Cell Biochem Biophys

DOI 10.1007/s12013-015-0626-4

ORIGINAL PAPER

Cardiac Arrhythmias: Diagnosis, Symptoms, and Treatments

Du-guan Fu

Ó Springer Science+Business Media New York 2015

Abstract The cardiac arrhythmia is characterized by ir- premature atrial contractions and premature ventricular
regular rhythm of heartbeat which could be either too slow contractions occur in the heart beating process. The seri-
(\60 beats/min) or too fast ([100 beats/min) and can ousness of cardiac arrhythmias depends on the presence or
happen at any age. The use of pacemaker and defibrillators absence of structural heart disease. The atrial fibrillation
devices has been suggested for heart arrhythmias patients. (AF) is a benign arrhythmia. In patients, coronary heart
The antiarrhythmic medications have been reported for the disease or severe left ventricular dysfunction could cause a
treatment of cardiac arrhythmias or irregular heartbeats. heart failure or sudden cardiac death.
The diagnosis, symptoms, and treatments of cardiac ar-
rhythmias as well as the radiofrequency ablation, tachy-
cardia, Brugada syndrome, arterial fibrillation, and recent Symptoms of Cardiac Arrhythmias
research on the genetics of cardiac arrhythmias have been
described here. The symptoms of cardiac arrhythmias are complaints of
dizziness, palpitations, fast heart beating, and feeling of
Keywords Cardiac arrhythmias
Defibrillators
weakness which should be consulted with the family
Tachycardia
Radiofrequency ablation physician. More than 600,000 people in USA die every
year due to heart failure or sudden cardiac death as reported
in Statistics from Center for Disease Control and Preven-
Introduction tion (CDC), Cleveland Clinic Reports, OH, USA, 2014 [1].
About 50 % of heart patients die of sudden death due to
Cardiac arrhythmias are the abnormalities or perturbations cardiac arrhythmias but it can be controlled by an auto-
in the normal activation or beating of heart myocardium. matic external defibrillator device (AEDs) which can re-
The sinus node sends a depolarization wave over the atrium duce the mortality rate when used quickly within few
and depolarizing atrioventricular (AV) node propagating minutes after the first heart attack.
over His-Purkinje system and depolarizes ventricle in
systematic way. There are many types of cardiac arrhyth-
mias or abnormal heart beating. The normal rhythm of The Pathogenesis of Arrhythmias
heart is called as sinus rhythm which can be disturbed
through failure of automaticity as a sick sinus syndrome The pathogenesis of cardiac arrhythmias has three basic
(SSS) or as an inappropriate sinus tachycardia. The mechanisms: (1) the enhanced or suppressed automaticity,
(2) triggered activity, or (3) re-entry. The automaticity is a
natural property of all myocytes. The various factors which
D. Fu (&) may suppress or enhance automaticity are heart ischemia,
Department of Cardiology, Xiangyang Hospital Affiliated to
scarring, electrolyte disturbance, heart medications, old age,
Hubei University of Medicine, Xiangyang 441000, Hubei,
People’s Republic of China and other factors. The suppression of automaticity of the
e-mail: [email protected] sinoatrial (SA) node can result in sinus node dysfunction and

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 Cell Biochem Biophys

in SSS which is a common indication for permanent pace- Treatment of Arrhythmias

maker (PPM) implantation. The enhanced automaticity can
result in multiple arrhythmias for both atrial and ventricular The treatments of arrhythmias are described in The New
arrhythmias. The triggered activity which usually occurs York Times, July 23, 2014 [3] and these treatments in-
after earlier and delayed depolarizations initiates sponta- clude: electrical ‘‘shock’’ therapy (defibrillation or car-
neous multiple depolarizations, and results in precipitating dioversion), and implanting of pacemaker in the chest of
ventricular arrhythmias. Example includes ventricular ar- the patient. The antiarrhythmic drugs may be used to pre-
rhythmias caused by Digitalis drug toxicity. The re-entry is a vent an arrhythmia from happening again, and to keep
common mechanism of arrhythmogenesis which includes heart rate from becoming too fast or too slow. Some drugs
bidirectional conduction and unidirectional block. The mi- may have adverse side effects so these should be taken with
cro level re-entry occurs with VT from conduction around caution under supervision of a physician. The other treat-
the scar of myocardial infarction (MI), and macro level re- ments include cardiac ablation for heart rhythm problem,
entry occurs via conduction through Wolff–Parkinson– implantable cardiac defibrillator to control heart failure,
White (WPW) syndrome concealed accessory pathways. and pacemaker device when heart is beating irregularly. It
sends a signal to heart that makes it beat at an accurate and
normal pace.
Signs and Symptoms of Cardiac Arrhythmias

There are some signs and symptoms of cardiac arrhythmias Pacemakers and Defibrillators
such as loss of consciousness and more severe symptoms
occur in the presence of structural heart disease, such as a The implantation of a PPM requires specific levels of
sustained monomorphic VT in normal heart and several LV evidence and indications based on American College of
dysfunctions. More symptoms for arrhythmias include Cardiology and American Heart Association (ACC/AHA)
dizziness, fluttering, pounding, shortness of breath, chest guidelines [4]. Class I and Class II indications are appro-
pain, and forceful extra heart beats. Arrhythmia patients are priate for the implantation of a PPM. The correlation of
observed after checking their peripheral pulses. The tachy- symptoms with underlying bradyarrhythmias or heart block
cardias, fast heart beatings, are accompanied by chest pain or is required. The implantable ICD is indicated for sustained
discomfort, diaphoresis, neck fullness, or vasovagal type of VT or VF, survivors of sudden cardiac death, Antiar-
response with syncope, diaphoresis, or nausea. The isolated rhythmics Versus Implantable Defibrillators (AVID) trial,
or occasional premature beats suggest PACs or PVCs and are secondary prevention [5] or inducible, sustained,
benign in the absence of structural heart disease. monomorphic VT Multicenter Automatic Defibrillator
Implantation Trial (MADIT I), and primary prevention [6,
7].
Diagnosis of Arrhythmias

The diagnosis of cardiac arrhythmias is by observation of Defibrillators

blood pressure, ECG and irregular heart beat (slower or
faster), and feeling of weakness, fatigue, dizziness and not These can be of single chamber or dual chamber and may
very active at daily routine work. The values of ventricular have rate responsiveness. The results of the dual chamber
electrocardiogram recordings are described in the diagnosis and VVI implantable defibrillator (DAVID) studies have
of arrhythmias in Diagnostic study [2]. Sixteen heart pa- shown that dual-chamber pacing ICDs in patients with de-
tients were implanted with an antitachycardia pacemaker creased LV function lead to an increased incidence of con-
cardioverter-defibrillator (ICD) device that is capable of gestive heart failure (CHF) and increased mortality [8]. The
storing ventricular electrocardiograms before and after presumed mechanism is by creating a functional left bundle
delivery of device shock therapy. Three patients experi- branch block (LBBB), which can lead to cardiac desyn-
enced minimal symptoms. The careful analysis of ECG chronization and heart failure. In contrast, restoring cardiac
during supraventricular and ventricular rhythms was per- resynchronization with biventricular pacing can improve
formed during in-hospital testing (AF, polymorphic ven- CHF symptoms and that leads to an explosion of referrals to
tricular tachycardia and rate-sensing lead disruption), implant patients with Classes II to IV CHF and severe LV
respectively. Therefore, the ability to store ventricular ECG dysfunction [9]. For the primary prevention of sudden death
before shock therapy represents a major advancement in in patients with severe LV dysfunction, normal intact sinus
the management of patients who receive an electrical de- node, AV node, and conduction, and no perceived or an-
vice to treat ventricular tachyarrhythmia (VTA). ticipated indication for pacing, the preferred ICD device is a

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single-chamber device (ventricular paced and inhibited pathway is in the left ventricular free wall, but it also can
(VVI) pacemaker). Dual-chamber ICDs should be reserved be posteroseptal or right sided. RFA has been successful in
for patients with an abnormal SA or AV node or conduction ablating and curing WPW. The success rate is 97 % and
system or those with frequent supraventricular arrhythmias, has been safely achieved in many centers. For symptomatic
such as AF, to avoid shocks secondary to rapid ventricular WPW, particularly in young patients, RFA is considered to
responses. When dual-chamber pacing is required, and the be the treatment of choice.
LV is severely impaired, consideration should be given to a Radiofrequency ablation (RFA) has also been extremely
biventricular ICD. useful in curing typical atrial flutter, which is identified by
an atrial rate of 240 beats/min or higher and characteristic
negative sawtooth flutter waves were identified on the
Radiofrequency Ablation ECG, typically in inferior leads (II, III, and aVF). The
mapping studies have shown that typical flutter occurs with
Radiofrequency catheter ablation (RFA) has been an ex- a counter clockwise rotation of atrial activation descending
cellent advancement in the treatment of cardiac arrhyth- on the right atrial free wall, traversing the isthmus (zone
mias [10–12]. RFA has provided an opportunity to care for between the coronary sinus orifice and tricuspid leaflet) and
a specific cardiac disease. Introduced over 20 years ago as ascending the intra-atrial septum. Disruption of conduction
DC ablation and in 1980 with radiofrequency, RFA has over the isthmus by RFA can successfully eliminate the
proved to be a safe and cost-effective treatment for specific potential for typical flutter. However, 25 % of patients
cardiac arrhythmias such as atrioventricular nodal re-entry continued to have atrial tachyarrhythmias, especially AF.
tachycardia (AVNRT), orthodromic reciprocating tachy- The RFA is an acceptable therapy of first choice for
cardia associated with WPW syndrome and concealed ac- symptomatic atrial flutter.
cessory pathways, normal heart VT (particularly right
ventricular outflow tract tachycardia or fascicular tachy-
cardia), and atrial flutter [10, 11, 13]. RFA can also provide Antiarrhythmic Medications
adjuvant therapy for ischemic VT when the patients are
experiencing frequent ICD shock or failing antiarrhythmic The Cardiac Arrhythmia Suppression Trial study (CAST)
therapy. The pulmonary vein isolation is a treatment option changed the use of antiarrhythmic medications [16]. CAST
for symptomatic, drug refractory, paroxysmal, or persistent was designed to test the hypothesis that antiarrhythmic
AF is an acceptable method and is undergoing clinical medication suppression of PVCs and non-sustained VT
study [14]. However, rate control and chronic antico- would improve mortality in patients following an MI who
agulation are acceptable alternatives for patients with AF had decreased LV function. The preferred medications
as the results of Atrial Fibrillation Follow up Investigation Moricizine, Flecainide, and Encainide were known to have
of Rhythm Management (AFFIRM) study [15]. potent ventricular arrhythmia suppression properties. How-
Macro re-entry tachycardia, known as orthodromic re- ever, CAST demonstrated an increase in mortality in patients
ciprocating tachycardia (ORT) or AVRT, reciprocating treated with antiarrhythmic drugs compared with placebo.
tachycardia, occurs when the AV node is used in an ante- Perhaps the increased mortality rate resulted from the
grade direction and the accessory pathway is used in a proarrhythmic effects of these drugs, especially in the pres-
retrograde direction. AVRT is a narrow complex tachy- ence of ischemia and LV dysfunction [17]. Therefore, type
cardia, but it may have small retrograde P waves visible 1C drugs are contra-indicated in patients with CAD and is-
between the QRS and T waves. When the accessory chemia. There is a concern that increased mortality could
pathway is used in an antegrade direction, ART, antidromic occur with other antiarrhythmics, especially when adminis-
reciprocating tachycardia, a wide complex tachycardia tered for relatively benign arrhythmias (e.g., AF, PVCs).
occurs, which mimics VT. AF is common with WPW Quinidine showed to increase mortality when administered
syndrome, a constant retrograde re-entry into the atrium to patients with AF [18].
during ventricular depolarization. Because of the potential The Vaughn Williams classification of antiarrhythmic
for rapid conduction over an accessory pathway with AF medications is as shown in Chaudhry et al. [17]. The class 1,
and WPW, caution must be taken with AV nodal-blocking sodium channel blockers; class 1A, depresses phase 0 of
agents, digoxin, and calcium channel blockers. Although action, delays conduction, and prolongs repolarization—
rare, AF with rapid ventricular response over an accessory phase 3 or 4 (Quinidine, Procainamide, Disopyramide; class
pathway can initiate ventricular fibrillation, leading to a 1B, little effect on phase 0 of action potential in normal
sudden death. The acute treatment of AF and WPW con- tissues, depresses phase 0 in abnormal tissues, shortens
sists of cardioversion and occasionally intravenous pro- repolarization or little effect (Lidocaine, Tocainide, Mex-
cainamide. The most common location for an accessory iletine, Diphenyl-hydantoin); class 1C, depresses phase 0 of

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action potential, slows conduction in normal tissues (Fle- attention was given on the potential for ICD malfunction or
cainide, Propafenone, Moricizine); class 2, beta-adrenergic device failure [20, 21]. The manufacturers have recognized
blocking agents (Acebutolol, Atenolol, Bisoprolol, Carve- potential design flaws, such as premature battery depletion,
dilol, Metoprolol, Nadolol, Pindolol, Propranolol); class 3, oversensing or undersensing of ventricular arrhythmias,
prolongs action potential duration by increasing repolar- and crosstalk. Since the introduction of the defibrillator
ization and refractoriness (Amiodarone, Sotalol, Bretylium, nearly 30 years ago, these devices have been extremely
Dofetilide, Azimilide, Ibutilide); class 4, calcium channel reliable. The failure rates are particularly low. However,
blockers (Diltiazem, Verapamil); and others (Digoxin, the use of ICDs has led to an awareness of manufacturing
Adenosine). with no defects and their incidence has remained relatively
After the CAST study, several reports have confirmed low. Many potential device recalls can be managed con-
the proarrhythmic effects of antiarrhythmic medication servatively with expedited and intensified follow up of
when used capriciously, which led to specific guidelines for battery status and the use of home telephonic monitoring
the use of antiarrhythmic medications, especially those modalities, such as CareLink (www.medtronic.com and
that, prolong the QT interval and increase proarrhythmia. new tachycardia therapy by Rajamani et al. [21]).
Usually, types IA and III drugs are initiated in the hospital The evaluation of cardiac arrhythmias started with
with telemetry monitoring. Type IC agents, are relatively documentation of the arrhythmia type and investigation for
safe when used in a normal heart. underlying heart disease. The RFA is acceptable as first-
Similarly, Amiodarone because of its longer half-life line therapy for many arrhythmias, including SVTs, such as
(43 days to few months) and low incidence of proar- WPW, AVNRT, and atrial flutter. The ICDs should be
rhythmia, can be initiated at low doses in an outpatient considered for any arrhythmia patient with an EF of 35 %
setting in the absence of severe LV dysfunction or brady- or lower. The ECG and pacemaker devices are very useful
cardia. Based on the results of the CAST study, the Food for the arrhythmias patients. Some useful readings have
and Drug Administration (FDA), USA, and pharmaceutical also been mentioned [22–25].
industries took measures to ensure appropriate prescription
practices and credentials of physicians when the new an-
tiarrhythmic medication, Dofetilide (Tikosyn, was released Recent Research on Arrythmia
to be used for AF patients.
New research in heart diseases has shown that air pollution
is associated with specific cardiovascular diseases and even
Normal Heart Ventricular Tachycardia death [26]. The deaths by heart failure make up to 10 % of
all cardiovascular diseases and are responsible for 30 % of
The sustained and non-sustained VT can occur in the absence the cardiovascular deaths related to SO2, CO2, and NO2 air
of structural heart disease, so called normal heart VT. In pollution. The recent advances have been made in clinical
general, the prognosis is good, with a low risk for sudden cardiac electrophysiology and pacing and mechanism for
cardiac death. The examples include right ventricular out- AF for detection and treatment of heart diseases [27]. The
flow tract (RVOT) and left ventricular outflow tract (LVOT), alternative options have been suggested for patients with
VT, fascicular VT, idiopathic left VT, repetitive monomor- AF risk or thromboembolic risk by introducing a new oral
phic VT, and sinus of Valsalva VT [19]. The treatment is anticoagulant and use of catheter ablation of symptomatic
usually with beta blockers or calcium channel blockers and if AF. Another new area of cardiac arrhythmias and pacing is
refractory, RFA treatment is aimed at symptom suppression in the use of cardiac resynchronization therapy (CRT) for
in patients. the treatment of patients with heart failure. The CRT
confers a survival advantage in heart patients with severe
heart failure and improves symptoms and response. The
Brugada Syndrome new research has also been made of sudden cardiac death
of patient and implantable cardioverter defibrillators for
Brugada syndrome is a relatively rare cause of VT and epidemiological and clinical study, risk stratification, and
fibrillation. It is characterized by an abnormal ECG ex- management.
hibiting a right bundle branch block pattern and ST seg- Recent studies on heart arrhythmias and innovations
ment elevation in the precordial leads. The treatment have been reported by Kuck and Hindricks [28]. The recent
requires implantation of an ICD in patients with syncope advances in the management of AF, AF, and new treat-
and complex ventricular arrhythmias. There was a con- ments and technology have been shown to improve the
siderable debate on the applicability of MADIT-II in health diagnosis and treatment of arrhythmias. The implantable
care system to qualify for a defibrillator. Recently, media electronic devices have been mentioned and implantable

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cardioverter defibrillator-shocks, and CRT has been de- ethnically distinct populations, ciseQTL (expression quan-
scribed which will help to improve the quality of care of titative trait loci) mapping and functional validation of ge-
heart failure and cardiac arrhythmias patients. The cardiac netic data for heart subjects. The four novel loci were
arrhythmias can be treated using medications and there are identified in individuals of Europe descent near the genes
three classes of drugs useful for heart rhythms [29]. The NEURAL. The novel gene loci were also identified near
antiarrhythmic drugs change the electrical properties of NEURL in Japanese people, Top single-nucleotide poly-
cardiac tissues and spread these signals across the heart for morphisms or their proxies were identified as cis-eQTLs for
beating. The tachycardias, rapid heart rate, are related to the genes CAND2 (P = 2.6 9 10-19), GJA1 (P = 2.66 9
abnormal electrical signals. The drugs which improve the 10-6), and TBX5 (P = 1.36 9 10-5). The results with Ze-
electrical signals of heart are used for arrhythmia. Some brafish orthologs of NEURL and CAND2 showed prolon-
drugs have side effects, so care should be taken for an- gation of atrial action potential duration (17 and 45 %,
tiarrhythmic drugs. The commonly used antiarrhythmic respectively). The five novel gene loci have been identified
drugs are Amiodarone (Cordarone, Pacerone), Sotalol for AF. Results of the diversity of genetic pathways in AF
(Betapace), Propafenone (Rhythmol), and Dronedarone will provide the new molecular targets for future medical and
(Multaq). Amiodarone drug is mostly used for arrhythmia pharmacological investigations of heart diseases.
patients. The beta blockers reduce the risk of sudden death
by blocking effect of adrenaline on heart muscle, thus re-
ducing fatal arrhythmias. The Statins also reduce the risk of
heart failure or consumption of omega-3 fatty acids, but References
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