kneisel S, Szabo B, et al. Acute toxicity due to the confirmed
consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction
2013;108:534–44.
15 Waugh J, Najafi J, Hawkins L, et al. Epidemiology and clinical features of toxicity
following recreational use of synthetic cannabinoid receptor agonists: a report
from the United Kingdom National Poisons Information Service. Clin Toxicol
2016;54:512–8.
16 Bhanushali GK, Jain G, Fatima H, et al. AKI associated with synthetic cannabinoids: a
case series. Clin J Am Soc Nephrol 2013;8:523–6.
17 Müller HH, Kornhuber J, Sperling W. The behavioral profile of spice and synthetic
cannabinoids in humans. Brain Res Bull 2016;126:3–7.
18 Riederer AM, Campleman SL, Carlson RG, et al. Acute Poisonings from Synthetic
Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 20102015. MMWR Morb Mortal Wkly Rep 2016;65:692–5.

Copyright 2018 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit
http://group.bmj.com/group/rights-licensing/permissions.
BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission.
Become a Fellow of BMJ Case Reports today and you can:
►► Submit as many cases as you like
►► Enjoy fast sympathetic peer review and rapid publication of accepted articles
►► Access all the published articles
►► Re-use any of the published material for personal use and teaching without further permission
For information on Institutional Fellowships contact consortiasales@bmjgroup.com
Visit casereports.bmj.com for more articles like this and to become a Fellow

Khan S, et al. BMJ Case Rep 2018. doi:10.1136/bcr-2018-224755

3