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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 2  |  Issue : 2  |  Page : 232-238

Multiple mechanisms of cocaine-induced Brugada electrocardiogram pattern


1 Department of Cardiology, St. Luke's University Health Network, Bethlehem, PA 18020, USA
2 Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA

Date of Submission12-Jun-2016
Date of Acceptance27-Jul-2016
Date of Web Publication28-Dec-2016

Correspondence Address:
Sudip Nanda
Department of Internal Medicine, St. Luke's University Hospital Network, 801, Ostrum Street, Bethlehem, Pennsylvania 18015
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2455-5568.196877

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  Abstract 


Cocaine is the most commonly used illicit drug with life-threatening cardiovascular complications, including coronary syndrome, sudden cardiac death, hypertensive crisis, aortic dissection, and stroke. Brugada pattern is a known complication of cocaine intoxication. There are, however, multiple mechanisms that can precipitate the Brugada pattern, beyond the sodium channel-blocking effect of cocaine. The various modes by which cocaine can cause Brugada pattern are discussed. Our patient presented with Brugada pattern and coronary vasospasm, both of which completely resolved with nitroglycerin. This case confirms that vasospasm of the right coronary artery can present as Brugada pattern.
The following core competencies are addressed in this article: Medical knowledge, patient care.

Keywords: Brugada, chest pain, cocaine, vasospasm


How to cite this article:
Manda Y, Stone LE, Singh A, Agrawal S, Shirani J, Nanda S. Multiple mechanisms of cocaine-induced Brugada electrocardiogram pattern. Int J Acad Med 2016;2:232-8

How to cite this URL:
Manda Y, Stone LE, Singh A, Agrawal S, Shirani J, Nanda S. Multiple mechanisms of cocaine-induced Brugada electrocardiogram pattern. Int J Acad Med [serial online] 2016 [cited 2022 Jan 19];2:232-8. Available from: https://www.ijam-web.org/text.asp?2016/2/2/232/196877




  Introduction Top


Brugada pattern is known to have multifaceted causes, some congenital and some exogenously induced. While much research has been conducted on the genetic predispositions that underlie the congenital manifestations, there is significant clinical value in unwinding the mechanisms of inducible Brugada pattern. In particular, certain illicit drugs seem to be connected to transient Brugada manifestation – specifically cocaine. We review the clinical relevance of a cocaine-Brugada connection in the context of a case report, seguing into a discussion of the electrochemical actions of cocaine and their proposed influence on cardiac conduction. We then propose possible treatment routes in view of this mechanistic discussion.


  Case Report Top


A 40-year-old female with history of hypertension, asthma, and cocaine use presented to the Emergency Department with 3 h of intermittent chest pain radiating to the left shoulder. She had a temperature of 97.9°F, pulse rate of 78/min, respiratory rate of 16/min, and blood pressure of 104/59 mmHg. Her clinical examination was normal. Electrocardiogram (ECG) on arrival showed sinus rhythm with nonspecific ST-T wave changes and initial troponin-I concentration was 0.37 ng/dL (normal <0.04 ng/dL). She developed recurrent chest pain in the emergency department and repeat ECG demonstrated 2 mm downsloping ST-segment elevation in leads V1 and V2 associated with nonspecific T wave changes (Panel A). These changes were suggestive of acute coronary syndrome with ST-segment elevation in the precordial leads. Although type 1 Brugada pattern ECG can have a similar appearance, the patient was taken for emergent coronary angiography due to ongoing chest pain.

The angiography revealed normal left main and left circumflex arteries and a 30% stenosis of the proximal left anterior descending artery with smooth edges. The dominant right coronary artery (RCA) had long segments of critical smooth narrowing with tapering edges, suggestive of coronary vasospasm (Panel B) with involvement of the proximal RCA-ostium and the conus branch (Panel B - white arrow). Her angiography was complicated by an episode of ventricular fibrillation (VF) that was successfully defibrillated using a single biphasic shock at 200 J. Multiple doses of intracoronary nitroglycerin (total 800 µg) resulted in complete resolution of coronary vasospasm of the RCA and conus branch (Panel C). Repeat ECG revealed normalization of ST segment changes (Panel D). These ECG changes suggest an unmasking Brugada type 1 pattern, induced by cocaine-triggering coronary vasospasm. The patient was treated with long-acting calcium channel blockers and sustained full cocaine abstinence. At 2 years of follow-up, she continued to be asymptomatic. This patient's presenting and resolved ECG and angiogram are provided in [Figure 1].
Figure 1: Panel A - Electrocardiogram demonstrating ST elevation suggestive of Brugada pattern with ongoing chest pain. Panel B - Coronary angiogram of right coronary artery demonstrating coronary vasospasm with demonstrable spasm of ostium and of conus branch (white arrow). Panel C - Resolution of coronary vasospasm of right coronary artery and conus branch (white arrow) after administration of intracoronary nitroglycerin. Panel D - Repeat electrocardiogram demonstrating resolution of the Brugada pattern

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  Discussion Top


Cocaine is an alkaloid derived from the leaves of the Erythroxylum coca plant. Once processed, it produces a colorless, bitter tasting powder with an oral bioavailability of 33% and nasal bioavailability of 19%. It is metabolized by pseudocholinesterase in the blood as well as the cytochrome pathway in the liver. A varying amount is excreted unchanged in the urine.[1]

Cocaine use can lead to life-threatening cardiovascular complications, including coronary syndrome, sudden cardiac death, hypertensive crisis, aortic dissection, and stroke. Three of the numerous ways by which cocaine exerts significant effect on the cardiovascular system are relevant to our discussion.

Local effect on cardiovascular and associated tissue-block sodium channels

One of the genetic abnormalities causing Brugada syndrome is a loss-of-function mutation of the sodium channel. Cocaine has well-defined sodium channel-blocking effect that leads to its local anesthetic properties.

Central effect on brain sympathetic centers: Inhibits norepinephrine reuptake

This action on norepinephrine is particularly prominent in peripheral nerve terminals, increasing the amount of neurotransmitter available in the synaptic cleft. Vongpatanasin et al. studied how this effect manifests in organ systems, particularly the heart, finding that indeed the cardiovascular system demonstrates reduced norepinephrine uptake in the presence of cocaine. However, the heart's response might be dependent on the mode of cocaine's introduction. While intranasal administration causes predictable coronary vasospasms, cocaine infused directly into the coronary arteries has been shown to produce minimal changes in arterial tone.[3]

Effect on autonomic centers: Induces hyperthermia

Death during cocaine-induced hyperthermia can occur at 10–20 times lower blood levels than the lethal dose.[4] Hyperthermia occurs due to a combination of impaired sweating, diminished cutaneous vasodilation, and a hypermetabolic state. In addition, heat perception in the central nervous system is also impaired such that patient does not feel as much discomfort even though the core temperature is elevated. Concerning cardiac dysfunction, it is quite well known that some mutant sodium channels have temperature-dependent variation in function.[5] Hyperthermia-induced channel dysfunction, which may be caused by cocaine intake, might then precipitate the Brugada pattern.

In 1992, Brugada syndrome was described as a cause of sudden cardiac death, with typical ECG patterns of ST-segment elevation in the right precordial leads. Originally, three variants, Types 1, 2, and 3, were described, depending on the morphology of ST segment. Type I had a coved ST-segment elevation ≥2 mm, negative T wave, with little or no isoelectric separation between the two. Type 2 had ST-segment elevation, a positive or biphasic T wave in saddleback configuration. Type 3 had ST segment elevation ≤1 mm with a T wave that is either coved or saddleback. [Figure 2]a and [Figure 2]b shows labeled ECG of Brugada Types 1 and 2, respectively.[6]
Figure 2: (a) Trademark characteristics of Brugada Pattern Type 1 electrocardiogram. RBBB = Right Bundle Branch Block. (b) Trademark characteristics of Brugada Pattern Type 2 electrocardiogram. New consensus standards combined previous classifications of “Type 2” and “Type 3.” BBB = Bundle Branch Block

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In 2013, the Heart Rhythm Society published two consensus criteria for the diagnosis of Brugada syndrome:

  1. Type 1 ST segment morphology, ≥2 mm, in at least one right-sided leads (V1, V2) in standard or superior intercostal space (2nd, 3rd, or 4th), occurring spontaneously or provoked by a class I antiarrhythmic drug
  2. Type 2 or Type 3 ST segment elevation in at least one right-sided lead in standard or superior intercostal space, when provocative testing with intravenous class I antiarrhythmic drug induces Type 1 morphology.[7]


Brugada syndrome was originally linked to a variant of SCN5A, a gene coding for a sodium channel in the heart's electrical system.[8] Since then, additional research has revealed a number of mutations that are also capable of inducing Brugada syndrome. [Table 1][9] shows complete list of identified mutations.
Table 1: Genetic channel abnormalities associated with Brugada syndrome

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The Brugada pattern of ECG abnormalities is prevalent in a large number of clinical conditions other than Brugada syndrome. Class 1 anti-arrhythmic and antianginals induce a Brugada pattern through their specific mechanism of action on the heart's electrical system. Cardiac-specific conditions, including left ventricular hypertrophy, right bundle branch block, and pulmonary embolism, can also induce Brugada pattern. While each of these listed cardiac conditions has its own characteristic ECG finding, its pathology can also result in the characteristic ST-segment change mimicking a Brugada diagnosis. Non-cardiac conditions can cause a Brugada pattern as a secondary symptom, including Friedreich's ataxia, hyperkalemia, and pectus excavatum.[9] [Table 2][10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23] shows a list of drugs, cardiac conditions, and non-cardiac conditions that can induce Brugada pattern.
Table 2: Brugada pattern causing drugs and conditions

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Despite advances in identifying risk factors for Brugada syndrome, the specific mechanism responsible for the syndrome remains hypothetical. The best hypotheses currently describe changes in the heart's electrical patterns, thus termed the depolarization hypothesis and the repolarization hypothesis. One theory supporting these hypotheses suggests that decreased conduction in the right ventricular outflow tract (RVOT) causes an elevated ST segment, visualizable in the right precordial leads of the patient's ECG.

The second theory concerns the mechanistic behavior of the electrical channels in the myocardium. It is hypothesized that changes seen in a Brugada ECG are the result of an imbalance between the inward and outward currents generated by INa and, respectively. Theoretically, a-loss-of function mutation in INa channels, a contributor to the phase 0 upshoot of the cardiac action potential, will cause the membrane potential to favor an outward current due to the strong presence of channels. This disequilibrium, predominant in the epicardium, will subsequently shorten the duration of the cardiac action potential. In the endocardium, however, where conductance is less powerful, there is less effect on the resulting action potential.[9] [Figure 3] shows visual representation of the relationship between channel conductance and the cardiac action potential.
Figure 3: Cardiac action potential related to the conductance of INa, INa-L, and Ito. INaand Ito function nearly reciprocally during phases 0/1 of the action potential

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Our patient provided the opportunity to observe a classic Brugada pattern in the presence of RCA spasm, with complete resolution of pattern occurring with vasospasm cessation. Cocaine was present throughout the patient's system hence resolution of sodium channel blockade was not expected. Our patient was also not hyperthermic. Thus, of the three different mechanisms by which cocaine can cause Brugada pattern, vessel spasm was the most likely cause in our patient. As evidenced by the angiogram, there was significant ischemia in the right ventricle and RVOT. Ischemia affects depolarization and repolarization of the tissue involved, resulting in the Brugada pattern. In addition, it is currently well known that calcium and potassium channels are affected during ischemia. Brugada syndrome has been described with abnormalities of calcium and potassium channels, and these may be the cause of the ST segment changes in predisposed individuals.[24] [Table 1] shows a list of known Brugada syndrome-producing electrical channel mutations.

Managing a patient with a demonstrated Brugada pattern requires extra vigilance and forethought from a medical team. It is currently well known that patients with Brugada-type ECGs secondary to medications, electrolytes, or fevers are at high risk of subsequent arrhythmias.[25] This factor must be taken into account when assessing a patient's ability to tolerate other medical innervations. Anesthetics such as lidocaine, bupivacaine, and propofol are known to precipitate sudden cardiac death in these patients.[26] The mechanism by which propofol causes Brugada pattern is not known. Considering the increased use of propofol as an anesthetic in almost all invasive procedures and its ability to produce the so-called “propofol infusion syndrome,” a combination of metabolic acidosis, hyperkalemia, rhabdomyolysis, and ultimately cardiac arrest-care is to be entertained in all cases with Brugada type pattern where using such anesthetic is necessary.[25],[27]

Our patient is doing well at 2 years of follow-up. She follows of routine course of vasodilators while abstaining from cocaine. An alert has also been placed in her chart to avoid the use of propofol during subsequent procedures.


  Conclusion Top


We discussed the various mechanisms by which cocaine can produce Brugada pattern. In particular, with pertinence to our patient, RCA spasm induced by cocaine caused Brugada pattern. She was not hyperthermic, and cocaine was still in her system when the Brugada pattern resolved with resolution of coronary artery spasm. For long-term management, it is preferable to avoid the use of propofol, bupivacaine, and lidocaine in susceptible patients.

Treatment of ventricular tachycardia/VF (VT/VF) in such patients represents a dilemma. If vasospasm is causing the VT/VF, nitroglycerine and relief of spasm is curative. If it is the sodium channel-blocking effect of cocaine that unmasked a Brugada pattern, it mimics the provoked effect of another sodium channel blocker procainamide. Quinidine is the preferred treatment of VT/VF in Brugada syndrome and may be the preferred treatment in that situation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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2.
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Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV, Nesterenko VV, et al. Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res 1999;85:803-9.  Back to cited text no. 5
    
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Noda T, Shimizu W, Taguchi A, Satomi K, Suyama K, Kurita T, et al. ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome. J Am Coll Cardiol 2002;40:1841-7.  Back to cited text no. 24
    
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Vernooy K, Delhaas T, Cremer OL, Di Diego JM, Oliva A, Timmermans C, et al. Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome. Heart Rhythm 2006;3:131-7.  Back to cited text no. 27
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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