I remain very interested in the cardiac and brain complications of medications and substances that are commonly used to get high or create altered states. I am also very interested in the popular trend to characterize cannabis as some previously undiscovered medication that can cure everything ranging from anxiety to obstructive sleep apnea. I was naturally interested when I saw this paper (1) looking at the issue of incident atrial fibrillation and common intoxicants.
The authors examine a very large database in California
that included anyone who had been seen in an emergency department, ambulatory
surgery center, or hospital over a period of 10 years (2005-2015). After they eliminate minors, subjects with
persistent atrial fibrillation, and subjects with missing data they had a total
of 23,561,884 people. 998,747 of those people had incident atrial
fibrillation (defined as the first encounter for atrial fibrillation). Since their study design is a retrospective
observational study they also recorded substance use was considered present if Substance
use was considered present if there was coding for any indication of use of
methamphetamine, cocaine, opiates, or cannabis.
Knowing the atrial fibrillation and substance use diagnoses – the
authors calculate the hazard ratio for each of the substances of interest.
Hazard ratios are basically the ratio of the people exposed to intoxicants who developed atrial fibrillation over the unexposed who developed atrial fibrillation. So any number greater than 1 means that the population exposed to intoxicants had greater risk. The corrected hazard ratios were noted to be 1.86
(methamphetamine), 1.74 (opioids), 1.61 (cocaine), and 1.35 cannabis. The
authors adjusted for common atrial fibrillation risk factors and ran an
additional negative control analysis and looked at the scatter of data pints
for these 4 substances and hazard ratios of developing appendicitis, connective
and soft tissue sarcoma, and renal cell carcinoma and showed no consistent
pattern for these illnesses.
There are a couple of interesting considerations relevant
to this study. The first is the
mechanism of action in each case. With stimulants there is a direct hyperadrenergic
effects and depending on the individual and dose of the drug varying degrees of
tachycardia, palpitations, and hypertension.
Long term users frequently end up with cardiomyopathy from these effects
and in some cases ventricular arrhythmias and congestive heart failure. There
can also be acute vascular effects like ischemia either due to the increased
cardiac demand or pre-existing arteriosclerosis. Atrial fibrillation has not
typically been placed in that group of morbidities from stimulant use. Patient with
atrial fibrillation often notice emotional precipitants for discrete episodes
or atrial fibrillation although a recent study showed that the only reliable precipitant
was alcohol use (2). There were significant limitations with that study with
attrition and length of the study although I generally agree that alcohol is a
clear participant. Precipitants need to
be carefully approached and I suspect that attentive physicians have noted variable
phenomenology on an individual basis.
The high hazard ratio for opioids is a little puzzling.
Hyperadrenergic states can occur with the euphorigenic effects and withdrawal
effects as well. Direct comparison with stimulants may be difficult due to
rapid dose escalation and some degree of tachyphylaxis. Cannabis is not surprising to me at all. Many
initial cannabis smokers notice that their heart is pounding and don’t know
why. They find it unexpected given the conventional
wisdom that cannabis is supposed to be a benign substance. Many initial users
also get increased anxiety and, in some cases, have a panic attack that may be
due to the cardiac sensations. The primary heart pounding sensation is because
cannabis causes hypotension and they are experiencing reflex tachycardia. The
effects may be less predictable because cannabis use can affect both
sympathetic and parasympathetic pathways that can potentiate arrhythmias. A
case report of cannabis induced atrial flutter (3) was described as occurring
in a woman with a history of hypertension that eventually had to be terminated
by an intravenous antiarrhythmic.
Atrial fibrillation and other cardiac arrhythmias are
another good reason for avoiding intoxicants including alcohol (in the supplementary analysis alcohol had a Hazard Ratio of 2.37). It could be argued that it is basically a
numbers game – since most people who use these intoxicants do not develop
incident atrial fibrillation. As of this
moment, even if you have had your DNA analyzed for what are known about atrial
fibrillation genes – you can’t be certain that you are not susceptible to
the problem. And as outlined above there are many additional cardiac problems
and that are possible from using these compounds. The safest path is to avoid these intoxicants
all together.
George Dawson, MD, DFAPA
References:
1: Lin AL, Nah G,
Tang JJ, Vittinghoff E, Dewland TA, Marcus GM. Cannabis, cocaine,
methamphetamine, and opiates increase the risk of incident atrial fibrillation.
Eur Heart J. 2022 Oct 18:ehac558. doi: 10.1093/eurheartj/ehac558. Epub ahead of
print. PMID: 36257330.
2: Marcus GM, Modrow MF, Schmid CH, Sigona K, Nah G, Yang
J, Chu TC, Joyce S, Gettabecha S, Ogomori K, Yang V, Butcher X, Hills MT,
McCall D, Sciarappa K, Sim I, Pletcher MJ, Olgin JE. Individualized Studies of
Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical
Trial. JAMA Cardiol. 2022 Feb 1;7(2):167-174. doi: 10.1001/jamacardio.2021.5010.
PMID: 34775507; PMCID: PMC8591553.
3: Fisher BA, Ghuran A, Vadamalai V, Antonios TF.
Cardiovascular complications induced by cannabis smoking: a case report and
review of the literature. Emerg Med J. 2005 Sep;22(9):679-80. doi:
10.1136/emj.2004.014969. PMID: 16113206; PMCID: PMC1726916. [full text]
