Electrophysiology and Arrhythmia: Review Article

Cardiology
Cardiology 2023;148:119–130 Received: October 25, 2022
Accepted: February 8, 2023
DOI: 10.1159/000529670 Published online: March 6, 2023

Pharmacotherapy in Ventricular
Arrhythmias
Nachiket Apte Dinesh K. Kalra
Division of Cardiology, University of Louisville School of Medicine, Louisville, KY, USA

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

Keywords ventricular arrhythmia suppression and prevention of sud-
Ventricular arrhythmias · Anti-arrhythmic drugs · Sudden den cardiac death, antiarrhythmics are now used to reduce
cardiac death · Ventricular tachycardia implantable defibrillator shocks and symptoms. They still have
a role in premature ventricular complex suppression in patients
with failed catheter ablation or those who are not candidates
Abstract for invasive therapy. Newer concepts in cardiac imaging and
Background: Ventricular ectopy is observed in most of the the use of artificial intelligence may help further delineate
population ranging from isolated premature ventricular con- sudden cardiac risk and identify patients that may benefit from
tractions to rapid hemodynamically unstable ventricular pharmacological management. Key Message: Anti-arrhythmic
tachyarrhythmias like ventricular tachycardia and ventricular agents continue to perform an important role in the sup-
fibrillation. Multiple mechanisms exist for ventricular arrhyth- pression of ventricular arrhythmias especially channelopathies,
mias such as triggered activity, reentry, and automaticity. Scar- polymorphic VT, and idiopathic ventricular fibrillation. Judi-
based reentry forms the basis of most malignant VA that can cious use of these agents while recognizing side effects can
lead to sudden cardiac death. Many antiarrhythmic drugs have help reduce the long-term effects of ventricular arrhythmias on
been utilized for the suppression of ventricular arrhythmia. cardiac function. © 2023 S. Karger AG, Basel
They are commonly classified using the Vaughan Williams
Singh classification which distinguishes them based on the
predominant action on different phases of the cardiac action
potential. Class Ic agents are widely used in premature ven- Introduction
tricular contraction suppression but are contraindicated in
patients with prior myocardial infarction or ischemic scar and Ventricular ectopy encompasses a spectrum of ven-
heart failure. β-Blockers continue to be a mainstay in the tricular arrhythmia (VA) ranging from isolated
treatment of most symptomatic VA and are well tolerated, asymptomatic premature ventricular contractions
relatively safe, and have additional benefits in symptomatic (PVCs) to rapid ventricular tachycardia (VT) and
coronary heart disease and left ventricular systolic dysfunction. ventricular fibrillation (VF) which may lead to sudden
Amiodarone continues to be used for the management of cardiac death (SCD). The incidence of PVCs in the
most cases of serious VA especially in the acute setting when population is highly dependent on patient characteris-
accompanied by hemodynamic perturbations but has the tics including comorbidities as well as the duration of
disadvantage of having a poor toxicity profile for long- monitoring. In a healthy military population, PVCs were
term use. Summary: Historically used for long-term found in only 0.6% of people <20 years of age on a

[email protected] © 2023 S. Karger AG, Basel Correspondence to:

www.karger.com/crd Dinesh Kalra, dinesh.kalra @ louisville.edu
routine screening electrocardiogram (EKG). However, increased risk with NSVTs, especially in the acute
the prevalence increased to >2.7% in those 50 years of myocardial infarction (AMI) population [8].
age or older [1]. Traditionally, the incidence of PVCs has Sustained VT and VF are associated with a high risk of
been determined based on the EKG and/or limited SCD. VAs in the acute MI setting may frequently be
Holter monitoring. However, increasingly with long- polymorphic or present as VF while monomorphic VT in
term monitoring that includes implantable monitors, the CHD population is suggestive of scar-based reentry. VT
portable devices, and wearables, the incidence of PVCs or VF in the non-ACS population is suggestive of scar-
is likely to be far greater. For example, in the Ath- based reentry, metabolic disorders as well as inherited
erosclerosis Risk in Communities (ARIC) study which cardiomyopathies either secondary to myocardial degen-
used 2 min of EKG monitoring or the Framingham eration or channelopathies. Lastly, triggered activity in the
study which used 1 h, the incidence of PVCs was 5.5% form of early after depolarizations (EADs) as well as
and 12%, respectively, and was more than twice as delayed after depolarizations (DADs) has been implicated
likely in the population with coronary heart disease in initiation of VAs. EADs occur in phases 2 and 3 of the
(CHD) [2, 3]. When healthy adults were monitored on action potential and may give rise to VAs in conditions like
24-h Holter monitoring, the incidence of PVCs was prolonged QT and heart failure while DADs arise during

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

found to be as high as 69% with the median number of phase 4 of the action potential resulting in high intracellular
PVCs being two. More recently, in the Multiethnic Ca+2 release and are usually seen in conditions like digitalis
Study of Atherosclerosis (MESA) study, the incidence toxicity, high catecholamine release like Catecholaminergic
was as high as 99.5% in 1,122 individuals who wore a Polymorphic Ventricular Tachycardia (CPVT) as well as
Zio Patch XT® (iRhythm Technologies, Inc, San dyselectrolytemia.
Francisco, CA) for 14 days [4]. It is likely that with Management of VAs is a multipronged approach that
increasing implantable and/or wearable technologies, includes general care, pharmacological therapy as well as
every individual would likely have some ventricular procedures like catheter ablation. Moderation of alcohol and
ectopic activity at a point in time with long enough caffeine and management of stress may help in decreasing
monitoring. Thus, such kind of data is needed to inform PVCs. In this review article, we will take a look at commonly
guidelines as to what constitutes normal or benign used pharmacological agents to treat or prevent VAs.
findings and what burden of VA in patients with
structural heart disease confers a higher risk of SCD.
Typically, PVCs – especially if they are multifocal and Classification of Anti-Arrhythmic Agents
frequent, defined as more than 1,000 in 24 h – have
been considered a risk factor for major adverse car- Pharmacological agents for the prevention or treatment
diovascular outcomes including heart failure, stroke, of VAs can be broadly classified using the Vaughan Wil-
and SCD. A recent study by Refaat et al. [5] showed that liams Singh classification which divides medications into
in asymptomatic individuals, PVCs during recovery classes depending on the predominant mechanism of
that were frequent (>10 per minute), multifocal, or channel or receptor-blocking action as shown in Figure 1
complex (R-on-T type, or ≥2 PVCs in a row) were [9]. Though the most widely used, it has several limitations
associated with increased long-term cardiovascular and may not accommodate all anti-arrhythmias. Most
mortality while exercise-induced PVCs did not have the prominently, drugs like amiodarone may have actions
same risk profile. across classes. Classification systems like the Sicilian Gambit
On the other hand, VA such as VT and VF have a classification and a modernized Oxford classification by Lei
distinct risk profile when compared to isolated PVCs. and colleagues have been proposed [10, 11]. As shown in
Nonsustained VT (NSVT), defined as VT lasting less than Table 1, these systems can be overlapped to describe the
30 s, is challenging in terms of prognosis and predict- anti-arrhythmic effects of each drug and to accommodate
ability for SCD. It remains to be seen if it is a precursor for drugs that have actions across multiple channels.
sustained VT and SCD or simply a marker for the un-
derlying myocardial disease [6]. In the MERLIN-TIMI 36
trial, there was no increased risk with NSVT lasting 3 Class I
beats; however, in the subgroups with 4–7 beats and more
than 8 beats, the risk of SCD was statistically higher [7]. Medications in this class have been used for a long time
Interestingly, it was observed in populations with and for the prevention of sudden death. They primarily act by
without high risk. Other studies have not found any reducing peak INa and increasing the excitation threshold.

120 Cardiology 2023;148:119–130 Apte/Kalra

DOI: 10.1159/000529670
 Color version available online
Fig. 1. Ventricular myocardial action po-
tential and primary actions of common
anti-arrhythmic drugs.

received one of three drugs – encainide, flecainide, or

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

Given their arrhythmic effects as well as increased mor-
tality in patients with myocardial infarction and structural moricizine or placebo. At a median follow-up of 10
heart disease, their use is limited. They are divided into months, the trial was stopped early after it was noted that
three classes as given in Table 1; however, newer classi- patients in the drug arm had higher deaths from ar-
fications have additional subclasses depending on other rhythmias as well as higher all-cause mortality than in the
actions. We will discuss the more commonly used anti- placebo arm. This trial’s findings changed concepts and
arrhythmic drugs as given. guidelines regarding the use of this class of antiar-
rhythmic drugs for the suppression of VA. Notably,
Flecainide deaths were observed even in patients with EF >40% [18].
Flecainide was originally developed as a new fluori- Multiple factors may explain these findings. Flecainide
nated anesthetic but was found to have anti-arrhythmic exerts a negative inotropic effect by decreasing stroke
properties. It was approved in 1984 for suppression of volume and increasing pulmonary capillary wedge pres-
sustained VT [12]. It is a potent and selective blocker of sures, even when administered to patients with normal
the cardiac fast inward sodium (Na+) current with high ejection fraction. Even in patients with CPVT, flecainide
affinity in the open state. It has also been shown to inhibit can bind to separate activation and inhibition sites on
the delayed rectifier IKr current. Due to this action, it RyR2, with activation dominating in lower activity chan-
shortens Na-regulated action potential duration (APD) in nels and inhibition dominating in more active channels,
Purkinje fibers but prolongs it in the atrial and ventricular thus having a potential pro-arrhythmic effect [19].
muscle fibers which are regulated by the fast K channel IKr Flecainide is currently administered for suppression of
[13]. It blocks the opening of the ryanodine receptor, thus PVCs in structurally normal hearts without a history of
inhibiting the release of Ca++ from the sarcoplasmic myocardial infarction or heart failure where it has a class
reticulum thereby decreasing triggered activity. This IIa indication [14]. It has been shown to significantly
makes it a potent inhibitor of CPVT, associated with suppress RV outflow tract PVCs. It has been shown to
ryanodine and calsequestrin mutations [14]. suppress exercise-induced VAs in both genotype-positive
Flecainide increases the sinus node recovery time and patients [20], as well as genotype-negative patients [21] as
delays intra-atrial and atrioventricular conduction, thus well as prevent ICD shocks in CPVT patients in com-
increasing the PR, QRS, and QT intervals without an bination with β-blockers [14].
increase in QTc duration [15]. It may cause an increase in It is usually administrated twice daily and is absorbed
the pacing threshold; however, no adverse impact has with a bioavailability of 90%. PR and QRS duration may
been noted in patients with pacemakers including those be prolonged in a dose-dependent manner with toxic
utilizing conduction system pacing [16, 17]. doses causing bradycardia and conduction abnormalities.
The pro-arrhythmic effects of flecainide were well
highlighted after the findings of the CAST trial which Propafenone
tested the effect of class Ic anti-arrhythmic agents in Propafenone also blocks the fast inward sodium
patients with asymptomatic or mildly symptomatic VA in channel like flecainide; however, it has additional β
patients with myocardial infarction [18]. Patients blocking and calcium-blocking activity. Like Flecainide it

Pharmacotherapy in Ventricular Cardiology 2023;148:119–130 121

Arrhythmias DOI: 10.1159/000529670
 Table 1. Classification of anti-arrhythmic drugs using current and proposed classification systems

122
Drug Vaughan Characteristics Metabolism Dosing Current use in VA Caution
Williams Singh
class
(modernized
class)

Ivabradine (0) If blocker Hepatic CYP3A4 2.5 mg–7.5 mg twice Has been used for Bradycardia, QT
daily suppression of VT prolongation with
in CPVT other AADs
Predominantly Sodium Channel Blockers
Quinidine Ia Medium Na blocker with CYP2D6 Sulfate – 200–300 mg sQTS1, Brugada, Cinchonism, poor
K+channel blocking three to four times ERS, ES availability, QT
action daily prolongation
Hydroquinidine-

DOI: 10.1159/000529670
600–900 mg daily

Cardiology 2023;148:119–130
Procainamide Ia Medium Na+ blocker Acetylation 450–900 mg daily in MMVT Unmask BrS QT prolongation, Lupus
with K+ channel blocking 2–3 divided doses Decrease ICD like symptoms,
action shocks Agranulocytosis
Disopyramide Ia Medium Na+ blocker CYP3A4 250–750 mg daily None for VA Negatively inotropic,
with K + channel – hepatic prevention or QT prolongation
Renal excretion treatment
Lidocaine Mexiletine Ib Fast Na+ channel blocker 95% hepatic Lidocaine – no oral TdP, MMVT and Tremors
CYP3A4 dose PMVT, VF
I.V. – 50–200 mg bolus Mexiletine – LQTS3
Maintenance 1–4 mg/
min
Mexiletine – Oral
400 mg followed by
200–400 mg three
times daily
Flecainide Ic Slow Na+ channel CYP2D6 50–150 mg twice daily PVC suppression Prolong PR, QRS
blocker (class IVb RyR2 Renal LQT3 Proarrhythmic,
Ca2+ receptor blocker) drowsiness, headache
Propafenone Ic Slow Na+ channel CYP2D6 200–300 mg three PVC suppression Bronchospasm,
blocker (class IVb RyR2 CYP3A4 times daily prolonged PR QRS,

Apte/Kalra
Ca2+ receptor blocker) proarrhythmic
Ranolazine (Id) Late Na+ channel blocker CYP3A4, CYP2D6 500–1,000 mg twice Rarely used as 2nd Dizziness, constipation
Renal excretion daily line for PVCs
Combination
therapy for VT
Drugs affecting receptors of the autonomic system
Beta-blockers – nadolol, II(a) Nonselective (nadolol, Nadolol – renal Nadolol -40 -120 mg LQTS1, LQT2, CPVT Bradycardia may
propranolol, propranolol) and excretion daily (nadolol, worsen cardiogenic
metoprolol, carvedilol selective(metoprolol) without Propranolol propranolol), PVC, shock
beta blockers unchanged 80–320 mg daily and VT
Propranolol Metoprolol suppression with
– hepatic other AADs
– CYP2D6
Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025
 Table 1 (continued)

Drug Vaughan Characteristics Metabolism Dosing Current use in VA Caution

Williams Singh

Arrhythmias
class
(modernized
class)

Isoproterenol (IIb) Nonselective Beta Hepatic and lung 0.5–10 µg/min ES, TdP Tachycardia, sudden
activator MAOI and COMT hypotension
Atropine, hyoscyamine (IIc) M2 muscarinic blockers Hepatic I.V. 0.5–1.0 mg single Not routinely given Dry mouth,

Pharmacotherapy in Ventricular
– hydrolysis dose but reportedly constipation, confusion
reduced VA in
AMI (70)
Digoxin (IId) M2 muscarinic activators p-glycoprotein No data for Digoxin toxicity,
Na/K ATPase antagonist Renal excretion routine use bidirectional VT
Adenosine (IIe) Adenosine A1 blocker In blood Used to Dyspnea, facial flushing
differentiate WCTs. (transient)
Not given for
treatment
Predominantly Potassium channel blockers
Amiodarone III(a) Nonselective K+ blocker Hepatic – Loading dose – oral PVCs Liver, thyroid, skin,
Blocks β receptors CYP3A4 – 600–1,200 mg/24 h VT corneal toxicity, lung
No dose change for 8–10 days VF fibrosis with long-term
in renal I.V. – 150 mg IV bolus use. Requires routine
dysfunction followed by 1 mg/min surveillance with
infusion for 6 h prolonged use
followed by 0.5 mg/
min over 18 h
Maintenance
Oral – 200–400 mg/day
I.V. −0.5 mg/min

DOI: 10.1159/000529670
Dronedarone III(a) Nonselective K+ blocker Hepatic CYP3A4 400 mg BID Limited data
for use

Cardiology 2023;148:119–130
Dofetilide III(b) IKr blocker Renal excretion 125–500 mg BID Limited data for QTc prolongation
Renally dosed use in VA
Sotalol III(b) IKr blocker Not metabolized Oral – 80–160 mg BID PVC and VT QTc prolongation,
Renal excretion Renally dosed suppression bradycardia
I.V. form
Calcium channel blockers
Verapamil Diltiazem IV(a) Calcium channel blocker Hepatic – PVC suppression, Bradycardia, caution in
CYP3A4 CPVT heart failure

AAD, anti-arrhythmic drug; AMI, acute myocardial infarction; BrS, Brugada syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; CYP,
Cytochrome P; COMT, Catechol-O-methyl transferase inhibitors; ERS, early repolarization syndrome; ES, electrical storm; LQTS, long QT syndrome; MAO,
monoamine oxidase inhibitors; MMVT, monomorphic ventricular tachycardia; PVC, premature ventricular contraction; RyR2, ryanodine receptor 2; sQTS, short QT
syndrome; WCT, wide complex tachycardia; VT, ventricular tachycardia; VF, ventricular fibrillation.

123
Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025
reduces the prolongation of conduction and refractori- Procainamide
ness in all areas of the myocardium, particularly in the Procainamide is a benzamide, similar to procaine but
intraventricular conduction. Its bioavailability is dose- with an amide moiety which gives it a longer half-life. It
dependent and it also shows use dependence. It is ef- and its active metabolite N-acetyl – procainamide block
fective in suppressing PVCs as well as NSVT. Though sodium channels delaying phase 0 of the cardiac cycle.
contraindicated in patients with low ejection fraction, it They also block the rectifier K+ channel, IKr. Procaina-
has been given in small studies with improvement in mide is used to rapidly terminate monomorphic VT. In
ejection fraction [22]. It has also been described for CPVT the PROCAMIO study, it was shown to have lesser
with its benefit likely from its β blocking action [14]. cardiac adverse effects than amiodarone (9% vs. 41%, p,
It is metabolized in the liver via the cytochrome P450 0.006%) with an almost double the incidence of VT
2D6 (CYP2D6) pathway. Alcohol may increase prop- termination (67% vs. 38%, p, 0.026) [27]. It was also
afenone levels even at regular doses [23]. Propafenone is shown to be superior to lidocaine in terminating acute VT
also pro-arrhythmic though the action is more likely due episodes in a small randomized trial of 29 patients [28].
to its actions on delaying His-Purkinje conduction which However, in another study, procainamide recipients who
may allow for ventricular reentry. received more shocks and pharmacologic interventions

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

and had lengthier resuscitations were less likely to survive
Lidocaine and Mexiletine hospital discharge, though these results were probably
Lidocaine and its oral form mexiletine bind to Na confounded by the administration of other cardiac
channels in the inactivated state and rapidly unbind medications [29]. Oral procainamide was also shown to
during the resting state. They demonstrate use-dependent reduce sustained VT and VF as well as ICD therapies in a
inhibition of fast Na+ current at higher heart rates while at small study of 34 patients [25]. Though 55% of these had
low heart rates, they mostly block late Na+ current [24]. a previous catheter ablation for VT, it was initiated after
In animal studies, mexiletine dose-dependently short- VT was inducible in these patients [25]. Though this
ened APD in mid-myocardial cells and decreased could be a confounding factor, it is not necessarily a
transmural dispersion of repolarization. It also prevents negative study as a combination of anti-arrhythmias and
torsades de pointes (TdP) by inhibiting late sodium catheter ablation are routinely used to decrease the
channels (INa-L), a property that makes it a useful agent burden of VT and ICD therapies in everyday practice.
and a class I agent in the 2022 ESC guidelines for pre- Currently, procainamide is mainly used in the acute
venting TdP in LQT3 a disorder involving the sodium setting to terminate monomorphic VT not amenable to
channel [14]. It increases QRS duration at higher heart IV amiodarone or lidocaine [27, 28]. In the 2022 ESC
rates but does not prolong QTc. In the VANISH trial, Guidelines for the management of VAs, it has a class IIa
mexiletine and amiodarone were found to be inferior recommendation for acute management of idiopathic VT
when compared to catheter ablation when compared for over other AADs like amiodarone and sotalol which are
the composite outcome of death, electrical storm, or class IIb [14]. Being a sodium channel blocker like fle-
appropriate ICD shock [25]. cainide, it can unmask Brugada syndrome (BrS) and is
Lidocaine is used in the IV form for the suppression of used for provocative testing in patients with BrS [25].
sustained VT and VF including electrical storm and is
now used as an adjunct or alternative to amiodarone [14]. Quinidine
In early trials, out-of-hospital cardiac patients random- Quinidine is a stereoisomer of the antimalarial drug
ized to amiodarone or lidocaine had lesser episodes of quinine. Given a class Ia agent, its effect on conduction
subsequent shocks or required CPR and were more likely velocity is lesser than lidocaine but greater than class Ic
to survive hospitalization than those receiving a placebo, agents. Like procainamide, it also acts on IKr and IKs with
however, rate of survival or favorable neurologic outcome an additional blocking action on the L-type ICa and the
was not significantly higher in the anti-arrhythmic group. late INa inward currents Ito with prolongation of the APD.
Initially used for the treatment of VAs in ischemic VT, it It is primarily used as a second line or an adjunctive drug
has now been superseded by amiodarone in the acute for drug-resistant VT. It has been shown to reduce drug
setting due to lack of any substantial benefit [14]. A large refractory idiopathic and post-infarct polymorphic VT in
meta-analysis showed equivocal results for both amio- patients with ischemic heart disease [14]. Recently in a
darone and lidocaine with regard to survival at hospital small retrospective analysis, quinidine initiation reduced
admission though there was no difference in the long- recurrent VA in patients hospitalized with electrical
term outcome [26]. storm though about 54% of patients had recurrent VA

124 Cardiology 2023;148:119–130 Apte/Kalra

DOI: 10.1159/000529670
post-discharge [30]. More, as a strong Ito blocker, it has blockers, especially nonselective β blockers like nadolol
been studied in J wave syndromes, namely, BrS and early were found to be associated with lesser SCA, ICD shocks,
repolarization syndrome (ERS). It has been shown in or syncope [14].
multiple small studies to reduce ectopy-induced recurrent
VAs in BrS both at initiation and follow-up [31] as well as
reduce ICD shocks in observational cohorts [32]. In ERS, Class III
quinidine may reduce the early repolarization pattern or
even restore a normal ECG in patients [33]. Even in Sotalol
acquired ERS secondary to hypothermia, quinidine has Sotalol, a racemic mixture of d- and l-isoforms, is a
been administered to reduce VF due to its ability to nonselective β-blocker but differs from other drugs in its
reverse hypothermia-induced repolarization abnormali- class by also having class III inhibition of delayed po-
ties [34]. Quinidine, because of its potassium-blocking tassium rectifier channel. It is thus able to increase APD
action has been shown, particularly in patients with a and ERP. Sotalol has been shown to reduce VAs and
KCNH2 mutation (sQTS type I), to increase QTc du- suppress PVCs. It exhibits reverse use dependence,
ration, prolong ventricular refractory period and prevent binding more avidly in slower heart rates. It has been

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

induction of VF during EPS though its action on other shown to reduce ICD shocks with no difference in
mutations for SQT is not completely understood [35]. It mortality. The use of pure d-sotalol, with predominantly
currently has a class IIa indication for management of potassium-blocking action with no clinically significant
polymorphic VA secondary to BrS, ERS as well as idi- β-blocker activity, was shown to have higher mortality in
opathic VF and a class IIb indication for PVC-induced the SWORD trial which was subsequently stopped [25].
polymorphic VAs [14]. In a large meta-analysis of 22 randomized trials, when
compared to amiodarone, sotalol significantly increased
VT recurrences and ICD shocks [38]. It remains a
Class II second-line drug for managing PVCs and VT in those
patients who are intolerant or refractory to amiodarone.
β-Blockers Sotalol requires dosing depending on QTc and renal
β-Blockers manifest their anti-arrhythmic activity in clearance. More recently, IV sotalol has been used for
multiple ways. In the ischemic population, β-blockers rapid loading in 1 day versus the conventional 3-day
predominantly have an anti-ischemic action and serve to dosing. It has been shown to rapidly increase the ven-
decrease myocardial oxygen demand, slow heart rate to tricular refractory period and terminate sustained
allow ventricular filling, as well as possibly prevent plaque VT [39].
rupture. Sympathetic activity increases post-AMI and
that can predispose to VA by lowering the VF threshold Dofetilide
[36]. β-Blockers inhibit catecholamine-initiated cAMP Dofetilide is a selective delayed IKr blocker that is
activation and may exert their anti-arrhythmic effect by approved for use in atrial tachyarrhythmias. However, its
sympathetic blockade and membrane stabilizing activity use in VAs is less established with mixed results in trials.
[25]. Due to their safety profile, availability as well ad- It has been used in select settings for reducing ICD
renergic blockade, β-blockers are among the first-line therapies as well as the recurrence of VT where other
agents for the prevention of VA in the CHD pop- AADs have not been successful [25].
ulation. In the nonischemic population, possible mech-
anisms include slowing of the sinus rate as well as Amiodarone
inhibition of the ryanodine receptor, the mutation of Amiodarone functions as an inhibitor of the IKr
which is an important mechanism in CPVT. channel but also has actions on the sodium channel as
β-Blockers like nadolol and propranolol have been well as an anti-adrenergic action. It remains the most
used in LQTS and CPVT. Nadolol has long been used in commonly prescribed drug for supraventricular and VAs.
LQTS1 and LQTS2. They are thought to have a heart It increases refractoriness in all tissues as well as the SA
rate-dependent decrease in the QT interval and are the and AV nodes. It uniformly delays ventricular depolar-
first line in decreasing syncope and mortality in the ization in all myocardial layers leading to QT prolon-
LQTS1 and LQTS2 populations [37]. Though all β- gation without any increased transmural heterogeneity of
blockers are effective, nadolol has shown significant repolarization. Thus, TdP is, however, rare and in general,
risk reduction in LQTS2 patients. Similarly, in CPVT, β- amiodarone has a better safety profile in terms of

Pharmacotherapy in Ventricular Cardiology 2023;148:119–130 125

Arrhythmias DOI: 10.1159/000529670
inducing arrhythmias [40]. However, a 2017 study by Dronedarone
Shenthar et al. [41] has shown that IV amiodarone has a Dronedarone is structurally related to amiodarone
higher risk of inducing TdP than oral amiodarone, a without the iodine moiety. It has mainly been studied
finding shared by other studies with female sex, con- retrospectively when used for AF patients where patients
comitant drug therapy, left ventricular dysfunction, and on dronedarone have lower rates of sustained VA. No-
electrolyte abnormalities being at higher risk. It has been tably, its use is limited due to the lack of randomized
given for a long term for the suppression of VT and VF controlled trials as well as its contraindication in heart
before the popularization of ICDs. Multiple large trials failure [25].
have shown the benefit of amiodarone for the secondary
prevention of VT and VF. The EMIAT and CAMIAT
trials showed that amiodarone reduced the incidence of Class IV
VF or arrhythmic death among MI patients [25]. The
CASCADE study was a randomized trial that showed Calcium Channel Blockers
that cardiac arrest survivors with ICDs on amiodarone Nondihydropyridine calcium channel blockers like
had a lesser incidence of the composite of cardiac death verapamil and diltiazem are generally contraindicated in

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

and sustained VA. Amiodarone reduces the incidence of most ventricular tachyarrythmias due to their propensity
VF or arrhythmic death among survivors of AMI, to cause severe hemodynamic collapse secondary to
sustained VT/VF, or syncope and ICD shocks when hypotension and death [43]. In patients with structurally
compared to class Ic antiarrhythmics. Other trials have normal hearts, calcium channel blockers have been
shown similar results with other antiarrhythmias [26]. shown to reduce outflow tract PVCs. Verapamil can
When compared to ICDs, however, ICDs showed a suppress calcium-dependent slow conduction. Fascicular
greater mortality reduction in multiple trials which VT is a unique subtype of VT. It is thought to be a re-
compared ICDs to medical therapy, namely, amiodar- entrant tachycardia where one of the fascicles is the
one. In the CIDs study, the risk reduction was non- anterior limb, thus making it a relatively narrow complex
significant, however, long-term follow-up showed tachycardia. Verapamil is most effective in terminating
significance toward the ICD group, namely, from side fascicular VT as this VT is initiated in a verapamil
effects and discontinuation of long-term amiodarone. sensitive slow conducting zone near the His bundle/left
The AVID study followed patients randomized to ICDs bundle region [44]. Partially depressing sodium channel
versus medical therapy, namely, amiodarone, over conduction seems to also play a part as lidocaine can slow
4 years and found ICDs to be superior. A meta-analysis down and terminate fascicular VT with variable success.
of all these trials showed significant risk reduction in In the 2022 ESC guidelines, it has a class I indication for
death from arrhythmia from ICDs with patients with an fascicular VT and a class IIa indication for idiopathic
EF of less than 35% deriving the most benefit [42]. Thus, VF [14].
amiodarone has fallen out of favor as a standalone drug
for secondary prevention, though it is often given Other Medications
concomitantly to reduce the incidence of VT in these Ranolazine
patients. A combination of β-blockers and amiodarone Ranolazine is a late Na+ channel blocker but also
in patients has been shown to reduce cardiac death and blocks the delayed rectifier current IKr. With its Na
arrhythmic death or resuscitated cardiac arrest. blocking action, it inhibits DADs and decreases trans-
Though there is plenty of clinical data for the short- mural dispersion of repolarization by decreasing APD in
term use of amiodarone for VT suppression, there is a the mid-myocardial cells, while increasing it in epi-
concern for short-term and long-term amiodarone use, cardial cells, thus decreasing EADs and reducing the risk
especially its toxic effects on the liver, thyroid, skin, eyes, of PMVT, especially in LQTS3. The multicenter RAID
and lungs. A meta-analysis of randomized trials com- trial compared ranolazine to placebo in ICD patients
paring amiodarone to placebo estimated the 1-year risk of with ischemic and nonischemic cardiomyopathy did not
these complications to be 0.6% for hepatic toxicity, 0.3% reduce the composite primary endpoint of ICD-treated
for peripheral neuropathy, 6% for hypothyroidism, and VT/VF or Death. However, it did reduce the number of
0.9% for hyperthyroidism while the risk of lung toxicity is VT or VF episodes significantly. The study was asso-
estimated to be 5–10% at doses of 400 mg/daily over ciated with almost 49% of patients discontinuing
5 years or above. Table 2 describes monitoring at initi- ranolazine during follow-up while 39% discontinued
ation and maintenance for AADs including amiodarone. placebo [25]. In the MERLIN-TIMI study, ranolazine

126 Cardiology 2023;148:119–130 Apte/Kalra

DOI: 10.1159/000529670
Table 2. Drug initiation and monitoring

Drug Initiation Monitoring

Flecainide Baseline EKG and ejection fraction EKG with dose escalation to monitor PR and QRS
Propafenone Baseline BMP duration. Consider plasma
levels to monitor toxicity
Stress testing to rule out underlying CAD
Mexiletine BMP, liver function test Liver function tests every 6 months. 0.8–2.0 μg/mL
Baseline EKG to monitor high-degree AV Block range for prevention of VA post-MI, however, side
effects are seen at lower doses. Drug monitoring in liver
disease, dose reduction for other side effects like
paresthesias and tremors
Sotalol BMP for creatinine clearance, baseline EKG for QTc Initiation – EKG 2–3 h after dose till 4–5 doses. BMP and
Dofetilide monitoring, cessation of QT-prolonging medications liver function tests at 6–12 months. EKG at follow-up
and monitoring for drug-drug interactions, hospital- Consider reinitiating if the drug is interrupted for more
based administration recommended for oral loading than 5 doses
Amiodarone Baseline EKG, liver function tests, thyroid function tests, BMP, liver function tests, and thyroid function tests

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

lung function testing, ophthalmological testing every 6 months
Ophthalmological evaluation every 12 months
Lung function testing for new dyspnea
HRCT for suspected lung toxicity
Beta-blockers Baseline EKG, BMP, liver function tests EKG at follow-up, routine laboratories every
6–12 months
Calcium channel Baseline EKG EKG at follow-up
blockers

Fig. 2. Cardiac MRI with both four-

chambered and short-axis views of a pa-
tient with high PVC burden and CAD with
a stent. No LGE was observed on delayed
contrast imaging. MRI, magnetic resonance
imaging; PVC, premature ventricular con-
tractions; CAD, coronary artery disease;
LGE, late gadolinium enhancement.

reduced VAs when compared to placebo on 7-day Magnesium and Calcium

Holter monitoring. Its antianginal effects may con- Magnesium and calcium play a significant role in
tribute to its anti-arrhythmic effects as seen in a small maintaining proper cardiac rhythm. Magnesium is
study where patients with angina had a better reduction required for the functioning of the Na+ /K+ ATPase
in VA when compared to patients for whom it was pump. It also interacts with calcium in maintaining
prescribed for its anti-arrhythmic use [45]. There is great low intracellular calcium levels. Hypomagnesemia
interest in its role in two conditions – namely, LQTS3 leads to higher irritability of cardiac tissue making it
and HOCM. In experimental models, ranolazine re- more susceptible to arrhythmias. The classic ar-
duced QTc interval at all heart rates in LQTS3 patients rhythmia is TdP and IV magnesium has been used
with the D1790G mutation [46]. successfully to treat TdP possibly by reducing early

Pharmacotherapy in Ventricular Cardiology 2023;148:119–130 127

Arrhythmias DOI: 10.1159/000529670
 Color version available online
depolarizations. Hypomagnesemia may increase the
toxicities of other drugs like digoxin and isoprotere-
nol. Similarly, calcium acts as a membrane stabilizer
and is given in the intravenous form for VT secondary
to hyperkalemia.

Isoproterenol
Isoproterenol or isoprenaline is a beta 1 and beta 2
agonist. It increases heart rate and thus shortens QT
interval. It is used to suppress polymorphic VT and VF in
patients with bradycardia and acquired long QT syn-
drome [14]. It is also used in electrical storm in patients
with BrS and SQTs as well as for suppression of poly-
morphic VT and VF in patients with acquired long QT
syndrome [14].

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

Challenging Existing Dogmas
Cardiac imaging including cardiac MRIs and PET Fig. 3. QTc interval measured by 6 lead EKG using the
scanning has helped better define myocardial scar. It KardiaMobile® portable monitor. Reproduced with permission
from AliveCor®.
remains to be seen if class Ic agents can be used to
suppress PVCs in patients who have no scar on cardiac
MRI despite having a history of coronary disease. As
shown in Figure 2, coronary artery disease may not developments, there has not been any drug or com-
always correlate with a scar. The CAST trial was pound that has been mainstream in the last 2 decades.
conducted before the advent of effective thrombolysis, Further work is needed in the development of drugs
primary PCI, and the remarkable efficiency of cath that can specifically target sites in the cardiac muscle
laboratory teams in managing patients with STEMI. cell thus avoiding systemic side effects. Recently,
There is increasing recognition that though ICDs have adeno-associated viruses were used to deliver the gene
a proven superiority over AADs when compared for the expressing cardiac calsequestrin (CASQ2) in a murine
prevention of SCD, they do not improve quality of life, model with CPVT2 secondary to CASQ2 gene
change ejection fraction or prevent VA. More studies knockout and mutation and were shown to increase
have pointed out a reduction in ICD shocks and VA CASQ2 expression resulting in lower VT events [49].
burden as a QoL measure versus SCD prevention alone. Arresting degradation of CASQ2 by administering
PVC burden ≥24% has been regarded as a risk factor for bortezomib, a proteasome inhibitor has been shown to
cardiomyopathy based on early studies. However, even lower PVCs in CPVT2 in a murine model [50].
PVCs with a lower burden can cause a decrease in
ejection fraction based on their location, coupling in-
terval, and QRS duration which merits early recogni- Conclusions
tion and treatment. Recognition of long-term side
effects of amiodarone has led to a major shift in pre- With the superiority of ICD in the prevention of SCD
vailing concepts among clinicians concerning choosing as well as advances in catheter ablation, the role of AADs
the right AAD. In the latest ESC guidelines, it is a class in the management of VAs has changed over time. They
III drug for the management of PVCs with normal LV continue to play a key role in the suppression of VA and
function where catheter ablation and other AADs are in preventing ICD shocks. Though amiodarone con-
the mainstay [14]. Artificial intelligence has been re- tinues to be the most used medication for VA sup-
cently used to localize PVCs from a 12-lead EKG and pression, other drugs like nonselective β-blockers and
newer research may expand its use in identifying sites class I agents are now increasingly used in special
as well as grading the lethality of VAs [47]. Newer populations with inherited arrhythmias. Cardiac im-
devices have been used to monitor QTc duration during aging modalities and artificial intelligence may help
drug loading and avoid the need for inpatient moni- open new avenues for the safe and more specialized use
toring as shown in Figure 3 [48]. Despite these of these agents.

128 Cardiology 2023;148:119–130 Apte/Kalra

DOI: 10.1159/000529670
 Conflict of Interest Statement Author Contributions
The authors have no conflicts of interest to declare.
N.A. and D.K.K. contributed equally to the manuscript. N.A.
was responsible for drafting the manuscript including collecting
Funding Sources references and making tables and figures. D.K.K. was responsible
The authors did not receive any funding for researching this article. for review and overall supervision.

References

1 Hiss RG, Lamb LE. Electrocardiographic 11 The Sicilian Gambit. A new approach to the 21 Watanabe H, van der Werf C, Roses-Noguer
findings in 122,043 individuals. Circulation. classification of antiarrhythmic drugs based F, Adler A, Sumitomo N, Veltmann C, et al.
1962;25(6):947–61. on their actions on arrhythmogenic mecha- Effects of flecainide on exercise-induced
2 Massing MW, Simpson RJ Jr, Rautaharju P, nisms. Task Force of the Working Group on ventricular arrhythmias and recurrences in
Schreiner PJ, Heiss G, Crow R, et al. Use- Arrhythmias of the European Society of genotype-negative patients with catechol-
fulness of ventricular premature complexes to Cardiology. Circulation. 1991;84(4):1831–51. aminergic polymorphic ventricular tachy-
predict coronary heart disease events and 12 Hodges M, Haugland JM, Granrud G, Conard cardia. Heart Rhythm. 2013;10(4):542–7.
mortality (from the Atherosclerosis Risk in GJ, Asinger RW, Mikell FL, et al. Suppression 22 Hyman MC, Mustin D, Supple G, Schaller RD,

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

Communities cohort). Am J Cardiol. 2006 of ventricular ectopic depolarizations by fle- Santangeli P, Arkles J, et al. Class IC antiar-
Dec;98(12), 1609–12. cainide acetate, a new antiarrhythmic agent. rhythmic drugs for suspected premature ven-
3 Bikkina M, Larson M, Levy D, Levy D. Circulation. 1982;65(5):879–85. tricular contraction-induced cardiomyopathy.
Prognostic implications of asymptomatic 13 Tamargo J, Caballero R, Gomez R, Valen- Heart Rhythm. 2018;15(2):159–63.
ventricular arrhythmias: the Framingham zuela C, Delpon E. Pharmacology of cardiac 23 Kim HK, Kim SS, Ki YJ, Park KH, Choi DH.
Heart Study. Ann Intern Med. 1992 Dec; potassium channels. Cardiovasc Res. 2004; Ventricular tachycardia in association with
117(12):990–6. 62(1):9–33. propafenone overdose. Acta Cardiol Sin.
4 Heckbert SR, Austin TR, Jensen PN, Floyd JS, 14 Zeppenfeld K, Tfelt-Hansen J, de Riva M, 2021;37(1):100–3.
Psaty BM, Soliman EZ, et al. Yield and con- Winkel BG, Behr ER, Blom NA, et al. 2022 24 Varro A, Elharrar V, Surawicz B. Effect of
sistency of arrhythmia detection with patch ESC Guidelines for the management of pa- antiarrhythmic drugs on the premature ac-
electrocardiographic monitoring: the multi- tients with ventricular arrhythmias and the tion potential duration in canine cardiac
ethnic study of atherosclerosis. J Electrocardiol. prevention of sudden cardiac death. Eur Purkinje fibers. J Pharmacol Exp Ther. 1985;
2018 Nov-Dec;51(6). 997–1002. Heart J. 2022;43(40):3997–4126. 233(2):304–11.
5 Refaat MM, Gharios C, Moorthy MV, 15 Hellestrand KJ, Bexton RS, Nathan AW, 25 Larson J, Rich L, Deshmukh A, Judge EC,
Abdulhai F, Blumenthal RS, Jaffa MA, et al. Spurrell RA, Camm AJ. Acute electrophysi- Liang JJ. Pharmacologic management for
Exercise-induced ventricular ectopy and ological effects of flecainide acetate on cardiac ventricular arrhythmias: overview of anti-
cardiovascular mortality in asymptomatic conduction and refractoriness in man. Br arrhythmic drugs. J Clin Med. 2022;11(11):
individuals. J Am Coll Cardiol. 2021;78(23): Heart J. 1982;48(2):140–8. 3233.
2267–77. 16 Su L, Xia X, Liang D, Wu S, Xu L, Xu T, et al. 26 Sanfilippo F, Corredor C, Santonocito C,
6 Patton KK. The riddle of nonsustained Effects of rhythm and rate-controlling drugs Panarello G, Arcadipane A, Ristagno G, et al.
ventricular tachycardia and sudden cardiac in patients with permanent his-bundle pac- Amiodarone or lidocaine for cardiac arrest: a
death. Circulation. 2010;122(5):449–51. ing. Front Cardiovasc Med. 2020;7:585165. systematic review and meta-analysis. Resus-
7 Scirica BM, Braunwald E, Belardinelli L, 17 Hellestrand KJ, Nathan AW, Bexton RS, citation. 2016;107:31–7.
Hedgepeth CM, Spinar J, Wang W, et al. Camm AJ. Electrophysiologic effects of fle- 27 Ortiz M, Martin A, Arribas F, Coll-Vinent B,
Relationship between nonsustained ventric- cainide acetate on sinus node function, Del Arco C, Peinado R, et al. Randomized
ular tachycardia after non-ST-elevation acute anomalous atrioventricular connections, and comparison of intravenous procainamide vs.
coronary syndrome and sudden cardiac pacemaker thresholds. Am J Cardiol. 1984; intravenous amiodarone for the acute treat-
death: observations from the metabolic effi- 53(5):30B–8B. ment of tolerated wide QRS tachycardia: the
ciency with ranolazine for less ischemia in 18 Echt DS, Liebson PR, Mitchell LB, Peters RW, PROCAMIO study. Eur Heart J. 2017;38(17):
non-ST-elevation acute coronary syndrome- Obias-Manno D, Barker AH, et al. Mortality 1329–35.
thrombolysis in myocardial infarction 36 and morbidity in patients receiving encai- 28 Gorgels AP, van den Dool A, Hofs A, Mul-
(MERLIN-TIMI 36) randomized controlled nide, flecainide, or placebo. The Cardiac leneers R, Smeets JL, Vos MA, et al. Com-
trial. Circulation. 2010;122(5):455–62. Arrhythmia Suppression Trial. N Engl J Med. parison of procainamide and lidocaine in
8 Huikuri HV, Tapanainen JM, Lindgren K, 1991;324(12):781–8. terminating sustained monomorphic ven-
Raatikainen P, Makikallio TH, Juhani Air- 19 Salvage SC, Gallant EM, Fraser JA, Huang tricular tachycardia. Am J Cardiol. 1996;
aksinen KE, et al. Prediction of sudden car- CLH, Dulhunty AF. Flecainide paradoxically 78(1):43–6.
diac death after myocardial infarction in the activates cardiac ryanodine receptor channels 29 Markel DT, Gold LS, Allen J, Fahrenbruch
beta-blocking era. J Am Coll Cardiol. 2003; under low activity conditions: a potential pro- CE, Rea TD, Eisenberg MS, et al. Procaina-
42(4):652–8. arrhythmic action. Cells. 2021;10(8):2101. mide and survival in ventricular fibrillation
9 Vaughan Williams EM. Classification of 20 van der Werf C, Kannankeril PJ, Sacher F, out-of-hospital cardiac arrest. Acad Emerg
antidysrhythmic drugs. Pharmacol Ther B. Krahn AD, Viskin S, Leenhardt A, et al. Med. 2010;17(6):617–23.
1975;1(1):115–38. Flecainide therapy reduces exercise-induced 30 Li DL, Cox ZL, Richardson TD, Kanaga-
10 Lei M, Wu L, Terrar DA, Huang CLH. ventricular arrhythmias in patients with sundram AN, Saavedra PJ, Shen ST, et al.
Modernized classification of cardiac antiar- catecholaminergic polymorphic ventricular Quinidine in the management of recurrent
rhythmic drugs. Circulation. 2018;138(17): tachycardia. J Am Coll Cardiol. 2011;57(22): ventricular arrhythmias: a reappraisal. JACC
1879–96. 2244–54. Clin Electrophysiol. 2021;7(10):1254–63.

Pharmacotherapy in Ventricular Cardiology 2023;148:119–130 129

Arrhythmias DOI: 10.1159/000529670
31 Mizusawa Y, Sakurada H, Nishizaki M, Hir- 38 Kheiri B, Barbarawi M, Zayed Y, Hicks M, 44 Kapa S, Gaba P, DeSimone CV, Asirvatham
aoka M. Effects of low-dose quinidine on Osman M, Rashdan L, et al. Antiarrhythmic SJ. Fascicular ventricular arrhythmias: path-
ventricular tachyarrhythmias in patients with drugs or catheter ablation in the management ophysiologic mechanisms, anatomical con-
Brugada syndrome: low-dose quinidine ther- of ventricular tachyarrhythmias in patients structs, and advances in approaches to
apy as an adjunctive treatment. J Cardiovasc with implantable cardioverter-defibrillators: management. Circ Arrhythm Electrophysiol.
Pharmacol. 2006;47(3):359–64. a systematic review and meta-analysis of 2017;10(1):e002476.
32 Shen T, Yuan B, Geng J, Chen C, Zhou X, randomized controlled trials. Circ Arrhythm 45 Curnis A, Salghetti F, Cerini M, Vizzardi E,
Shan Q. Low-dose quinidine effectively re- Electrophysiol. 2019;12(11):e007600. Sciatti E, Vassanelli F, et al. Ranolazine
duced shocks in Brugada syndrome patients 39 Ho DS, Zecchin RP, Cooper MJ, Richards therapy in drug-refractory ventricular ar-
with an implantable cardioverter defibrilla- DA, Uther JB, Ross DL. Rapid intravenous rhythmias. J Cardiovasc Med. 2017;18(7):
tor: a Chinese case series report. Ann Non- infusion of d-1 sotalol: time to onset of effects 534–8.
invasive Electrocardiol. 2017;22(1):e12375. on ventricular refractoriness, and safety. Eur 46 Chorin E, Hu D, Antzelevitch C, Hochstadt
33 Vitali Serdoz L, Rittger H, Furlanello F, Heart J. 1995;16(1):81–6. A, Belardinelli L, Zeltser D, et al. Ranolazine
Bastian D. Quinidine-A legacy within the 40 Cui G, Sager PT, Singh BN, Sen L. Different for congenital long-QT syndrome type III:
modern era of antiarrhythmic therapy. effects of amiodarone and quinidine on the experimental and long-term clinical data.
Pharmacol Res. 2019;144:257–63. homogeneity of myocardial refractoriness in Circ Arrhythm Electrophysiol. 2016;9(10):
34 Sethi KK, Sethi K, Chutani SK. J wave syn- patients with intraventricular conduction e004370.
drome: clinical diagnosis, risk stratification delay. J Cardiovasc Pharmacol Ther. 1998; 47 Zheng J, Fu G, Abudayyeh I, Yacoub M,
and treatment. J Atr Fibrillation. 2014;7(4): 3(3):201–8. Chang A, Feaster WW, et al. A high-precision
1173. 41 Shenthar J, Rachaiah JM, Pillai V, Chakali SS, machine learning algorithm to classify left

Downloaded from http://karger.com/crd/article-pdf/148/2/119/3966423/000529670.pdf by guest on 14 April 2025

35 Kaufman ES. Quinidine in short QT syn- Balasubramanian V, Chollenhalli Nanjappa and right outflow tract ventricular tachy-
drome: an old drug for a new disease. M. Incidence of drug-induced torsades de cardia. Front Physiol. 2021;12:641066.
J Cardiovasc Electrophysiol. 2007;18(6): pointes with intravenous amiodarone. Indian 48 Chung EH, Guise KD. QTC intervals can be
665–6. Heart J. 2017;69(6):707–13. assessed with the AliveCor heart monitor in
36 Schwartz PJ, La Rovere MT, Vanoli E. Au- 42 Connolly SJ, Hallstrom AP, Cappato R, patients on dofetilide for atrial fibrillation.
tonomic nervous system and sudden cardiac Schron EB, Kuck KH, Zipes DP, et al. Meta- J Electrocardiol. 2015;48(1):8–9.
death. Experimental basis and clinical ob- analysis of the implantable cardioverter de- 49 Kurtzwald-Josefson E, Yadin D, Harun-Khun
servations for post-myocardial infarction risk fibrillator secondary prevention trials. AVID, S, Waldman M, Aravot D, Shainberg A, et al.
stratification. Circulation. 1992;85(1 Suppl l): CASH and CIDS studies. Antiarrhythmics vs Viral delivered gene therapy to treat cate-
I77–91. implantable defibrillator study. Cardiac arrest cholaminergic polymorphic ventricular
37 Moss AJ, Zareba W, Hall WJ, Schwartz PJ, study hamburg . Canadian implantable de- tachycardia (CPVT2) in mouse models.
Crampton RS, Benhorin J, et al. Effectiveness fibrillator study. Eur Heart J. 2000;21(24): Heart Rhythm. 2017;14(7):1053–60.
and limitations of beta-blocker therapy in 2071–8. 50 Katz G, Shainberg A, Hochhauser E, Kurtz-
congenital long-QT syndrome. Circulation. 43 Belhassen B, Horowitz LN. Use of intrave- wald-Josefson E, Issac A, El-Ani D, et al. The
2000;101(6):616–23. nous verapamil for ventricular tachycardia. role of mutant protein level in autosomal
Am J Cardiol. 1984;54(8):1131–3. recessive catecholamine dependent poly-
morphic ventricular tachycardia (CPVT2).
Biochem Pharmacol. 2013;86(11):1576–83.

130 Cardiology 2023;148:119–130 Apte/Kalra

DOI: 10.1159/000529670