Ventricular Arrhythmias: From the Electrophysiology Laboratory to Clinical Practice. Part II

17 Pages·2012·0.69 MB·English

Hellenic J Cardiol 2012; 53: 217-233
RReevviieeww AArrttiiccllee
Ventricular Arrhythmias: From the
Electrophysiology Laboratory to Clinical Practice.
Part II: Potentially Malignant and Benign
Ventricular Arrhythmias
Konstantinos a. Gatzoulis1, stefanos archontaKis1, Polychronis Dilaveris1,
Dimitrios tsiachris1, Petros arsenos1, sKevos siDeris2, christoDoulos stefanaDis1
1First University Department of Cardiology, University of Athens, 2State Cardiology Division, Hippokration General
Hospital, Athens, Greece
V
Key words: Risk entricular arrhythmias remain of ventricular arrhythmias, ranging from
stratification a common problem in everyday the benign to potentially malignant.
for sudden
practice for the clinical cardiol-
cardiac death,
ogist.1 Most concerns are related to the
electrophysiological Potentially malignant ventricular
study, malignant fact that sustained ventricular tachyar-
arrhythmias
ventricular rhythmias represent a major cause of sud-
tachyarrhythmias,
den cardiac death (SCD) and morbidity In this group of patients, the study of
automatic
in patients with various types of heart dis- the cardiac substrate is fundamental. At-
implantable
cardioverter ease, and in some cases even in patients tempts to empirically suppress ventricu-
defibrillators. with structurally normal hearts. There- lar arrhythmias, without any further risk
fore, risk stratification should be among stratification, by means of potent antiar-
the first priorities for all patients present- rhythmic medication have failed or, as
ing with ventricular arrhythmias. Recent in the case of amiodarone, have shown
research developments and technological only marginal benefits.3-9 It is thus rea-
Manuscript received:
achievements have resulted in a remark- sonable to suggest that all patients who
October 1, 2010;
able increase in the number of diagnos- present with complex ventricular arrhyth-
Accepted:
April 18, 2011. tic and prognostic tools for non-invasive mias should receive a complete assess-
risk stratification, providing a multitude ment using all available electrophysiologi-
of echocardiographic and electrocardio- cal means, non-invasive and/or invasive, in
Address:
graphic markers. On the other hand the order to identify those who would benefit
Konstantinos A
Gatzoulis electrophysiology laboratory provides us from the administration of the appropri-
with great opportunities in terms of com- ate antiarrhythmic therapy, pharmacologi-
P.O. Box 175 pleting the risk stratification and imple- cal or not. Our strategy should be individ-
19009 Drafi Attikis
mentation of a number of interventional ualised, according to the nature and the
Athens, Greece
e-mail: therapies, such as catheter ablation and severity of the underlying structural heart
[email protected] implantation of the life-saving automat- disease.
ic implantable cardioverter defibrillators
(AICD).2 In this review we present the
Coronary heart disease (CHD)
different electrophysiologically-guided ap-
proaches for investigating the great variety It has previously been shown by many
(Hellenic Journal of Cardiology) HJC • 217
K.A. Gatzoulis et al
studies that risk factors predicting the development plied.16,17,24-26 Attempts to introduce scoring systems
of severe ventricular arrhythmias can be determined that include clinical, laboratory and electrocardio-
from medical history, non-invasive electrocardiogra- graphic parameters (e.g. New York Heart Associa-
phy, and echocardiography. These risk factors include tion, NYHA class >II, QRS duration >120 ms, age
a history of multiple myocardial infarctions (MI), syn- >70 years, presence of atrial fibrillation, and blood
cope, complex ventricular ectopy, activation of the urea nitrogen >9 mmol/L) have been made, but ex-
sympathetic nervous system, detection of sites of slow perience is still limited.27,28
ventricular conduction or ventricular conduction ab- However not all post-MI patients with LVEF
normalities, presence of ventricular aneurysm, and ≤30% are at risk of SCD. It is estimated that 25%
left ventricular (LV) dysfunction. The more the risk of this patient population are at low risk, based on
factors revealed in non-invasive studies, the higher the absence of complex ventricular ectopy, inducibil-
the probability of either triggering sustained ventric- ity of VT/VF on PVS, prolongation of the QRS com-
ular tachyarrhythmia during an electrophysiological plex, and symptoms of advanced congestive heart fail-
study (EPS) and/or the patient presenting with such ure.29,30 In such patients the risk stratification pro-
an episode during the next 3 years of follow up.10-14 cess, including PVS, could be repeated periodically,
Based on the design and the results of 3 out of 4 every 2 to 3 years, given its high negative predictive
major primary trials for the prevention of SCD with an value. A high negative predictive value has also been
AICD, we know that post-infarction patients with non- claimed when no late potentials are found on the
sustained ventricular tachycardia (VT) and LV dys- signal-averaged ECG (SAECG), whereas the posi-
function (LV ejection fraction, EF≤40%) in whom VT tive predictive value is relatively low (<30%).31 The
and/or ventricular fibrillation (VF) is induced by pro- SAECG is thus considered a strong predictor of ar-
grammed ventricular stimulation (PVS) have a bet- rhythmic death and total mortality. Most of these
ter life expectancy when treated with an AICD (MA- studies excluded post-MI patients with significant
DIT-I, MUSTT).11,15 Furthermore, even the simple prolongation of the unfiltered QRS complex on the
presence of significant LV dysfunction (LVEF≤30%) standard 12-lead ECG,31-36 a condition frequently
defines a high risk group of post-MI patients who met among high-risk post-MI patients with poten-
may also benefit from AICD implantation (MADIT tially malignant ventricular arrhythmias. There is ev-
II).16-18 In contrast, when coronary surgical revascu- idence that late potentials could be identified even
larisation is performed in post-MI patients associ- among these patients, provided that modified crite-
ated with LV dysfunction, with or without the pres- ria are applied. When non-conventional criteria of
ence of “soft” criteria of late potentials, there is no a very long filtered QRS duration (fQRS≥145 ms)
additional benefit from AICD implantation (CABG- with a long low amplitude signal in its terminal por-
PATCH).19 Thus, before we risk stratify the post-MI tion (LAS≥55 ms) and a significant depression of its
patient with the AICD in mind, we should first ex- voltage (RMS≤17.5 μV) are found, there is a high
haust all coronary revascularisation procedures avail- likelihood of inducing VT on PVS.36 A series of stud-
able in order to reduce coronary ischaemia and po- ies demonstrated a very high negative predictive val-
tentially improve the LV function. There is evidence ue for predicting ventricular arrhythmias for micro-
to support the late application of the risk stratifica- volt T-wave alternans (MTWA) in the post-MI (and
tion approach after the acute MI phase. Indeed, there non-CHD) population, regardless of the severity of
was no additional AICD benefit from the early de- LV dysfunction.37-40 We previously demonstrated that
vice implantation in the first month post-MI (DYNA- an inverse spatial QRS-T angle circadian variation is
MIT, IRIS).20-22 However in a recent retrospective re- associated with an adverse outcome in post-MI pa-
view of the MUSTT trial with EP-guided selection of tients, whereas a normal pattern is associated with a
AICD recipients, the risk of arrhythmic death did not favourable outcome.41 However, the prognostic value
vary as a function of time from the most recent MI.23 of heart rate variability, baroreflex sensitivity, heart
The LVEF has emerged as the simplest and most rate turbulence, and deceleration capacity of heart
important risk stratifier after the results of the MA- rate, which reflect the function of the autonomic ner-
DIT-II trial. Until more reliable tools for identifying vous system and of repolarisation parameters such as
a high risk for SCD are recognised, a low threshold QT dispersion, QT dynamicity and QT variability, re-
for AICD implantation for primary prevention in pa- mains controversial.16,17,24,25
tients with significant LV dysfunction should be ap- It should be mentioned that 2 out of 3 SCD vic-
218 • HJC (Hellenic Journal of Cardiology)
Ventricular Arrhythmias
tims with CHD have LVEF≥35%.28-30 Among post- The cost effectiveness of AICD therapy for the
MI patients with no severe LV dysfunction (LVEF in primary prevention of SCD in the post-MI patient
the 30% to 40% range) or even mild LV dysfunction has been a matter of discussion.49,50 When the device
(LVEF≥40%), one can meet patients at increased is used based on more stringent risk stratifiers, includ-
risk of SCD when indices such as non-sustained VT, ing PVS induction of VT/VF (MADIT-I, MUSTT pa-
inducibility of sustained ventricular tachyarrhythmia tient population) with the concurrent presence of
on PVS and/or prolongation of the QRS complex are complex ventricular ectopy and/or late potentials, the
present. Furthermore, beyond the LVEF there are incidence of appropriate AICD activation during the
a number of other non-invasively derived ECG in- short-term follow up is high.10,32,51 In contrast, the
dices, including heart rate variability, QT duration, corresponding incidence of appropriate AICD acti-
c
late ventricular potentials, and T-wave alternans, all vation is lower among the MADIT-II patient popula-
of which have been associated with an increased risk tion, especially when no late potentials or significant
of SCD.42-45 These additional non-invasive ECG risk QRS prolongation are detected.52 It could be argued
stratifiers have a low positive predictive value when that the device therapy can safely be postponed un-
examined alone, and thus have not been thoroughly til the repeat risk stratification approach identifies
investigated in prospective primary prevention AICD a higher risk among post-MI patients with LV dys-
trials. However, the positive predictive value is mark- function in whom no significant ventricular ectopy,
edly increased in subpopulations of post-MI patients QRS prolongation, late potentials, T-wave alternans
when multiple risk factors are present.20,46 In a re- or inducible sustained ventricular arrhythmias are
cent observational study of 1041 post-MI patients found. Provided that the underlying CHD remains
with well preserved LVEF≥40% (average 55 ± 10%), stable, the PVS could be repeated after 3 years if in
the incidence of non-invasively derived ECG indi- the meantime no additional non-invasive risk strati-
ces of risk, such as non-sustained VT, late potentials fiers emerge. This strategy may be more realistic in
and T-wave alternans, was estimated at about 10%.47 a world basis application given the economic and lo-
The presence of such risk factors was associated with gistic constraints, as well as a non-insignificant inci-
a higher incidence of major arrhythmic events dur- dence of late complications associated with the cur-
ing the long-term follow up. It is unknown how many rent AICD technology as it is applied today.53 Indeed,
of these post-MI patients would have had inducible AICD research and technology has a long way to go
VT/VF on EPS. Other electrocardiographic predic- before it can be uniformly applied to lower risk CHD
tors of cardiovascular events and SCD recently iden- patients. The devices have to be markedly reduced in
tified in this group of patients include the fragment- size and weight, have to be of longer duration, limit-
ed QRS complexes (notched QRS complexes unre- ing the need of replacement, to be smarter in recog-
lated to bundle-branch block) and early repolarisa- nising truly life-threatening ventricular arrhythmias;
tion (defined as an elevation of the QRS-ST junction the electrodes have to be smaller in size and more re-
of at least 0.1 mV from baseline in inferior or lateral sistant to time, and the risk of device-related infec-
leads), respectively.44 Indices of autonomic function tion has to be better controlled.
(heart rate variability, baroreflex sensitivity, heart
rate turbulence) may also predict VT/VF.44 Recent-
Idiopathic hypertrophic cardiomyopathy (IHCM)
ly, a scoring system was proposed for patients with
stable CHD and relatively preserved LVEF (>40%), Sudden death accounts for 50% to 70% of deaths as-
based on a number of clinical factors predicting SCD sociated with IHCM and can potentially affect any-
risk.44,48 Induction of VT or VF with PVS is a stron- one with the disease, although it is more common
ger predictor of risk for ventricular tachyarrhythmias in younger age groups.54,55 Thus, a non-invasive risk
in patients with well preserved, than in those with stratification strategy is an issue of fundamental clini-
moderately to severely reduced ventricular function.26 cal importance and should be adopted for every pa-
Although it is unknown whether AICD therapy may tient with this entity, especially in the young. More-
offer a significant survival benefit in such CHD pa- over, there is a proven high impact of protection of-
tients, one can argue to follow a more aggressive risk fered by AICDs to high-risk individuals with IH-
stratification approach, including PVS, in all of these CM.56-61
patients, implementing a device in those with induc- Major risk factors associated with higher rates
ible sustained ventricular tachyarrhythmias. of SCD have been identified; however, there are
(Hellenic Journal of Cardiology) HJC • 219
K.A. Gatzoulis et al
still doubts regarding the individual predictive val- predictors present, the higher the risk. Individuals
ue of each of them and so risk stratification has not with one marker are considered to be at intermediate
yet been completely systematised.62 Additionally, it risk, with an annual incidence of sudden death rang-
seems that there is an association of certain genet- ing from 1% to 1.5%, whereas the presence of two or
ic defects with SCD, even when the presence of hy- more markers increases the annual mortality rate to
pertrophy is minimal or absent.55 Risk predictors in- more than 3%.69 The group of patients manifesting
clude: the lowest risk for SCD (less than 1% per year) con-
a. The detection of complex ventricular arrhythmias sists of adults in NYHA functional class I/II, without
on ambulatory electrocardiography. The risk for a family history of SCD, who do not present with syn-
SCD is higher with frequent, repetitive and pro- cope, non-sustained VT on 24-hour Holter monitor-
longed episodes, whereas when sporadic and tran- ing, or abnormal blood pressure response during ex-
sient the prognosis is benign. A high negative and ercise, and who additionally exhibit a pressure gradi-
a low positive predictive value is suggested, with ent ≤30 mmHg, maximum LV wall thickness ≤20 mm
a favourable prognosis and mortality rates lower and left atrial diameter ≤45 mm.55 These patients can
than 1.5% per year in asymptomatic patients with be strongly reassured. In individuals at low or inter-
brief and infrequent episodes of non-sustained VT mediate risk for SCD, the risk stratification process
on 24-hour ECG ambulatory monitoring.63 On the should be repeated every 3-5 years.
other hand, children and young adults rarely have Other markers related to a high risk for SCD in
ventricular arrhythmias, but when these are pres- patients with IHCM are: myocardial ischaemia, ob-
ent the positive predictive value is high.64 struction of the LV outflow tract, paroxysmal atrial fi-
b. A history of aborted SCD defines the clinical brillation, conduction system disease, accessory path-
group with the highest risk for SCD, since the way, and over-activation of the sympathetic nervous
possibility to develop a new sustained VT/VF system.64 The predictive value of markers such as the
episode is as high as 10% per year.58 presence of late potentials on SAECG, heart rate
c. A history of syncope, which might be due to ven- variability, and QT dispersion has been debated.64
tricular or supraventricular tachy- or bradyar- Additionally, other risk factors, such as fractionation
rhythmias, has been recognised as an indepen- of paced RV electrograms, late gadolinium enhance-
dent risk factor for SCD.65,66 Syncope associated ment on magnetic resonance, and genotyping, have
with massive LV hypertrophy usually requires been investigated, but to date the results are contra-
prophylactic treatment, especially in the young.58 dictory or preliminary.70
d. A family history of SCD in first-degree family Implantation of AICDs in patients with IHCM is
members under 40 years old.67 a safe and effective preventive therapy marked with a
e. Excessive hypertrophy of the interventricular class I indication for secondary and class IIB for pri-
septum (>30 mm). An association between the mary prevention.58,71-73 The criteria used for AICD
echocardiographically determined extent of LV implantation are still empirical, based on clinical ex-
hypertrophy and mortality has been identified. perience. Thus, it has been currently suggested that
In a later study, however, the risk of SCD and an AICD should be implanted for primary preven-
AICD activation appears to depend more on tion in cases where two or more of the previously de-
the number of risk factors for SCD than on the scribed risk factors are present.54,55,64,69 There is no
severity of hypertrophy alone.68 In very young real consensus regarding patients with just one risk
patients, the risk is higher and justifies the factor and treatment decisions should thus be individ-
implantation of an AICD.68 ualised, considering the person’s age, the quantitative
f. An abnormal blood pressure response to exer- aspects of the risk factor involved, and the desires of
cise testing is associated with SCD, especially in the fully informed patient.55,73 Even a single marker
young individuals, where a high negative predic- of high risk may represent sufficient evidence to jus-
tive value is reported. However, when it is an iso- tify prophylactic AICD insertion in selected patients
lated abnormality, not associated with other risk with IHCM.72-74 Interestingly, a recent study showed
markers, no prophylactic treatment is required.55 that percutaneous alcohol septal ablation, a relatively
The probability of SCD is significantly higher new therapeutic strategy in IHCM, results in a trans-
when multiple risk factors are detected during non- mural scar in the hypertrophied proximal ventricular
invasive assessment and, in general, the more the risk septum and actually increases the risk for SCD, given
220 • HJC (Hellenic Journal of Cardiology)
Ventricular Arrhythmias
that AICD shocks were 4-fold more common com- ate activation rate for the primary prevention of SCD
pared to surgical myectomy.73 is lower than in other disease states such as CHD
The role of the EPS in IHCM is under investiga- and idiopathic dilated cardiomyopathy (Figure 1).58
tion and still remains a matter of debate, with older Whether PVS results might have improved the selec-
studies supporting an excellent long-term prognosis tion process of those IHCM patients who will get the
in cases where sustained ventricular tachyarrhythmias most from the AICD therapy remains unknown.
are not induced.57 It can be used in borderline cases
with one risk factor present, such as non-sustained
Idiopathic dilated cardiomyopathy (IDCM)
VT, history of unexplained syncope, family history of
SCD, or an abnormal response to exercise. Induction The risk of SCD in patients with IDCM is known to
of sustained ventricular arrhythmias on PVS could fa- be significant.17 A risk stratification approach, how-
cilitate the decision-making process for the AICD im- ever, that would include the history, electrocardio-
plantation. It could also be useful in cases where per- graphic and echocardiographic findings has not been
manent antibradycardia pacing is considered due to sufficiently investigated and evaluated in large pro-
coexisting sinus node dysfunction or/and significant spective trials.
conduction defects. The presence of complex ventricular arrhythmias,
It should be mentioned that AICD therapy in such as non-sustained VT in 24-hour ambulatory
high risk IHCM patients has not been tested in a pro- ECG monitoring, is common in patients with IDCM
spective controlled fashion. Based on a multi-centre and has been associated not only with a higher risk
retrospective collection of cases, we know that AICD for SCD but also with an increased overall mortali-
implantation is effective for subjects considered as ty.75,76 Moreover, it has been reported that LVEF is a
“high-risk”, although the long run AICD appropri- significant risk predictor for severe arrhythmias.26,75,77
Figure 1. Ventricular tachycardia recorded during interrogation of an automatic implantable cardioverter defibrillator (AICD) in a patient
with idiopathic hypertrophic cardiomyopathy. Interrogation of an AICD in a 14-year-old patient with idiopathic hypertrophic cardiomy-
opathy and multiple risk factors, who underwent device implantation for the primary prevention of sudden cardiac death. Although in
the first strip it remains unclear whether the cause of the AICD activation was atrial fibrillation or non-sustained VT, in the second strip
the device intervention successfully interrupted an episode of ventricular flutter accompanied with severe dizziness. (From: Gatzoulis K,
Gialafos J. Dual Chamber Antitachycardia Cardioverter Defibrillators. Another Step in the Treatment of High Risk Patients. Hellenic J
Cardiol 2003; 44: 71-9.)
(Hellenic Journal of Cardiology) HJC • 221
K.A. Gatzoulis et al
In general, patients presenting with severe LV dys- tients with IDCM, LV dysfunction and non-sustained
function, a history of syncope and recorded episodes VT, prophylactic AICD implantation showed a ten-
of non-sustained VT are considered to be at high risk dency to better long-term prognosis, although not
for sustained VT and SCD, although these risk fac- reaching the levels of statistical significance.87 Simi-
tors are less well defined in this case than in CHD.20 larly, a borderline trend for improved survival with
The role of PVS in IDCM remains unclear.78-81 an AICD among IDCM patients with LV dysfunction
Many authors believe that the induction of polymor- was well documented in the SCD-HeFT population.17
phic VT or VF represents a non-specific response.82-85 Additionally, a high incidence of appropriate shocks
However, it was recently shown that induction of poly- in AICD recipients with significant LV dysfunction
morphic VT/VF is related to more AICD interventions for both primary and secondary prevention was re-
over the long term than induction of sustained mono- cently documented.74,77,99-101
morphic VT or non-induction of VT.86 It is also be- It appears that the combination of complex ven-
lieved that, among asymptomatic patients, PVS does tricular ectopy with significant LV dysfunction de-
not have a place in risk stratification, although in some fines a high-risk group of symptomatic heart failure
studies the incidence of appropriate AICD shocks IDCM patients who may be protected by an AICD
during follow up in inducible patients was found to regardless of the results of PVS. Whether this is true
be higher than in non-inducible.73,84,85,87 The type of in asymptomatic heart failure IDCM patients, with
induced ventricular arrhythmia depends on the type better preserved LV function, remains unknown. In
of presenting clinical tachyarrhythmia.78,88-92 Indeed, summary, until ambiguous aspects are resolved in the
in cases of IDCM patients presenting with sustained light of newer data, it is recommended that all inva-
VT, the induction of sustained ventricular tachyar- sive and non-invasive diagnostic information should
rhythmias on PVS is extremely high, falling to 40% be collected and every case should be individualised
when the index arrhythmia is cardiac arrest and to before deciding what the proper therapy should be
25% when it is non-sustained VT.78,88-92 In summa- (Figure 2A & B).
ry, although induction of sustained VT during PVS is
generally associated with a poor prognosis, in IDCM
Arrhythmogenic right ventricular cardiomyopathy/
patients it is considered to be of minor value for pre-
dysplasia (ARVC/D)
dicting subsequent arrhythmic events.78-81,93 Contrary
to this so far prevailing view, there is old as well as re- A common limitation of the studies investigating
cent evidence that the induction of sustained VT/VF ARVC/D is the small number of patients included,
among either asymptomatic or syncopal patients is due to logistical difficulties in enrolling subjects with
the strongest predictor of future malignant ventricu- this unusual form of cardiomyopathy. Underpowered
lar arrhythmia events and thus might have a potential studies often prohibit investigators from drawing safe
role in the primary prevention of SCD in this popu- conclusions about the best approach for primary pre-
lation.92-94 Such information might be particularly vention of SCD in individuals with ARVC/D present-
important for the management of IDCM patients at ing with complex ventricular arrhythmias. In general,
earlier stages of heart failure, with better preserved young age, a family history of ARVC/D or SCD, syn-
LVEF, when presenting with complex ventricular ec- cope or aborted SCD, recorded episodes of VT, QRS
topy.91 Thus, prospective studies are necessary for dispersion ≥40 ms, T-wave inversion beyond V and
1
precise risk stratification. LV involvement are considered to be the major de-
On the other hand, magnetic resonance imaging terminants for adverse prognosis and impending sud-
showing areas of delayed gadolinium enhancement den death.102,103
might be helpful in identifying patients with IDCM Therapy with AICD implantation has been prov-
or other non-ischaemic cardiomyopathies at risk, but en to be life-saving in ARVC/D.104 Implantation for
this issue is still under investigation.95 secondary prevention is strongly recommended. Indi-
Although two of the early studies have failed cations for primary prevention are documented non-
to demonstrate any improvements in survival after sustained VT and/or syncope, in the presence of risk
AICD implantation in patients with IDCM, more re- factors such as extensive, progressively worsening RV
cent data revealed a protective effect in terms of SCD dysfunction, LV involvement, polymorphic VT, late
prevention and reduction of total mortality.17,87,96-98 potentials on SAECG, epsilon wave and a family his-
In a randomised multi-centre trial including 458 pa- tory.102,105,106 Moreover, in asymptomatic patients
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Ventricular Arrhythmias
A B
Figure 2. A: A 12-lead Electrocardiogram (ECG) and signal averaged electrocardiogram (SAECG) of a 72-year-old patient with idiopathic
dilated cardiomyopathy at an early stage (left ventricular ejection fraction 45%, New York Heart Association class I). Non-invasive assess-
ment revealed intermittent complete heart block, frequent episodes of non-sustained ventricular tachycardia and positive late potentials.
B: The subsequent EPS performed in the same patient documented the presence of high-degree atrioventricular block. Additionally, sus-
tained monomorphic ventricular tachycardia was easily induced. The patient remains alive 7.5 years later with the automatic implantable
cardioverter defibrillator (AICD) interrupting 6 episodes of sustained VT and ventricular flutter.
without a family history, if ARVC/D is severe PVS ty of gradual deterioration of both pacing and sensing
is recommended. If negative, conservative treatment thresholds of the defibrillator lead over time. Howev-
with β-blockers and follow up should be preferred. In er, it is possible that this type of treatment results in a
cases where sustained VT is triggered, the possibility better long-term prognosis in ARVC/D compared to
of prophylactic implantation of an AICD in combina- patients with CHD or IDCM and severe LV dysfunc-
tion with antiarrhythmic drugs should be considered. tion.
In asymptomatic patients with a family history, it is
controversial whether an EPS should be carried out,
Congenital heart disease
even in patients at low risk. On the other hand, in asym-
ptomatic patients without a family history and a mild Sudden cardiac death, of presumed arrhythmic aetiol-
form of ARVC/D, as well as in cases presenting with ogy, remains a leading cause of mortality in patients
sustained VT and palpitations but with a low risk pro- with congenital heart disease, showing an increased
file (e.g. none of the previously mentioned risk fac- incidence as the patient ages.119-121 Furthermore, the
tors), medical treatment and/or ablation is recom- number of adults with surgically corrected congenital
mended (Figure 3).102-118 heart disease has been increasing in the last years. Al-
Catheter VT ablation has been proposed in drug- though recent data demonstrate an increased risk of
refractory cases and, although effective in the short SCD in surgically corrected tetralogy of Fallot, great
term, has been associated with a high rate of recur- vessels transposition (Mustard or Senning operation),
rence.102,117 patients after the Fontan procedure, coarctation
In patients with ARVC/D the right ventricle is of the aorta, and aortic stenosis, it remains unclear
globally affected and thus AICD implantation is tech- how these patients should be approached when they
nically challenging. Additionally, there is a probabili- present with complex ventricular arrhythmias.122-126
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K.A. Gatzoulis et al
disease, suggest the use of AICDs in SCD survivors,
those with spontaneous sustained VT not success-
fully ablated, and those with inducible VT with unex-
plained syncope and impaired RV or LV function.133
Significant progress has been made in recent years
in the risk stratification process of patients with surgi-
cally corrected tetralogy of Fallot.124,134-139 High-risk
patients are those who had the operation at an older
age with several years of postoperative follow up, with
right ventricular dysfunction and dilatation, as well as
significant pulmonary valve regurgitation.124,134-139 The
12-lead ECG shows marked prolongation of the QRS
complex ≥180 ms, and an annual increase in QRS du-
ration with right bundle branch block.124,134-139 Other
recognised non-invasive risk factors are: increased car-
diothoracic ratios,139 at least moderate tricuspid valve
regurgitation and peripheral pulmonary stenosis,139 a
higher QT dispersion,139 impaired heart rate variabil-
ity,140 frequent ectopic beats,134 increased RV systolic
pressures,141 complete heart block,141,142 increased JT
dispersion,143 late gadolinium enhancement on MRI
scan,144 and LV dysfunction.145 In the early stages,
Figure 3. A 12-lead electrocardiogram (ECG) and signal averaged on the other hand, high-risk patients might be recog-
electrocardiogram (SAECG) in a 68-year-old patient with arrhyth-
nised by positive late potentials on the SAECG, in ad-
mogenic right ventricular cardiomyopathy/dysplasia (ARVC/D),
dition to mild RV dilatation and non-sustained VT
presenting with episodes of non-sustained ventricular tachycardia
(VT). The epsilon-wave can be clearly recognised in all 12 leads on the ambulatory ECG.146 A scoring system derived
of the ECG. Additionally, in the SAECG positive late potentials from surgical, haemodynamic, electrocardiographic
are identified when modified criteria are applied. The patient un-
and electrophysiological factors, categorising patients
derwent an electrophysiological study (EPS) resulting in sustained
as low, intermediate and high-risk has been report-
monomorphic VT induction. The patient remains alive 13 years
later with the automatic implantable cardioverter defibrillator ed.147 In patients with moderate risk, further stratifica-
(AICD) activated appropriately on one occasion. tion by means of PVS may be helpful.148-149 In patients
demonstrating a high risk, AICDs are increasingly uti-
lised in primary and secondary prevention; however,
Adults with unoperated aortic stenosis represent the further research is essential.147-150
highest-risk subgroup for SCD and ventricular ar- Finally, in patients who have undergone the Mus-
rhythmias in patients with congenital heart disease tard or Senning operation, atrial tachyarrhythmias151
that unfortunately persists despite surgical repair.125 and systemic RV dysfunction152 have also been iden-
It has been suggested that, similarly to other path- tified as important contributors to SCD. In a retro-
ological conditions affecting the left or right ventricle, spective study, risk markers included the presence
diagnostic techniques like ambulatory electrocardiog- of symptoms related to arrhythmia or cardiac failure
raphy, SAECG and EPS should be used in order to and a history of documented atrial fibrillation or flut-
determine the risk of SCD and subsequently adminis- ter, whereas the electrocardiogram, chest X-ray, and
ter an efficient antiarrhythmic treatment.127 In terms Holter findings were not predictive of SCD.153 The
of selection of the most effective methods for SCD role of AICDs in such patients remains unclear.153
prevention, radiofrequency catheter ablation of the
site of VT origin and AICD implantation have been
Patients without underlying heart disease
proposed (Figure 4).127-131 The former is a promis-
ing therapy but experience is still limited, whereas Complex ventricular arrhythmias, such as frequent
AICDs are considered to have a favourable impact ventricular ectopic beats, ventricular couplets and
on long-term outcome.132 The latest guidelines for non-sustained VT, are considered to be of favourable
the management of patients with congenital heart prognosis in patients without structural heart disease,
224 • HJC (Hellenic Journal of Cardiology)
Ventricular Arrhythmias
A B
Figure 4. A 12-lead electrocardiogram (ECG) and electrophysiological study (EPS) performed in a 38-year-old patient with a surgically
repaired atrial septal defect 12 years ago. For the last 4 years the patient presented with multiple episodes of paroxysmal atrial flutter and
wide-complex tachycardia (WCT). Figure 4A shows WCT reproduced during EPS. Atrioventricular dissociation can be observed, indicat-
ing the presence of sustained ventricular tachycardia (VT). In figure 4B entrainment of sustained VT can be observed during pacing from
the successful ablation VT site in the right ventricle. Presystolic electrograms were also recorded at this site.
provided that conditions like Brugada syndrome, long- Finally, patients with multiple risk factors for
QT syndrome, idiopathic ventricular tachycardia, or CHD who present with non-sustained VT should be
subclinical forms of ARVC/D are excluded.154-161 The further investigated to exclude CHD, even when exer-
diagnosis of Brugada and long-QT syndromes is estab- cise testing is normal.
lished from the characteristic ECG changes in addition In general, patients without apparent heart dis-
to the clinical presentation and a positive family his- ease who present with complex ventricular arrhyth-
tory.20 On the other hand, further investigation for id- mias should be thoroughly examined. In a retrospec-
iopathic ventricular tachycardia and ARVC/D should tive study of 270 patients who presented with sudden
take place in patients presenting with ventricular ar- cardiac arrest in the “absence” of heart disease, care-
rhythmias originating from the RV. ful examination revealed structural disease in 95% of
In a series of 37 patients without underlying struc- them.165
tural heart disease, who presented in our department
with a complex ventricular arrhythmia that was origi-
Congestive heart failure (CHF)
nally classified as “idiopathic ventricular arrhythmia
from the right ventricle”, changes in the 12-lead ECG The detection of complex ventricular arrhythmias in
and the SAECG, as well as minor abnormal findings patients with CHF of any aetiology is not rare, and is
in echocardiography—especially in the RV—were in- related to an increased cardiac mortality and a high
deed not infrequently recorded.162 Furthermore, sus- incidence of SCD.
tained ventricular tachyarrhythmia was occasionally In addition, AICD implantation in these patients
triggered on PVS. The prognostic value of these find- was recently proven efficacious, resulting in reduced
ings, as well as the possibility that they could be re- incidence of SCD and prolonged life expectancy. Re-
lated to subclinical forms of RV cardiomyopathy, are sults from the MADIT II trial revealed that implant-
currently under investigation. able defibrillators should be considered in all post-MI
Another group of patients that requires further patients with severe ventricular dysfunction.16 In ad-
investigation when presenting with non-sustained VT dition, SCD-HeFT, a study recruiting patients with
without detection of underlying structural heart dis- NYHA class II/III and LVEF<35% to receive pla-
ease, are the elderly. It is possible that, besides the cebo, amiodarone, or an AICD, demonstrated an ab-
well known conduction abnormalities often recog- solute mortality reduction of 7.2% after five years in
nised in these patients, degeneration of the Purkinje patients who received an AICD.17 This evidence led
fibres leading to organised re-entry circuits may also the US Centre for Medicare & Medicaid Services to
develop (Figure 5).163,164 conclude that an AICD is “reasonable and necessary”
(Hellenic Journal of Cardiology) HJC • 225
K.A. Gatzoulis et al
Figure 5. A 12-lead electrocardio-
gram (ECG) and electrophysiologi-
cal study (EPS) in an 83-year-old
patient without underlying heart
disease, presenting with palpita-
tions, non-sustained ventricular
tachycardia (VT), sinus bradycar-
dia, 1st degree atrioventricular
block and left bundle branch block.
On programmed ventricular stimu-
lation (PVS), haemodynamically
unstable sustained VT was easily in-
duced (2 ventricular extrastimuli),
despite the absence of myocardial
ischaemia or left ventricular dys-
function. The patient died suddenly
while asleep 4 years later, after the
implantation of a DDDR pacemak-
er, despite the concurrent adminis-
tration of amiodarone.
for “patients with ischemic cardiomyopathy, prior MI, priate AICD activation in biventricular AICD re-
NYHA Class II/III, and measured LVEF<35%.”26 cipients.166 This implies that better risk stratification
Furthermore, according to the current guidelines, in tools, beyond the degree of LV dysfunction, are need-
patients with CHD, LVEF≤35%, NYHA Class II/ ed if the number of patients likely to benefit from an
III and LVEF≤30%, or NYHA Class I, 40 days post- AICD is to be maximised.26
MI, are all indications for AICD implantation (Class The same approach should also be used for can-
IA), whereas in patients with LVEF≤40% plus the didates for biventricular pacing in an advanced stage
presence of non-sustained VT on Holter monitoring of CHF, with intraventricular conduction abnormali-
and inducible VT on PVS, the indication for AICD ties, and in patients who show a delay in LV contrac-
insertion is classified as IB. In cases of LVEF in the tion, even at earlier stages of heart failure (Figure
range 30-35% and NYHA class I, the indication is not 6).167-172 Indeed, patients with CHF treated with bi-
specified. On the other hand, in IDCM patients with ventricular pacing plus an AICD not only demon-
LVEF<35%, in NYHA class II/III and LVEF<35% strated a significant clinical improvement, but also
in NYHA class I, the indications for AICD implanta- showed the longest life expectancy.170
tion are I (level of evidence B) and IIb (level of evi-
dence C), respectively.74
Benign ventricular arrhythmias
The appropriate AICD activation rate during the
long-term follow up is higher when the risk stratifica- The long-term prognosis of patients presenting on-
tion process is EP guided and clearly ventricular ar- ly with single ventricular ectopic beats, without com-
rhythmia oriented. We previously demonstrated that plex forms of ventricular arrhythmia recorded on
induction of sustained VT on EPS predicted appro- the ambulatory ECG, and when underlying structur-
226 • HJC (Hellenic Journal of Cardiology)