**2. Cocaine**

This "white powder," extracted from coca leaves, is not only one of the oldest known stimulants but also the most known cardiotoxic illicit drug.

Several cases and series of sudden death, in the hours following cocaine consumption, were reported. The main likely cause is cocaine-induced arrhythmia [3].

> To manage this wide QRS tachycardia related to sodium channel blockade, general measures should rapidly be initiated. Oxygenation and ventilation should be optimized, and rapid cooling should be initiated when extreme hyperthermia is present. Sedation with a benzodiazepine is indicated to control behavior, to lower heart rate which may be sufficient to improve conduction and for its antianginal effects in patients with cocaine-associated acute

> **Figure 1.** ECG performed after a wide QRS tachycardia cardioversion showing a complete right bundle branch block in

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This electrocardiographic manifestation, occurring in case of acute intoxication and mediated by pH decrease, is reversed by hypertonic sodium bicarbonate [8, 12, 13]. In case of persistence of this tachycardia with abnormal QRS prolongation, antiarrhythmic drugs should be administrated. Class IA and class IC antiarrhythmic drugs are classically contraindicated as they may potentiate QRS enlargement via a synergistic action on sodium channels. In contrast, lidocaine (class IB) can compete with cocaine for binding to the sodium channel, and it has a rapid offset responsible for the decrease in QRS duration. However, it was suggested that lidocaine exacerbated cocaine-associated seizures and arrhythmias as a result of similar effects on sodium channels [14]. Beta-blockers are contraindicated in case of cocaine intoxication as they exacerbate coronary vasospasm resulting in an increased risk of myocardial infarction [11]. No data exist concerning the efficacy of amiodarone in clinical cocaine intoxi-

Moreover, a classic Brugada pattern has been noted in cocaine users, as seen with class IA antiarrhythmic drugs [15, 16]. It is quite likely that these patients express a sodium channel mutation described in association with Brugada abnormality and that the sodium channel blocking properties of cocaine made the patients' underlying physiological abnormality more evident [4]. Recently, El Mazloum et al. reported four cases of out-of-hospital cardiac arrest

after acute cocaine intoxication associated with Brugada ECG patterns [17].

coronary syndrome [4, 11].

a 38-year-old man with 10 years use of cocaine.

cation [11].

• Brugada-like pattern

Four mechanisms are implicated in the genesis of arrhythmia in case of cocaine intoxication: sodium channel blockade, potassium channel blockade, catecholamine excess, and finally myocardial infarction (MI) and myocarditis [4]. Recently, sinus bradycardia has been described as a result of chronic cocaine use [5–7] that may be related to a cocaine-induced desensitization of beta-adrenergic receptors [6].

The main measure for patients suffering from cocaine-induced arrhythmia is withholding the drug and referring to a detoxification center to prevent recurrent events. In addition, specific strategies should also be conducted according to the type of arrhythmia.

#### **2.1. Sodium channel blockade**

• Wide QRS tachycardia related to sodium channel blockade and reentry ventricular tachycardia

First, the blockade of fast inward sodium channels by cocaine is well described as a class IC effect according to the Vaughan-Williams classification of antiarrhythmic agents. Modulators of the effect of cocaine are increased in heart rate and decreased in pH which increases the degree of sodium channel blockade [8].

Electrocardiographic (ECG) manifestations mimic those of other sodium channel blockers, drugs and toxins, as tricyclic antidepressants. These manifestations depend on the degree of intoxication. In fact, early and minimal toxicity results in the impairment of conduction on the right side leading to a rightward axis deviation and QRS duration prolongation, and then, as toxicity increases, a right bundle branch block (RBBB) appears in the precordial leads (**Figure 1**). This pattern associated with sinus tachycardia, often shown in case of cocaine intoxication, may be confused with a true ventricular tachycardia resulting from a reentry or focal mechanism that can also complicate cocaine intoxication as reported in many series [4, 9, 10].

**Figure 1.** ECG performed after a wide QRS tachycardia cardioversion showing a complete right bundle branch block in a 38-year-old man with 10 years use of cocaine.

To manage this wide QRS tachycardia related to sodium channel blockade, general measures should rapidly be initiated. Oxygenation and ventilation should be optimized, and rapid cooling should be initiated when extreme hyperthermia is present. Sedation with a benzodiazepine is indicated to control behavior, to lower heart rate which may be sufficient to improve conduction and for its antianginal effects in patients with cocaine-associated acute coronary syndrome [4, 11].

This electrocardiographic manifestation, occurring in case of acute intoxication and mediated by pH decrease, is reversed by hypertonic sodium bicarbonate [8, 12, 13]. In case of persistence of this tachycardia with abnormal QRS prolongation, antiarrhythmic drugs should be administrated. Class IA and class IC antiarrhythmic drugs are classically contraindicated as they may potentiate QRS enlargement via a synergistic action on sodium channels. In contrast, lidocaine (class IB) can compete with cocaine for binding to the sodium channel, and it has a rapid offset responsible for the decrease in QRS duration. However, it was suggested that lidocaine exacerbated cocaine-associated seizures and arrhythmias as a result of similar effects on sodium channels [14]. Beta-blockers are contraindicated in case of cocaine intoxication as they exacerbate coronary vasospasm resulting in an increased risk of myocardial infarction [11]. No data exist concerning the efficacy of amiodarone in clinical cocaine intoxication [11].

• Brugada-like pattern

mainly acute coronary syndromes and rhythm disturbances resulting in more and more

Most of the researches have focused on mental health effects and neurotoxicity of illicit drugs. Some of them were interested to cardiovascular dangers in general, and they were almost cases or series reports. The current review will focus on the topic of cardiac arrhythmias secondary to drug abuse in which we will explain their different mechanisms and principles of

This "white powder," extracted from coca leaves, is not only one of the oldest known stimu-

Several cases and series of sudden death, in the hours following cocaine consumption, were

Four mechanisms are implicated in the genesis of arrhythmia in case of cocaine intoxication: sodium channel blockade, potassium channel blockade, catecholamine excess, and finally myocardial infarction (MI) and myocarditis [4]. Recently, sinus bradycardia has been described as a result of chronic cocaine use [5–7] that may be related to a cocaine-induced

The main measure for patients suffering from cocaine-induced arrhythmia is withholding the drug and referring to a detoxification center to prevent recurrent events. In addition, specific

• Wide QRS tachycardia related to sodium channel blockade and reentry ventricular

First, the blockade of fast inward sodium channels by cocaine is well described as a class IC effect according to the Vaughan-Williams classification of antiarrhythmic agents. Modulators of the effect of cocaine are increased in heart rate and decreased in pH which increases the

Electrocardiographic (ECG) manifestations mimic those of other sodium channel blockers, drugs and toxins, as tricyclic antidepressants. These manifestations depend on the degree of intoxication. In fact, early and minimal toxicity results in the impairment of conduction on the right side leading to a rightward axis deviation and QRS duration prolongation, and then, as toxicity increases, a right bundle branch block (RBBB) appears in the precordial leads (**Figure 1**). This pattern associated with sinus tachycardia, often shown in case of cocaine intoxication, may be confused with a true ventricular tachycardia resulting from a reentry or focal mechanism

that can also complicate cocaine intoxication as reported in many series [4, 9, 10].

reported young's sudden cardiac deaths [3].

lants but also the most known cardiotoxic illicit drug.

desensitization of beta-adrenergic receptors [6].

**2.1. Sodium channel blockade**

degree of sodium channel blockade [8].

tachycardia

reported. The main likely cause is cocaine-induced arrhythmia [3].

strategies should also be conducted according to the type of arrhythmia.

management.

178 Cardiac Arrhythmias

**2. Cocaine**

Moreover, a classic Brugada pattern has been noted in cocaine users, as seen with class IA antiarrhythmic drugs [15, 16]. It is quite likely that these patients express a sodium channel mutation described in association with Brugada abnormality and that the sodium channel blocking properties of cocaine made the patients' underlying physiological abnormality more evident [4]. Recently, El Mazloum et al. reported four cases of out-of-hospital cardiac arrest after acute cocaine intoxication associated with Brugada ECG patterns [17].

Cocaine abuse should be stopped. Mostly, ECG reverts toward normal as toxicity resolves [13]. Otherwise, sudden cardiac death risk should be evaluated, and implantable cardioverter defibrillator should be discussed in coordination with cardiac electrophysiologists.

#### **2.2. Potassium channel blockade**

Cocaine is known to block the rectifying potassium channels resulting in QT interval prolongation and hyperpolarization leading to early and late afterdepolarizations. If an afterdepolarization of significant magnitude occurs at a time when a critical number of cells can conduct an impulse, an ectopic beat can trigger a reentrant rhythm, and monomorphic ventricular tachycardia or torsades de pointes (TdP) occur [18–21].

Management of TdP and QT prolongation resulting from cocaine-associated potassium channel blockade is similar to those from other causes. In fact, for QT prolongation, electrolytic abnormalities, mainly hypokalemia and hypomagnesaemia, should be identified and rapidly corrected. Prophylactic magnesium is also suggested in patients with QT interval above 500 ms [4]. In case of TdP, magnesium, potassium replacement, and even overdrive are the main treatments. QT prolonging drugs should be withheld [4, 22].

When a cocaine-associated acute myocardial infarction is diagnosed, classical antithrombotic therapies should be administrated according to current guidelines, and primary PCI should be rapidly performed. Moreover, benzodiazepine should be initiated, and β-blockers have to

**Figure 2.** Cardiac magnetic resonance imaging revealing a late gadolinium enhancement (LGE) of the subepicardial layers of the septal and lateral walls of the left ventricle in a cocaine abuse man admitted for a ventricular tachycardia

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For scar-related reentry, as well as focal, ventricular tachycardia, management is based on classical measures and therapies according to current guidelines [34] with respect of the above-cited particularities and contraindications related to cocaine intoxication. In addition, implantable cardioverter defibrillator implantation should be deferred until the resolution of

Besides these therapies, radiofrequency ablation using 3D mapping was described to be an effective therapy in 86% of drug refractory ventricular tachycardia related to cocaine

Recent reports have demonstrated that chronic cocaine use is a strong predictor of sinus bradycardia compared with a matched group of nonusers and resulted in three- to sevenfold increased risk of sinus bradycardia [5–7]. Despite the presence of sinus bradycardia, all

Sharma et al. have showed also that current cocaine dependence corresponds to an increased

Common physiological manifestations of cocaine are related to its adrenergic effects. However, with chronic exposure to cocaine, Franklin et al. have postulated that the mechanism of sinus bradycardia may be related to a cocaine-induced desensitization of beta-adrenergic receptors. A blockage of the fast sodium current reduces sinus node automaticity, and results in brady-

be avoided because of the risk of further vasospasm [11, 33].

**2.5. Sinus bradycardia and early repolarization pattern**

patients were able to augment their sinus rate with activity [6].

odd of demonstrating early repolarization by a factor of 4.92 [5].

the acute episode [32, 34].

cardia have also been evocated [6].

use [10].

management.

#### **2.3. Catecholamine excess**

The common acute effect of cocaine is to block the presynaptic uptake of dopamine, norepinephrine, and epinephrine, resulting in an augmented level of these neurotransmitters at the postsynaptic terminal, producing an exaggerated catecholamine effect [23–25].

This produces sinus tachycardia, a very common finding in these patients, reentrant supraventricular tachycardia [26], and atrial fibrillation, noted in case and series reports [27].

Supportive care is generally sufficient to control sinus tachycardia. Sedation with benzodiazepine, oxygen, cooling, and volume resuscitation are the main measures. For reentrant supraventricular tachycardia, the use of a calcium channel blocker is often required. Finally, atrial fibrillation should be classically treated, using short-acting drugs as rhythm is generally controlled when toxicity resolves and avoiding β-blockers and class IA and IC antiarrhythmic drugs [4].

#### **2.4. Myocardial infarction and myocarditis**

The risk of myocardial infarction is multiplied by 24 within the next hour following cocaine consumption [28]. Cocaine-associated myocardial ischemia and infarction is a multifactorial process that results from increased demand, vasospasm, enhanced coagulation, impaired thrombolysis, and accelerated atherogenesis [29]. A catecholamine excess (trigger) induced by cocaine on such a vulnerable myocardium (substrate) may provoke the development of ventricular arrhythmias and sudden cardiac death.

In addition to myocardial infarction, scar-related macroreentrant ventricular tachycardia may also complicate cocaine-induced acute toxic myocarditis (**Figure 2**) as demonstrated in several case and series reports [30–32].

**Figure 2.** Cardiac magnetic resonance imaging revealing a late gadolinium enhancement (LGE) of the subepicardial layers of the septal and lateral walls of the left ventricle in a cocaine abuse man admitted for a ventricular tachycardia management.

When a cocaine-associated acute myocardial infarction is diagnosed, classical antithrombotic therapies should be administrated according to current guidelines, and primary PCI should be rapidly performed. Moreover, benzodiazepine should be initiated, and β-blockers have to be avoided because of the risk of further vasospasm [11, 33].

For scar-related reentry, as well as focal, ventricular tachycardia, management is based on classical measures and therapies according to current guidelines [34] with respect of the above-cited particularities and contraindications related to cocaine intoxication. In addition, implantable cardioverter defibrillator implantation should be deferred until the resolution of the acute episode [32, 34].

Besides these therapies, radiofrequency ablation using 3D mapping was described to be an effective therapy in 86% of drug refractory ventricular tachycardia related to cocaine use [10].

#### **2.5. Sinus bradycardia and early repolarization pattern**

Cocaine abuse should be stopped. Mostly, ECG reverts toward normal as toxicity resolves [13]. Otherwise, sudden cardiac death risk should be evaluated, and implantable cardioverter

Cocaine is known to block the rectifying potassium channels resulting in QT interval prolongation and hyperpolarization leading to early and late afterdepolarizations. If an afterdepolarization of significant magnitude occurs at a time when a critical number of cells can conduct an impulse, an ectopic beat can trigger a reentrant rhythm, and monomorphic ven-

Management of TdP and QT prolongation resulting from cocaine-associated potassium channel blockade is similar to those from other causes. In fact, for QT prolongation, electrolytic abnormalities, mainly hypokalemia and hypomagnesaemia, should be identified and rapidly corrected. Prophylactic magnesium is also suggested in patients with QT interval above 500 ms [4]. In case of TdP, magnesium, potassium replacement, and even overdrive are the

The common acute effect of cocaine is to block the presynaptic uptake of dopamine, norepinephrine, and epinephrine, resulting in an augmented level of these neurotransmitters at the

This produces sinus tachycardia, a very common finding in these patients, reentrant supraventricular tachycardia [26], and atrial fibrillation, noted in case and series reports [27].

Supportive care is generally sufficient to control sinus tachycardia. Sedation with benzodiazepine, oxygen, cooling, and volume resuscitation are the main measures. For reentrant supraventricular tachycardia, the use of a calcium channel blocker is often required. Finally, atrial fibrillation should be classically treated, using short-acting drugs as rhythm is generally controlled when

The risk of myocardial infarction is multiplied by 24 within the next hour following cocaine consumption [28]. Cocaine-associated myocardial ischemia and infarction is a multifactorial process that results from increased demand, vasospasm, enhanced coagulation, impaired thrombolysis, and accelerated atherogenesis [29]. A catecholamine excess (trigger) induced by cocaine on such a vulnerable myocardium (substrate) may provoke the development of

In addition to myocardial infarction, scar-related macroreentrant ventricular tachycardia may also complicate cocaine-induced acute toxic myocarditis (**Figure 2**) as demonstrated in several

toxicity resolves and avoiding β-blockers and class IA and IC antiarrhythmic drugs [4].

postsynaptic terminal, producing an exaggerated catecholamine effect [23–25].

defibrillator should be discussed in coordination with cardiac electrophysiologists.

tricular tachycardia or torsades de pointes (TdP) occur [18–21].

main treatments. QT prolonging drugs should be withheld [4, 22].

**2.2. Potassium channel blockade**

180 Cardiac Arrhythmias

**2.3. Catecholamine excess**

**2.4. Myocardial infarction and myocarditis**

ventricular arrhythmias and sudden cardiac death.

case and series reports [30–32].

Recent reports have demonstrated that chronic cocaine use is a strong predictor of sinus bradycardia compared with a matched group of nonusers and resulted in three- to sevenfold increased risk of sinus bradycardia [5–7]. Despite the presence of sinus bradycardia, all patients were able to augment their sinus rate with activity [6].

Sharma et al. have showed also that current cocaine dependence corresponds to an increased odd of demonstrating early repolarization by a factor of 4.92 [5].

Common physiological manifestations of cocaine are related to its adrenergic effects. However, with chronic exposure to cocaine, Franklin et al. have postulated that the mechanism of sinus bradycardia may be related to a cocaine-induced desensitization of beta-adrenergic receptors.

A blockage of the fast sodium current reduces sinus node automaticity, and results in bradycardia have also been evocated [6].
