https://orcid.org/0000-0002-0913-3497
Abstract
Ventricular electrical storm (VES) is a clinical scenario characterized by the clustering of multiple episodes of sustained ventricular arrhythmias (VA) over a short duration. Patients with VES are prone to psychological disorders, heart failure decompensation, and increased mortality. Studies have shown that 10–28% of the patients with secondary prevention ICDs can sustain VES. The triad of a susceptible electrophysiologic substrate, triggers, and autonomic dysregulation govern the pathogenesis of VES. The rate of VA, underlying ventricular function, and the presence of implantable cardioverter-defibrillator (ICD) determine the clinical presentation. A multi-faceted approach is often required for management consisting of acute hemodynamic stabilization, ICD reprogramming when appropriate, antiarrhythmic drug therapy, and sedation. Some patients may be eligible for catheter ablation, and autonomic modulation with thoracic epidural anesthesia, stellate ganglion block, or cardiac sympathetic denervation. Hemodynamically unstable patients may benefit from the use of left ventricular assist devices, and extracorporeal membrane oxygenation. Special scenarios such as idiopathic ventricular fibrillation, Brugada syndrome, Long and short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis have been described as well. VES is a cardiac emergency that requires swift intervention. It is associated with poor short and long-term outcomes. A structured team-based management approach is paramount for the safe and effective treatment of this sick cohort.
Introduction
Ventricular electrical storm (VES) is a clinical scenario characterized by the clustering of multiple episodes of sustained ventricular arrhythmias (VAs) over a short duration. Several definitions of VES have been proposed over the years (Supplementary material online, Table S1), but the most widely accepted one is three or more episodes of sustained VA occurring within 24 h, requiring either anti-tachycardia pacing (ATP) or implantable cardioverter-defibrillators (ICDs) shocks, with each event separated by at least 5 min.1–5 In patients without ICDs, VES is typified by three or more discrete occurrences of sustained VA.1,6
Patients with VES are prone to psychological disorders, heart failure decompensation, and increased mortality.7,8 The management of VES is genuinely multidisciplinary, including but not limited to: thorough clinical evaluation, resuscitation skills, critical care management with sedation, ICD reprogramming, medical therapies, ablation, and sympathetic modulation procedures.9,10 Not surprisingly, VES has a tremendous impact on healthcare resources. Prompt recognition of VES and implementation of rapid treatment can be the difference between life and death. With this comprehensive review, we attempt to provide an up-to-date contemporary understanding and management of VES.
Epidemiology
Ventricular electrical storm is incompletely understood from large trials studying ventricular tachycardia (VT) ablation. This is because patients with VES either form a small proportion of enrollees or are excluded from most of the prominent VT studies.11 Furthermore, depending on the defining criteria, the incidence may vary among different reports. Male sex, advanced age, lower left ventricular (LV) ejection fraction, and the presence of medical comorbidities increase the susceptibility of developing VES.11 Ventricular electrical storm prevalence in ischaemic cardiomyopathy (ICM) and non-ischaemic dilated cardiomyopathy (NICM) is roughly estimated to be comparable with high recurrence rates in both subsets.8,11,12 Studies have shown that 10–28% of the patients with secondary prevention ICDs can sustain VES3,13,14 with over a three-fold increase in mortality as compared to controls.8 Monomorphic VT as a triggering arrhythmia, was found to have a higher association with VES as compared to polymorphic VT and ventricular fibrillation (VF).8,15 (Supplementary material online, Table S1) summarizes the clinical trials of VES. The mean frequency of VES was 2–55 episodes. Prior treatment with Vaughan Williams class I antiarrhythmic drugs is associated with a higher incidence of VES.8,11
Pathophysiology
Patients with structural heart disease, predictably form the bulk of the cases of VES. However, individuals with structurally normal hearts can also be predisposed to VES owing to genetic arrhythmia syndromes such as catecholaminergic polymorphic VT (CPVT), Brugada syndrome, long QT syndrome (LQTS).16–18 The term VES is quite apt in a way that it mandates a perfect storm of several factors. Ventricular electrical storm is governed by a complex interplay of the following elements (Figure 1):
Presence of a susceptible electrophysiologic substrate: In ICM, NICM or other forms of cardiomyopathy, scarred myocardium provides the anatomical basis for re-entrant VA.19
Triggers: Inciting factors may include ischaemia, decompensated heart failure, infections, endocrine emergencies, electrolyte derangements, and antiarrhythmic drug non-compliance.20 At the cellular level, calcium mishandling and disorders of protein phosphorylation have also been proposed as potential mechanisms for arrhythmia-induced cardiomyopathy.21–23 While addressing a reversible aetiology is the prudent approach, per prior studies, a reversible cause cannot be determined in the majority of cases.24
Autonomic dysregulation: Certain chronic cardiac conditions may portend a neural remodelling, which involves a decrease in parasympathetic input, and eventual sympathetic hyperinnervation.25 A temporal increase in sympathetic activity may drive the initiation of the arrhythmic episode. Furthermore, ICD shocks increase the adrenergic tone, creating a vicious cycle that may lead to VES.
Additionally, genetic arrhythmia syndromes may provide the necessary substrate for VES, even in the absence of structural heart disease.26 Fascinatingly, causative genes of genetic conditions such as Brugada syndrome, and early repolarization have been discovered in patients developing VES from other causes such as ischaemia. This association begs the intriguing question: Is VES just a phenotypic culmination of several disease processes, or is it a separate entity by itself? The answer remains elusive.
The triad of ventricular electrical storm consists of a complex interplay between an arrhythmogenic substrate, autonomic imbalances, and acute triggers. Some examples of each are enlisted in this figure.
Clinical presentations and diagnosis
Ventricular electrical storm can have diverse clinical presentations, depending on multiple factors. The rate of VA, underlying LV function, and the presence of ICD determine how patients present. Patients with significant LV dysfunction usually are unable to tolerate VES and may present with syncope and sudden cardiac death as the first symptom. Patients who are relatively more compensated, especially those with slower VA, may present with symptoms of palpitations, and lightheadedness before developing syncope. Patients with incessant VA with slower rates (100–120 beats/min), may also develop symptoms representative of worsening congestive heart failure.27
Individuals with ICDs can have a wide range of presentations—from being completely asymptomatic with VA episodes treated with ATP to recurrent ICD shocks.28 Patients with frequent ICD shocks are at risk for developing psychological disorders, particularly severe anxiety, and depression.29
Prompt identification of VES is critical as it warrants rapid management. The approach depends on whether or not the patient has an ICD implanted. In those patients without an ICD, the clinician must scrutinize the twelve-lead electrocardiogram of the presenting rhythm. The majority of VES present with monomorphic VT, which is a re-entrant arrhythmia generated by non-homogenous myocardial scarring. Polymorphic VT and VF, on the other hand, are seen in acute ischaemia, electrolytes disarrangement, prolonged QT intervals, and genetic channelopathies. Often times, differentiating monomorphic VT vs. supraventricular tachycardia (SVT) with aberrancy can be challenging.30 Several algorithms have been published to aid in the differential of VT from SVT.31–33 In cases of ambiguity, especially in the setting of structural heart disease, a wide-complex tachycardia should be treated as VA unless proved otherwise.34,35 If the situation permits, an astute clinician should make a mental checklist to rule-out the following conditions in all wide complex tachycardias:
SVT with a pre-existing bundle branch block: Thus, comparison to a prior electrocardiogram is paramount.
SVT with rate-related aberrant conduction: Right bundle branch aberrancy more common but can present with left bundle branch block as well.36
Antidromic atrioventricular reciprocating tachycardia: By extension, any SVT that conducts antegrade over an accessory pathway can produce a wide QRS complex. Pre-excitation with a delta wave can be recognized by careful review of QRS morphology.
Electrolyte disorders such as hyperkalaemia.
Drugs: The list predominantly includes sodium channel blockers such as the Vaughan Williams Class I antiarrhythmic drugs (Quinidine, Procainamide, Flecainide, among others). If time permits, a thorough history should be obtained to exclude the use of recreational drugs such as cocaine and amphetamines that can have similar QRS complex widening effects.
Paced rhythms: Certain specific causes such as pacemaker-mediated tachycardia, and normal upper-rate behaviour must be considered in patients with ICDs.
In patients with ICDs who experience device therapies, the first step must be to verify if the therapies were indeed appropriate. Shocks for reasons other than VA are termed inappropriate shocks and can occur in as high as 40% of ICD recipients despite novel discriminating device algorithms.37–39 Some of the established reasons for inappropriate therapies include SVT with rates in the VT/VF zone, oversensing in the ventricular lead: such as T-wave oversensing and lead malfunction with noise detection associated with lead fracture, or loss of lead insulation.37,40
Management
Initial assessment
It is imperative to determine haemodynamic instability if present on initial evaluation. In cases of haemodynamic decompensation, resources and personnel should be immediately diverted to execute advanced cardiac life support with effective cardiopulmonary resuscitation.5,41 Patients without a pulse and rhythm consistent with VA, should be emergently defibrillated.42
Simultaneously, a systems check must be run to identify any reversible causes of VES. Electrolyte disorders must be rapidly corrected with particular attention to hypokalaemia and hypomagnesemia.43–45 The cardiac catheterization lab must be alerted if acute ischaemia is suspected as an aetiology. Decompensated heart failure, hypoxia, and lack of adherence to antiarrhythmic drugs must be identified swiftly. Certain unique scenarios might call for specific management, which will be addressed in a separate section to follow. Patients with pre-existing systemic comorbidities or acute end-organ damage must be triaged to critical care units, preferably a cardiac intensive care unit.15,28
Device evaluation and reprogramming
Verification of the appropriateness of ICD therapies is the first step. In cases where inappropriate therapies are detected, turning off ICD shock therapy should precede any other intervention.46 In situations when access to device programmers is limited, a magnet placed on the ICD can serve to deactivate tachycardia therapies. Inappropriate shocks generate a hyperadrenergic state, which in turn can precipitate VES by itself.47 Even when treatments are appropriate, if the patient is haemodynamically stable, consideration must be given to temporarily deactivate shock therapies. For re-entrant monomorphic VT, programming longer detection times, and enhancing ATP therapies should be attempted.1,48–50Anti-tachycardia pacing has been proven to be safe and effective when compared to shocks, and most importantly, cause much less patient discomfort.51,52
Sometimes, device pacing algorithms can prove to be proarrhythmic. Examples include algorithms to minimize ventricular pacing, where device-generated pauses and short-long-short sequences can lead to VA.53,54 Furthermore, LV pacing as seen in cardiac resynchronization therapy (CRT) can result in triggered VA with premature ventricular complexes (PVCs), or re-entrant VA by promoting heterogeneous conduction.55 If it is established that CRT was recently programmed and was a potential source of proarrhythmia, then disabling LV pacing can potentially mitigate the storm episode.
Medical therapies
Antiarrhythmic medications are the backbone of VES management (Table 1). Rapid administration of antiarrhythmics is required as part of initial resuscitative measures.5,41 Studies have demonstrated that antiarrhythmic drugs can assist in significantly reducing VES recurrence, albeit without impacting mortality.56
Summary of drugs used for ventricular electrical storm describing the mechanism of action, dosing strategies, pharmokinetics, monitoring parameters, and key adverse effects
| Vaughan Williams class | Drug | Channels affected | Dose | Half-life | Metabolism | Specific use | Monitoring | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| IA | Quinidine | INa, IKr, Ito, M, alpha | Quinidine sulfate: 200–600 mg PO q6–12 h; quinidine gluconate 324–648 mg PO q8 h; IV loading dose 800 mg/50 mL, maintenance 50 mg/min | 6–8 h | Predominant hepatic | VT/VF (Brugada syndrome, short QT syndrome) | Prolongs QTc, QRS; use with caution in HF, G6PD deficiency increases DFT | Diarrhoea, gastritis, VA, TdP, AVB, blood dyscrasias dizziness, headache (Cinchonism) |
| Procainamide | INa, IKr | IV: bolus 10 mg/kg over 20 min, maintenance 2–3 g/24 h; oral: 500–1250 mg q6 h | 2–5 h | Hepatic and renal (NAPA) | ACS; pre-excited AF mimicking VT/VF | Prolongs QTc, QRS. NAPA levels; increases DFT | TdP, AVB, HF exacerbation, Lupus-like syndrome | |
| 1B | Lidocaine | INa | IV: bolus 1–1.5 mg/kg, can repeat up to total of 3 mg/kg, maintenance: 1–4 mg/min | 7–30 min | Hepatic | Ischaemic VT/VF | Check Lidocaine levels; QTc can shorten | Delirium, psychosis, seizures, tinnitus, bradycardia, AVB, sinus arrest |
| Mexiletine | INa | 150–300 mg PO q8–12 h | 10–14 h | Hepatic metabolism via CYP2D6. Renal excretion | VT/VF; helpful in LQTS3 | QTc can shorten | Tremors, ataxia, HF, AVB | |
| II | Propranolol | Non-selective β-blocker | IV: 1–3 mg q5 min to a maximum of 5 mg; PO: 10–40 mg q6 h immediate release; 60–160 mg q12 h extended release | 3–6 h (immediate release) | Extensive first-pass effect; hepatic metabolism via CYP2D6 | VT/PVC; LQTS | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, nightmares, dizziness |
| Nadolol | Non-selective β-blocker | 40–320 mg daily | 20–24 h | Not metabolized. Excreted unchanged in the urine | VT/PVC; LQTS; CPVT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, dizziness, cold extremities | |
| Metoprolol | β1-receptor | IV: 5 mg q5 min up to 3 doses; PO: metoprolol tartarate 25–100 mg q12 h | 3–4 h | Hepatic metabolism | VT, PVC | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, fatigue, depression, diarrhoea | |
| Esmolol | β1-receptor | IV: bolus: 0.5 mg/kg, maintenance: 0.05 mg/kg/min | 9 min | Metabolized by RBC esterases | VT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, dizziness, nausea | |
| III | Sotalol | IKr; β1,2 | IV: 7 5 mg q12 h; PO: 80–160 mg q12 h | 12 h | Renal | VT, VF, PVC | Prolongs QTc (monitor on initiation), slows SA node; increase AV node refractoriness; decreases DFT | TdP, bradycardia, hypotension, AVB, fatigue, depression, diarrhoea |
| Amiodarone | INa, ICa, IKr, IK1, IKs, Ito, Beta receptors, Alpha receptor, nuclear T3 receptor | IV: bolus 300 mg for VF/pulseless VT arrest; 150 mg for stable VT; maintenance: 1 mg/min × 6 h, then 0.5 mg/min × 18 h; PO: 400 mg × q 8–12 h for 7–14 days, then 200–400 mg daily | 4–14 weeks | Hepatic | VT, VF, PVC | Prolongs QTc, QRS, slows SA node; increase AV node refractoriness; increases DFT | Hypotension, bradycardia, AVB, TdP, corneal microdeposits, thyroid abnormalities, nausea, constipation, photosensitivity, skin discolouration, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis, or pneumonitis | |
| IV | Verapamil | ICa | IV: 2.5–5 mg q 15–30 min; PO: sustained release 240–480 mg/day | 3–7 h | Fascicular VT, RVOT VT | Slows SA node; increase AV node refractoriness | Hypotension, AVB, bradycardia, exacerbation of HFrEF, oedema, headache, rash, gingival hyperplasia, constipation |
| Vaughan Williams class | Drug | Channels affected | Dose | Half-life | Metabolism | Specific use | Monitoring | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| IA | Quinidine | INa, IKr, Ito, M, alpha | Quinidine sulfate: 200–600 mg PO q6–12 h; quinidine gluconate 324–648 mg PO q8 h; IV loading dose 800 mg/50 mL, maintenance 50 mg/min | 6–8 h | Predominant hepatic | VT/VF (Brugada syndrome, short QT syndrome) | Prolongs QTc, QRS; use with caution in HF, G6PD deficiency increases DFT | Diarrhoea, gastritis, VA, TdP, AVB, blood dyscrasias dizziness, headache (Cinchonism) |
| Procainamide | INa, IKr | IV: bolus 10 mg/kg over 20 min, maintenance 2–3 g/24 h; oral: 500–1250 mg q6 h | 2–5 h | Hepatic and renal (NAPA) | ACS; pre-excited AF mimicking VT/VF | Prolongs QTc, QRS. NAPA levels; increases DFT | TdP, AVB, HF exacerbation, Lupus-like syndrome | |
| 1B | Lidocaine | INa | IV: bolus 1–1.5 mg/kg, can repeat up to total of 3 mg/kg, maintenance: 1–4 mg/min | 7–30 min | Hepatic | Ischaemic VT/VF | Check Lidocaine levels; QTc can shorten | Delirium, psychosis, seizures, tinnitus, bradycardia, AVB, sinus arrest |
| Mexiletine | INa | 150–300 mg PO q8–12 h | 10–14 h | Hepatic metabolism via CYP2D6. Renal excretion | VT/VF; helpful in LQTS3 | QTc can shorten | Tremors, ataxia, HF, AVB | |
| II | Propranolol | Non-selective β-blocker | IV: 1–3 mg q5 min to a maximum of 5 mg; PO: 10–40 mg q6 h immediate release; 60–160 mg q12 h extended release | 3–6 h (immediate release) | Extensive first-pass effect; hepatic metabolism via CYP2D6 | VT/PVC; LQTS | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, nightmares, dizziness |
| Nadolol | Non-selective β-blocker | 40–320 mg daily | 20–24 h | Not metabolized. Excreted unchanged in the urine | VT/PVC; LQTS; CPVT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, dizziness, cold extremities | |
| Metoprolol | β1-receptor | IV: 5 mg q5 min up to 3 doses; PO: metoprolol tartarate 25–100 mg q12 h | 3–4 h | Hepatic metabolism | VT, PVC | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, fatigue, depression, diarrhoea | |
| Esmolol | β1-receptor | IV: bolus: 0.5 mg/kg, maintenance: 0.05 mg/kg/min | 9 min | Metabolized by RBC esterases | VT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, dizziness, nausea | |
| III | Sotalol | IKr; β1,2 | IV: 7 5 mg q12 h; PO: 80–160 mg q12 h | 12 h | Renal | VT, VF, PVC | Prolongs QTc (monitor on initiation), slows SA node; increase AV node refractoriness; decreases DFT | TdP, bradycardia, hypotension, AVB, fatigue, depression, diarrhoea |
| Amiodarone | INa, ICa, IKr, IK1, IKs, Ito, Beta receptors, Alpha receptor, nuclear T3 receptor | IV: bolus 300 mg for VF/pulseless VT arrest; 150 mg for stable VT; maintenance: 1 mg/min × 6 h, then 0.5 mg/min × 18 h; PO: 400 mg × q 8–12 h for 7–14 days, then 200–400 mg daily | 4–14 weeks | Hepatic | VT, VF, PVC | Prolongs QTc, QRS, slows SA node; increase AV node refractoriness; increases DFT | Hypotension, bradycardia, AVB, TdP, corneal microdeposits, thyroid abnormalities, nausea, constipation, photosensitivity, skin discolouration, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis, or pneumonitis | |
| IV | Verapamil | ICa | IV: 2.5–5 mg q 15–30 min; PO: sustained release 240–480 mg/day | 3–7 h | Fascicular VT, RVOT VT | Slows SA node; increase AV node refractoriness | Hypotension, AVB, bradycardia, exacerbation of HFrEF, oedema, headache, rash, gingival hyperplasia, constipation |
Alpha, alpha-adrenergic receptor; AV, atrioventricular; AVB, atrioventricular block; Beta, beta-adrenergic receptor; CPVT, catecholaminergic polymorphic ventricular tachycardia; DFT, defibrillation threshold; h, hours; HF, heart failure; HFrEF, HF with reduced ejection fraction; Ica, L-type calcium channel current; IK1, inward rectifier potassium channel; IKr, rapid delayed rectifier potassium current; IKs, slow delayed rectifier potassium current; INa, fast inward sodium current; Ito, transient outward potassium current; IV, intravenous; LQTS, long QT syndrome; min, minutes; NAPA, n-acetyl procainamide; PO, per oral; PVC, premature ventricular complex; QTc, corrected QT interval; RVOT, right ventricular outflow tract; T3, triiodothyronine; TdP, torsades de pointes; VF, ventricular fibrillation; VT, ventricular tachycardia.
Summary of drugs used for ventricular electrical storm describing the mechanism of action, dosing strategies, pharmokinetics, monitoring parameters, and key adverse effects
| Vaughan Williams class | Drug | Channels affected | Dose | Half-life | Metabolism | Specific use | Monitoring | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| IA | Quinidine | INa, IKr, Ito, M, alpha | Quinidine sulfate: 200–600 mg PO q6–12 h; quinidine gluconate 324–648 mg PO q8 h; IV loading dose 800 mg/50 mL, maintenance 50 mg/min | 6–8 h | Predominant hepatic | VT/VF (Brugada syndrome, short QT syndrome) | Prolongs QTc, QRS; use with caution in HF, G6PD deficiency increases DFT | Diarrhoea, gastritis, VA, TdP, AVB, blood dyscrasias dizziness, headache (Cinchonism) |
| Procainamide | INa, IKr | IV: bolus 10 mg/kg over 20 min, maintenance 2–3 g/24 h; oral: 500–1250 mg q6 h | 2–5 h | Hepatic and renal (NAPA) | ACS; pre-excited AF mimicking VT/VF | Prolongs QTc, QRS. NAPA levels; increases DFT | TdP, AVB, HF exacerbation, Lupus-like syndrome | |
| 1B | Lidocaine | INa | IV: bolus 1–1.5 mg/kg, can repeat up to total of 3 mg/kg, maintenance: 1–4 mg/min | 7–30 min | Hepatic | Ischaemic VT/VF | Check Lidocaine levels; QTc can shorten | Delirium, psychosis, seizures, tinnitus, bradycardia, AVB, sinus arrest |
| Mexiletine | INa | 150–300 mg PO q8–12 h | 10–14 h | Hepatic metabolism via CYP2D6. Renal excretion | VT/VF; helpful in LQTS3 | QTc can shorten | Tremors, ataxia, HF, AVB | |
| II | Propranolol | Non-selective β-blocker | IV: 1–3 mg q5 min to a maximum of 5 mg; PO: 10–40 mg q6 h immediate release; 60–160 mg q12 h extended release | 3–6 h (immediate release) | Extensive first-pass effect; hepatic metabolism via CYP2D6 | VT/PVC; LQTS | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, nightmares, dizziness |
| Nadolol | Non-selective β-blocker | 40–320 mg daily | 20–24 h | Not metabolized. Excreted unchanged in the urine | VT/PVC; LQTS; CPVT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, dizziness, cold extremities | |
| Metoprolol | β1-receptor | IV: 5 mg q5 min up to 3 doses; PO: metoprolol tartarate 25–100 mg q12 h | 3–4 h | Hepatic metabolism | VT, PVC | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, fatigue, depression, diarrhoea | |
| Esmolol | β1-receptor | IV: bolus: 0.5 mg/kg, maintenance: 0.05 mg/kg/min | 9 min | Metabolized by RBC esterases | VT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, dizziness, nausea | |
| III | Sotalol | IKr; β1,2 | IV: 7 5 mg q12 h; PO: 80–160 mg q12 h | 12 h | Renal | VT, VF, PVC | Prolongs QTc (monitor on initiation), slows SA node; increase AV node refractoriness; decreases DFT | TdP, bradycardia, hypotension, AVB, fatigue, depression, diarrhoea |
| Amiodarone | INa, ICa, IKr, IK1, IKs, Ito, Beta receptors, Alpha receptor, nuclear T3 receptor | IV: bolus 300 mg for VF/pulseless VT arrest; 150 mg for stable VT; maintenance: 1 mg/min × 6 h, then 0.5 mg/min × 18 h; PO: 400 mg × q 8–12 h for 7–14 days, then 200–400 mg daily | 4–14 weeks | Hepatic | VT, VF, PVC | Prolongs QTc, QRS, slows SA node; increase AV node refractoriness; increases DFT | Hypotension, bradycardia, AVB, TdP, corneal microdeposits, thyroid abnormalities, nausea, constipation, photosensitivity, skin discolouration, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis, or pneumonitis | |
| IV | Verapamil | ICa | IV: 2.5–5 mg q 15–30 min; PO: sustained release 240–480 mg/day | 3–7 h | Fascicular VT, RVOT VT | Slows SA node; increase AV node refractoriness | Hypotension, AVB, bradycardia, exacerbation of HFrEF, oedema, headache, rash, gingival hyperplasia, constipation |
| Vaughan Williams class | Drug | Channels affected | Dose | Half-life | Metabolism | Specific use | Monitoring | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| IA | Quinidine | INa, IKr, Ito, M, alpha | Quinidine sulfate: 200–600 mg PO q6–12 h; quinidine gluconate 324–648 mg PO q8 h; IV loading dose 800 mg/50 mL, maintenance 50 mg/min | 6–8 h | Predominant hepatic | VT/VF (Brugada syndrome, short QT syndrome) | Prolongs QTc, QRS; use with caution in HF, G6PD deficiency increases DFT | Diarrhoea, gastritis, VA, TdP, AVB, blood dyscrasias dizziness, headache (Cinchonism) |
| Procainamide | INa, IKr | IV: bolus 10 mg/kg over 20 min, maintenance 2–3 g/24 h; oral: 500–1250 mg q6 h | 2–5 h | Hepatic and renal (NAPA) | ACS; pre-excited AF mimicking VT/VF | Prolongs QTc, QRS. NAPA levels; increases DFT | TdP, AVB, HF exacerbation, Lupus-like syndrome | |
| 1B | Lidocaine | INa | IV: bolus 1–1.5 mg/kg, can repeat up to total of 3 mg/kg, maintenance: 1–4 mg/min | 7–30 min | Hepatic | Ischaemic VT/VF | Check Lidocaine levels; QTc can shorten | Delirium, psychosis, seizures, tinnitus, bradycardia, AVB, sinus arrest |
| Mexiletine | INa | 150–300 mg PO q8–12 h | 10–14 h | Hepatic metabolism via CYP2D6. Renal excretion | VT/VF; helpful in LQTS3 | QTc can shorten | Tremors, ataxia, HF, AVB | |
| II | Propranolol | Non-selective β-blocker | IV: 1–3 mg q5 min to a maximum of 5 mg; PO: 10–40 mg q6 h immediate release; 60–160 mg q12 h extended release | 3–6 h (immediate release) | Extensive first-pass effect; hepatic metabolism via CYP2D6 | VT/PVC; LQTS | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, nightmares, dizziness |
| Nadolol | Non-selective β-blocker | 40–320 mg daily | 20–24 h | Not metabolized. Excreted unchanged in the urine | VT/PVC; LQTS; CPVT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, bronchospasm, dizziness, cold extremities | |
| Metoprolol | β1-receptor | IV: 5 mg q5 min up to 3 doses; PO: metoprolol tartarate 25–100 mg q12 h | 3–4 h | Hepatic metabolism | VT, PVC | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, fatigue, depression, diarrhoea | |
| Esmolol | β1-receptor | IV: bolus: 0.5 mg/kg, maintenance: 0.05 mg/kg/min | 9 min | Metabolized by RBC esterases | VT | Slows SA node; increase AV node refractoriness | Bradycardia, hypotension, AVB, dizziness, nausea | |
| III | Sotalol | IKr; β1,2 | IV: 7 5 mg q12 h; PO: 80–160 mg q12 h | 12 h | Renal | VT, VF, PVC | Prolongs QTc (monitor on initiation), slows SA node; increase AV node refractoriness; decreases DFT | TdP, bradycardia, hypotension, AVB, fatigue, depression, diarrhoea |
| Amiodarone | INa, ICa, IKr, IK1, IKs, Ito, Beta receptors, Alpha receptor, nuclear T3 receptor | IV: bolus 300 mg for VF/pulseless VT arrest; 150 mg for stable VT; maintenance: 1 mg/min × 6 h, then 0.5 mg/min × 18 h; PO: 400 mg × q 8–12 h for 7–14 days, then 200–400 mg daily | 4–14 weeks | Hepatic | VT, VF, PVC | Prolongs QTc, QRS, slows SA node; increase AV node refractoriness; increases DFT | Hypotension, bradycardia, AVB, TdP, corneal microdeposits, thyroid abnormalities, nausea, constipation, photosensitivity, skin discolouration, peripheral neuropathy, tremor, hepatitis, cirrhosis, pulmonary fibrosis, or pneumonitis | |
| IV | Verapamil | ICa | IV: 2.5–5 mg q 15–30 min; PO: sustained release 240–480 mg/day | 3–7 h | Fascicular VT, RVOT VT | Slows SA node; increase AV node refractoriness | Hypotension, AVB, bradycardia, exacerbation of HFrEF, oedema, headache, rash, gingival hyperplasia, constipation |
Alpha, alpha-adrenergic receptor; AV, atrioventricular; AVB, atrioventricular block; Beta, beta-adrenergic receptor; CPVT, catecholaminergic polymorphic ventricular tachycardia; DFT, defibrillation threshold; h, hours; HF, heart failure; HFrEF, HF with reduced ejection fraction; Ica, L-type calcium channel current; IK1, inward rectifier potassium channel; IKr, rapid delayed rectifier potassium current; IKs, slow delayed rectifier potassium current; INa, fast inward sodium current; Ito, transient outward potassium current; IV, intravenous; LQTS, long QT syndrome; min, minutes; NAPA, n-acetyl procainamide; PO, per oral; PVC, premature ventricular complex; QTc, corrected QT interval; RVOT, right ventricular outflow tract; T3, triiodothyronine; TdP, torsades de pointes; VF, ventricular fibrillation; VT, ventricular tachycardia.
Beta-blockers: The surge in adrenaline is a robust mechanistic consideration in VES episodes. Hence, the application of β-blockers to blunt the sympathetic nervous system makes intuitive sense. Due to a rapid onset of action and short half-life, esmolol can be used as an intravenous infusion in the acute setting.57 In patients with VA after a recent myocardial infarction, β-blockers can decrease VA recurrence.58,59Non-selective β-blockers such as propranolol are preferred over metoprolol or bisoprolol.34,60,61 The superiority of propranolol over metoprolol could be secondary to a higher central nervous system concentration owing to its lipophilic nature. A recent article described the use of amiodarone with propranolol vs. metoprolol in acute VES management.62 In this study, Chatzidou et al.62 reported earlier termination of VA in the propranolol arm along with less time in intensive care and fewer recurrences of VA. Caution must be exercised when using β-blockers in patients with decompensated heart failure, as that may precipitate cardiogenic shock.63
Amiodarone: Amiodarone is placed under class III in the Vaughan Williams classification, which consists of potassium-channel blockers. However, amiodarone is genuinely a mixed bag such that it can block sodium channels, and can also function as a β-blocker and a calcium channel blocker.64 Amiodarone has a slow onset of action, and the half-life ranges around 6–8 weeks. Thus, a loading dose is recommended at the outset (1–1.5 g/day in divided doses). Notably, in the acute setting, amiodarone exerts its action predominantly by the β-blocker component (h), and the rest of the channels take longer to block (days to weeks).65 Owing to its multi-channel blocking properties, amiodarone is one of the most effective initial drugs administered in VES.5,66 For out-of-hospital cardiac arrests due to VA, Amiodarone has shown a higher survival to hospital admission as compared to Lidocaine.67,68 However, more recent trials by Kudenchuk et al.69 have failed to reproduce this effect. Santangeli et al.56 in a recent meta-analysis have suggested that treatment with amiodarone may result in increased mortality in patients with ICDs. The long-term use of amiodarone is fraught with side effects, thus impacting its use. The adverse effects include corneal deposits in the majority of users, photosensitivity in 25–75% patients, elevated liver enzymes in up to 30% patients, hepatitis/cirrhosis <3%, pulmonary fibrosis in less than a fifth of the patients, thyroid gland derangements, skin pigmentation, among others.66
Sotalol: Sotalol formulations consist of the L- and D-enantiomers. The D-isomer is a potassium channel blocker only, and L-isomer has an additional non-selective β-blocker effect. D-sotalol has been shown to increase mortality when studied in randomized controlled trials in patients with systolic heart failure, and prior acute myocardial infarctions.70 Sotalol has been demonstrated to have superiority over lidocaine in the acute termination of VA calling for its mention in the guidelines.5,71 Based on the optical pharmacological therapy in cardioverter-defibrillator patients (OPTIC) trial, sotalol was reported to reduce ICD shocks.72 However, amiodarone and β-blockers were shown to be more effective in preventing ICD shocks as compared to sotalol alone.72
Lidocaine and Mexiletine: Lidocaine is a Class IB antiarrhythmic agent that exerts its action by sodium channel blockade.73 Lidocaine preferentially works in ischaemic myocardium, promoting its administration in VA occurring during/after acute myocardial infarctions.10,74 The efficacy of Lidocaine in terminating VA in non-ischaemic VT has been reported to be 8–30%; thus, it is less commonly used as solo therapy in these scenarios.34 Another drug with a similar pharmacologic profile is Mexiletine. Mexiletine is given orally and is often used in conjunction with class III AAD to enhance VA control.
Procainamide and Quinidine: Procainamide is a Class IA agent which is a potent sodium channel blocker.73 Procainamide is a two-in-one drug as its metabolite, N-acetyl procainamide, works as a potassium channel blocker. Another property that makes procainamide unique is its cardiac ganglion blocking function, which can be useful in curbing resistant arrhythmias.75 Procainamide has been demonstrated to be superior to amiodarone and lidocaine in separate studies.76,77 Gastrointestinal discomfort can be quite common, but caution must be exercised to detect lupus-like syndrome which may occur with chronic therapy.10,56 Quinidine is another Class IA agent which can be used for VES, with particular efficacy in patients with Brugada syndrome, early repolarization syndrome, and short QT syndrome.5
Sedation
When VES remains intractable despite aggressive anti-arrhythmic therapies, deep sedation, along with mechanical ventilation, must be considered. The goal is to alleviate the sympathetic overdrive by achieving Richmond Agitation-Sedation Scale values below −2.78 Preference is given to opioid analgesics and benzodiazepines over propofol owing to lesser negative inotropic effects.79,80 Sedation, in addition to directly suppressing arrhythmogenesis, also serves by buying time for the critical care team to identify and target reversible causes, if any. Our group has previously demonstrated in a study of 65 patients with VA and severe cardiomyopathy that VA and skin sympathetic nerve activity can be suppressed effectively by general anaesthesia.81
Catheter ablation
The predominant presenting arrhythmia in VES is monomorphic VT, which is potentiated by heterogeneous myocardial scar.19 Catheter ablation (CA) works by homogenizing the myocardial scar, thus potentially limiting re-entrant circuits.10 CA finds a role in patients who have refractory VT despite medications or have adverse effects from the drugs (Supplementary material online, Table S2).5 A meta-analysis by Nayyar et al.82 meticulously analysed 39 publications and reported that after more than a year of follow-up, there was 83% survival, and 60% freedom from VA recurrence. CA has since been established to be superior to medical therapy based on multiple trials in terms of VA recurrence and ICD shocks.10,56,83,84 Randomized trials are yet to show a mortality benefit of CA in VES, that some retrospective studies have described.10,11 However, in patients with polymorphic VT or focally triggered VF storm after a myocardial infarct, CA of the triggers has shown to decrease VA recurrences and improve mortality.85 With regard to the timing of CA, Frankel et al.86 have demonstrated that early referral for CA for VT results in better 1-year VT-free survival.
While CA has established a strong foothold in the management of VA in ICM, the same cannot be said about NICM due to the relative paucity of data.87 A prospective trial of 227 patients based in Germany, demonstrated short-term success in NICM; however, long-term outcomes were worse compared to ICM.88 More recently, 267 patients with NICM were compared with 196 patients with ICM by Muser et al.,87 and they reported that CA of VES in both groups had similar VA recurrence and mortality outcomes. The electrophysiologist must have a lower threshold of mapping and ablating in the epicardium for NICM, given the nature of scar distribution in certain disease conditions.83,87 Shirai et al.89 have described that non-scar Purkinje fibre VTs can be seen in about 5% of patients with structural heart disease undergoing VT ablation, and thus a predominant substrate-based ablation may not be sufficient in such cases.
In patients where the traditional endocardial and epicardial CA have failed to prevent VA recurrences, novel alternative technologies have emerged.90 When VT circuits are deemed to be deep intramural, strategies such as half-normal saline irrigation91 and bipolar ablation, have been described.92 Retrograde coronary venous ethanol infusion has been suggested for refractory VT, particularly those arising from the LV summit.93 Needle ablation has surfaced as another promising option for refractory intramural VT where a 27-gauge needle can be inserted into the tissue for deep energy delivery.94
Autonomic modulation
Curtailing the adrenergic surge can be a critical weapon when VES is refractory to aggressive antiarrhythmic drugs and sedation strategies.25,95 Autonomic modulation has been described to treat VES in prior studies.96–99 Multiple techniques of autonomic modulation exist with the most popular ones being thoracic epidural anaesthesia (TEA), percutaneous stellate ganglion block (SGB), thoracoscopic, or open cardiac sympathetic denervation (CSD).15 Autonomic modulation has been used for LQTS and CPVT associated VA for many years.17,100 In the last few years, the application of neuraxial modulation has been described in patients with structural heart disease.98
Injection of a local anaesthetic agent such as bupivacaine into the thoracic epidural space constitutes TEA. In most circumstances, TEA serves as a temporizing measure, to control VES, until more definitive treatment strategies are executed.99Figure 2 depicts the TEA procedure. An epidural catheter is advanced into the epidural space beyond a Touhy needle and secured in place. Lack of blood or cerebrospinal fluid aspiration is used to exclude intravascular or intrathecal catheter placement. At the initiation of TEA, a 1‐mL injection of bupivacaine is administered via the epidural catheter, followed by an infusion at 2 mL/h of bupivacaine. The dose can be titrated according to the arrhythmic response. Thoracic epidural anaesthesia, while temporary, has shown promising efficacy in acute suppression of VES.99,101
Illustration describing thoracic epidural anaesthesia. A Tuohy needle is used to gain access to the epidural space. An epidural catheter is advanced beyond the Touhy needle and secured in place. Lack of blood or cerebrospinal fluid aspiration is used to exclude intravascular or intrathecal catheter placement. At the initiation of thoracic epidural anaesthesia, a 1-mL injection of bupivacaine is administered via the epidural catheter, followed by an infusion at 2 mL/h of bupivacaine. The dose can be titrated according to the arrhythmic response.
Stellate ganglion block is similar but involves the injection of local anaesthetic into the left or bilateral stellate ganglia.98 Stellate ganglion block can be quickly performed at the bedside using ultrasound guidance in our centre. In the largest series of 30 patients with VES undergoing urgent SGB, At 24 h, 60% of patients were free of VA. in those with frequent ICD therapies, VA episodes were significantly reduced by 92% from 26 ± 41 to 2 ± 4 in the 72 h after SGB.95Figure 3A–C illustrates ultrasound-guided SGB. The stellate ganglion is located behind the carotid artery. A 22-gauge, 2-inch spinal needle (PAJUNK®) is used and advanced in-plane in a posterior-to-anterior direction to the anterior surface of the longus coli muscle to avoid all vascular structures. A 7 mL of bupivacaine is injected after a negative aspiration.95
Illustration describing the anatomy and landmarks for stellate ganglion block. (A) The classic approach is shown. The cricoid cartilage is palpated, and the vascular bundle is displaced laterally, and the needle tip is inserted perpendicular to the skin. (B) The cross-section at the level of the C6 with the classical approach on the left of the figure, and the ultrasound-guided approach on the right is shown. Note that in the ultrasound-guided approach, the needle course is lateral and inferior to the vascular bundle. (C) Image of stellate ganglion blockade guided by ultrasonography. The red arrow shows the path of the needle. CA, carotid artery; IJ, internal jugular vein; LC, longus colli muscle; SCM, sternocleidomastoid; SG, area of stellate ganglion; TH, thyroid; VB, vertebral.
Left CSD involves thoracoscopic or open surgical removal of the lower half of the left stellate ganglia and the T2-4 thoracic ganglia (Figure 4).97,102 Cardiac sympathetic denervation has been shown to reduce ICD shocks significantly in patients with resistant VES, with bilateral CSD having a slight edge over left CSD.96 Cardiac sympathetic denervation might be more effective in rapid VT, partially attributing to elevated sympathetic output, while it is less effective in patients with scar driven slow VT.103 Cardiac sympathetic denervation is useful in some patients with idiopathic VF or polymorphic VT when other measures have failed.104 In a prospectively enrolled 17 patients with LQTS and high risk of sudden death who underwent left cardiac sympathetic denervation, the mean left arm skin nerve activity decreased significantly, possibly reflecting reduced sympathetic tone. These patients had no ventricular arrhythmic event at 1-year follow-up.105
Illustration describing thoracoscopic cardiac sympathetic denervation. Two to three small incisions are made over the left chest along the mid-axillary line. A camera is used to provide a magnified vision of the surgical field. (A) The visualization of thoracic ganglia after tissue dissection is shown. (B and C) The pleura being incised with an electrocautery hook dissector to access the sympathetic chain are shown. (D) Reflects the removal of T-4 thoracic ganglia to complete the cardiac sympathetic denervation. Note that the stellage ganglion has not been excised to avoid iatrogenic Horner’s syndrome.
Haemodynamic support during ventricular electrical storm
Institution of mechanical haemodynamic support should be considered early in the management of haemodynamically unstable arrhythmias when conventional therapy fails (Figure 5). Extracorporeal membrane oxygenation (ECMO) is a form of heart-lung bypass that can be used to support VES patients for days or weeks until the vulnerable myocardial substrate settles down. ECMO or other mechanical supporting systems are especially useful in weaning catecholamine infusions after cardiac surgery or intervention and help terminate catecholamine-driven electrical storm while restoring systemic circulation.106 In a meta-analysis including 2465 adult and 82 paediatric patients, a substantial mortality benefit was observed among high-risk patients, as identified with PAINESD risk score or suffering from electrical storm and treated with prophylactic mechanical circulatory support.107
Flowchart depicting the proposed algorithm for the management of ventricular electrical storm. ACLS, advanced cardiac life support; ATP, anti-tachycardia pacing; Balloon pump, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenation; ICD, implantable cardioverter-defibrillator; LCSD, left cardiac sympathetic denervation; Long-QT, long-QT syndrome; LVAF, left ventricular assist device; MMVT, monomorphic VT; PMVT, polymorphic VT; SGB, stellate ganglion blockade; TEA, thoracic epidural anaesthesia; VA, ventricular arrhythmia; VES, ventricular electrical storm; VF, ventricular fibrillation; VT, ventricular tachycardia.
Performing CA in patients with VES and underlying cardiomyopathy comes with the expected risks of haemodynamic decompensation.87 Baratto et al.106 studied 64 patients with haemodynamically unstable VTs undergoing CA and demonstrated that prophylactic use of ECMO, allowed safe procedural completion in 92% of the patients, with non-inducibility of VT in 69%, and almost 90% survival at a median follow-up of 21 months. Mathuria et al.108 studied a cohort of 93 patients with structural heart disease undergoing CA for VT and reported improved survival with prophylactic use of percutaneous LV assist device, as opposed to rescue use.
Special scenarios
There are certain unique situations where specific treatment strategies have to be followed. Herein, we describe some salient points about a few special conditions. This is not meant to be an in-depth review of these entities.
Idiopathic VT/VF: In structurally normal hearts, the triggering PVCs are most commonly mapped to the outflow tracts, Purkinje system, or the papillary muscles (left ventricle or right ventricle).109 The mechanism of outflow tract VT is most frequently delayed after-depolarization, and can respond to iv adenosine or verapamil. Fascicular VT or Belhassen VT are classically known to be verapamil-sensitive.110Long-term ablation outcomes are excellent.111
Brugada syndrome: The medical management of Brugada syndrome includes IV isoproterenol. Owing to its ability to block the transient outward potassium current (Ito current), quinidine can prove efficacious in the long-term treatment of Brugada syndrome. Cilostazole has been shown to be useful in managing refractory VF in Brugada syndrome with early repolarization syndrome.112 Epicardial right ventricular outflow tract substrate modification has been proved to be very effective for VA associated with Brugada syndrome.113
Long QT syndrome: Specific lifestyle measures and trigger-avoidance depends on the subtype of LQTS. β-blockers and flecainide form the mainstay of medical management, and if there are VA recurrences, then left, or bilateral CSD can be considered.100,114 Intentional atrial pacing have been shown as an adjunctive strategy to stabilize the QT interval and reduce VA episodes.115
Short QT syndrome: Quinidine is the only antiarrhythmic drug of proven efficacy in short QT syndrome. Atrial fibrillation is a frequent accompaniment, and rhythm-control with propafenone has been studied to be beneficial.116
Early repolarization syndrome: Certain patients with early repolarization syndrome can develop VF. Quinidine and isoproterenol have been shown to be beneficial in this population.117
Catecholaminergic polymorphic VT: Similar to LQTS, β-blockers, and flecainide are the first-line treatment options, with CSD as the option for refractory cases.
Arrhythmogenic right ventricular cardiomyopathy (ARVC): For patients with ARVC, avoidance of exercise is critical in preventing VES. For refractory VES, CA has been proven to be efficacious. However, patients tend to suffer from chronic heart failure symptoms, that may progress despite arrhythmia mitigation.118
Cardiac sarcoidosis: VT ablation in patients with cardiac sarcoidosis can be challenging. Several VT morphologies may be identified, and mapping of both ventricles is often needed (Figure 6). A third of patients may be epicardial ablation.119
Procedural details from an extensive ablation performed in a patient with non-ischaemic cardiomyopathy due to cardiac sarcoidosis presenting with electrical storm. Patient had four prior failed ablations for ventricular tachycardia including a septal needle ablation and had breakthrough episodes despite lidocaine, amiodarone, quinidine, and mexiletine and a stellate ganglion block. (A) The clinical VT which had left bundle branch type morphology with a late transition, and a right inferior axis. (B) A 98% pace-map match from posteroseptal right ventricular outflow tract. (C) A right anterior oblique of the left ventricle with red dots representing ablation lesions. (D) A postero-anterior projection of the right ventricle with red dots representing ablation lesions. This patient did not have any recurrent ventricular tachycardia but succumbed to respiratory failure.
Long-term management
After the initial VES episode is controlled, prompt consideration must be given to the requirement of ICD implantation if the patient is without one. If no reversible causes are identified, then an ICD implantation for secondary prevention is encouraged by the current guidelines.5In-hospital and post-discharge cardiac rehabilitation is recommended and has been shown to not increase the risk of recurrent VES.120
Conclusion
Ventricular electrical storm is a cardiac emergency that requires swift intervention. It is associated with poor short and long-term outcomes. An astute clinician must be aware of rapid troubleshooting on initial assessment, be familiar with the multitude pharmacotherapeutic options, and refer for CA when warranted. A multipronged approach is frequently needed for device interrogation, advanced cardiac life support, cardiac intensive care for monitoring and drug administration, electrophysiological assistance for CA, and surgical backup for CSD if indicated. While we have come a long way over the last few decades, further research would be paramount to improve the outcomes of patients with VES.
Supplementary material
Supplementary material is available at Europace online.
Conflict of interest: none declared.
References
Second Chinese Cardiac Study (CCS-2) Collaborative Group.
