Management of Ventricular Electrical Storm: A Contemporary Appraisal

Gurukripa N. Kowlgi; Yong-Mei Cha

Europace. 2020;22(12):1768-1780.

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):

(Enlarge Image)

Figure 1.

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.

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.

1 2 3 4 5 6 7

Next Section

Europace. 2020;22(12):1768-1780. © 2020 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.

Table 1. 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	I _Na, I _Kr, I _to, 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	I _Na, I _Kr	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	I _Na	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	I _Na	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	I _Kr; β_1,2	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	I _Na, I _Ca, I _Kr, I _K1, I _Ks, I _to, 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	I _Ca	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; I _ca, L-type calcium channel current; I _K1, inward rectifier potassium channel; I _Kr, rapid delayed rectifier potassium current; I _Ks, slow delayed rectifier potassium current; I _Na, fast inward sodium current; I _to, 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.

Supplementary Table S1. Summary of clinical trials of ventricular arrhythmias. The criteria, epidemiology, frequency, and details of ventricular electrical storm are described. The mortality outcomes and the details of device therapies are enlisted as well.
Year	Authors	Mean age (years)	Criteria	Frequency	Predominant VA	Number of VA episodes per event	Follow-up (months unless specified)	Mortality outcome (VES vs. no VES)	ICD therapies
1997	Fries et al.¹	61±9 (range 31 -73)	≥2 VT separated by 1h of SR	34/57 (59.6%)	82% VT; 18% primary VF	Not reported	36±18 (range 2–67)	Increase (29% in VES vs. 4% without VES, p <0.05)	43% ATP alone; 23% shock alone; 25% both
1998	Credner et al.²	61±14 (range 23–79)	≥3 VT/24h	14/136 (10.3%)	57% VT; 21% VF; 21% both	Mean = 17 ± 17 (Range 3 – 50)	403±242 days	No significant difference	Not reported
2000	Greene et al.³	60.2±13.9	≥3 VT/24h	40/227 (17.6%)	65% VT, 25% VF	Mean = 55.1 ± 90.6	2.9±2.6 years	No significant difference	23% ATP alone, 77% shock ± ATP
2000	Bansch et al.⁴	56±12	≥3 VT/24h	30/106 (28.3%)	70% mVT, 20 % VF/pVT	Median=19 (range 4 – 440)	33±23	Increase; RR=2.3 (1.11–4.77), p<0.04	Not reported
2001	Exner et al.⁵	67±11	≥3 VT/24h	90/457 (19.7%)	86% VT; 14% pVT/VF	Median = 4 (range 3 – 14)	31±13	Increase; RR=2.4 (1.3–4.2), p =0.003	28% ATP alone; 46% shocks alone; 26% both
2004	Verma et al.⁶	66±12	≥2 VT/24h	208/2028 (10.2%)	52% VT; 48% VF	Not reported	588±380 days	Increase (p=0.001)	Mean 5 ± 5 shocks/patient/24 hours (Range 2 – 43)
2005	Stuber et al.⁷	56±14	≥3 VT/2 wk	51/214 (23.8%)	93% VT, 7% pVT/VF	Median = 8 (range 3 – 1200)	3.3±2.2 years	Increase (87% in VES, vs. 67% without, p=0.026)	50% ATP alone, 31% shock alone, 19% both
2005	Gatzoulis et al.⁸	64±9	≥3 VT/24h	32/169 (18.9%)	78% VT, 22% pVT/VF	Not reported	33±26	Increase (RR 2.13,p=0.03)	ATP: 21 ± 33/episode Shock: 8 ± 4/episode
2006	Hohnloser et al.⁹	62±11	≥3 VT/24h	148/633 (23.4%)	91% VT; 1% VF; 8% both	Median = 5 (range 3 – 11)	Median : 7 (IQR 2 – 12.3)	No change	70% ATP alone; 7% shocks alone; 23% both
2006	Arya et al.¹⁰	53±19	≥3 VT/24h	22/162 (13.6%)	Not reported	Not reported	14.3±10	Not reported	Not reported
2006	Brigadeau et al.¹¹	60±14	≥2 VT/24h	123/307 (41.4%)	90% VT; 2% pVT; 8% VF	Range = 2 to ≥15	Median: 826 days (IQR 1141 days)	No change	26% ATP alone; 18% shocks alone; 56% both
2007	Sesselberg et al.	65±11	≥3 VT/24h	27/719 (3.8%)	74% VT; 26% VF	Not reported	20.6±12.8	Increase (RR 7.4, p <0.01)	4% ATP alone, 85% shocks
2018	Kwaśniewski et al.¹²	60.7±9.1	≥3 VT/24h	50/416 (12%)	54% VT; 6% VF; 40% both	Median 6 (Range 3 -140)	66	Increase (50% vs. 30%, p = 0.036)	15% ATP alone; 85% shock±ATP
2020	Elsokkari et al.¹³	66.5±8.7	≥2 VT/3 months	465/1764 (26.4%)	Not reported	Range = 3 to ≥10	Median 40.1 (IQR 24.6–55.9)	Increase (HR 2.68, p<0.0001)	For clusters within 24 hours ATP alone 34.9%; Shocks±ATP 50.8%

Abbreviations: VES: Ventricular electrical storm; VT: Ventricular tachycardia; VF: Ventricular fibrillation; SR: Sinus rhythm; h: hour; wk: week; ATP: Antitachycardia pacing; VA: Ventricular arrhythmia; ICD: Implantable cardioverter-defibrillator; RR: Relative risk

Supplementary Table S2. Summary of clinical trials of catheter ablation for ventricular electrical storm. The sample size, and description are provided. The outcomes in terms of ventricular arrhythmia recurrence, and survival are listed.
Year	Authors	Sample size	Sample description	Control	Follow-up (months unless specified)	Recurrence free (%)	Survival (%)
2007	Reddy et al.¹⁴	128	ICM	Med	22.5±5.5	CA:88; Med:67 p=0.007	CA:91; Med:83, p=NS
2010	Kuck et al.¹⁵	107	ICM	Med	23±9.7	CA:47; Med:29 p=0.04	CA:93; Med:91, p=NS
2012	Di Biase et al.¹⁶	92	ICM (Endocardial-epicardial substrate modification)	Partial substrate modification	25±10	Endo: Epi 81 Partial: 53 p=0.006	98% vs 98% p=NS
2012	Izquierdo et al.¹⁷	23	ICM CA: 83; Med:66	Med:23	28	CA:68; MT:71 P=NS	CA:70; Med:48, p=NS
2013	Nayyar et al.¹⁸	471	Meta-analysis of 39 studies consisting of 68% ICM patients	N/A	Median 58 weeks (Range 4 – 156)	60	83
2016	Özcan et al.	44	ICM, refractory VES	N/A	28	55	82
2016	Sapp et al.¹⁹	259	ICM, refractory VT	Med:127	Mean 27.9±17.1	CA:62, Med:54, p=NS (Composite outcomes better in CA vs. Med)	CA:72.7; Med:72.4, p=NS
2016	Santangeli et al.²⁰	427	Pooled analysis of 14 trials on ICD patients	Med: 2268	15 ± 6	CA: 61; Med:46, p=0.001	CA: 93; Med: 90%, p=NS
2017	Muser et al.²¹	267	ICM and NICM; 22% endo-epi ablation	N/A	45	67	71
2017	Kumar et al.²²	287	64% ICM	36% NICM	12	ICM: 51; NICM: 36 p=0.007	ICM:75; NICM:72 p=NS
2017	Jin et al.²³	54	ICM, RMN guided ablation	N/A	17	50	80
2017	Morawski et al.	28	81% ICM	Med: 42	28	CA: 43; Med: 26, p=NS	CA: 86; Med: 62, p=0.03
2017	Kuck et al.²⁴	107	ICM	Med	2.3 ± 1.1	CA:54; Med:54, p=NS	CA:83; Med:81, p=NS
2019	Komatsu et al.²⁵	110	Retrospective. Post-MI VF storm	None	Median 3.7 years (IQR 1.4–6.5 years)	82%	Not reported
2020	Chung et al.²⁶	81	Retrospective. VES requiring MCS (32%), vs. no MCS (68%)	No MCS	12	VA recurrence 15.4% in MCS and 30.9% without MCS (p=NS)	Mortality 42.3% in MCS and 9.1% without MCS (p=0.001)

Abbreviations: ICM: Ischemic cardiomyopathy, NICM: Non-ischemic cardiomyopathy, VES: Ventricular electrical storm; VT: Ventricular tachycardia; VF: Ventricular fibrillation; RMN: Remote magnetic navigation; MI: Myocardial infarction; MCS: Mechanical circulatory support; CA: Catheter ablation; Med: Medical therapy