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Transcript
Dr. Frank L.Y. Tam
Queen Elizabeth Hospital Cardiology Division
Incidence of Sudden Cardiac Death
Events
Incidence
General
population
High-risk
subgroups
Any prior
coronary event
EF<30% or
heart failure
MADIT II
Cardiac arrest
survivor
AVID, CIDS, CASH
Arrhythmia risk
markers, post MI
SCD-HeFT
MADIT I, MUSTT
0
10
20
Percent
30
0
150,0000
300,000
Absolute Number
 Atherosclerotic coronary artery disease remain the
most important underlying substrate for accountable
sudden cardiac death.
 Survivors of myocardial infarction especially with left
ventricular dysfunction, is the high risk population
being focused on and where most of the data has been
available.
Risk of SCD post MI is highest in the first month
 Data from the VALIANT trial
showed the SCD risk is highest in
the first 30 days post MI
 With each 5% decrease in LVEF,
there was 21% increase in relative
risk of SCD during this period
 SCD risk decrease with time and
plateau at 12 months equalized
between different LVEF categories.
 This temporal trend is also noted
in combined analysis of other
trials (EMIAT, CAMIAT, SWORD,
TRACE, DIAMOND-MI)
Which parameters will help identifying patients
who require ICD?
 NYHA functional class
 Non-sustained VT
 QT dispersion and variability
 Cardiac autonomic modulation (HRV, BRS, HRT)
 Signal –averaged ECG
 Microvolt T wave alternans
 EP testing
 LVEF
Which parameters will help identifying patients
who require ICD?
 NYHA functional class and presence of non-sustained
VT do not provide incremental value in risk
assessment over other parameters such as LVEF.
 In MADIT II and some small epidemiological studies,
QT measurements had been shown to be associated
with malignant ventricular arrhythmias. However the
sensitivitiy was too low to be clinically useful.
Which parameters will help identifying patients
who require ICD?
 Patients with depressed baroreflex sensitivity(BRS)
<3ms/mmHg and depressed heart rate variability(HRV)
SDNN<70ms had been shown to have higher total
mortality (17% vs 2% with both tests normal). But
neither of these tests had been shown useful in
predicting arrhythmic death
 Heart rate turbulence (HRT) show mixed results in
trials. It predicts total mortality in EMIAT, MADIT II
and Multicenter Post Infarct Program trials but there
is limited data for its SCD prediction.
Which parameters will help identifying patients
who require ICD: Signal averaged ECG?
 Late potential represents low amplitude
high frequency electrical activity at the
terminal portion of QRS. Thought to be
due to slow conduction and delayed
myocardial activation, a marker of
ischemic substrate.
 The prognostic value of SAECG had been
reported. In MUSTT trial, patients with
abnormal SAECG has higher rate of
arrhythmic and total mortality (36% vs
13% 5 yr incidence) but the sensitiviy and
specificity was inadequate to guide ICD
therapy
Which parameters will help identifying patients
who require ICD: Microvolt T Wave Alternans?
 Microvolt electrical alternans is the variability of ECG
waveform on alternate beats, as pathophysiological
manifestation in serious heart disease or in normal subjects
when heart rate is very rapid.
 The T wave is measured at identical time relative to QRS in
multiple consecutive complexes. Spectral analysis is used to
differentiate minor alternation in T wave morphology at
the alternans frequency from respiration and noise.
 T-Wave Alternan (TWA) is measured during atrial pacing
or exercise for a target heart rate of 110bpm to maxmize
sensitivity and specificity.
Which parameters will help identifying patients
who require ICD: Microvolt T Wave Alternans?
 Gehi et al. reported in a meta-analysis of cohort studies between
1990-2004 a harzard ratio of 3.8 with abnormal MTWA and NPV
of 92% in ICM, 95% in NICM, and 99% in post MI patients.
 However high discordance rate between 1 and 6 month post MI
was reported by Oliveira et al.
 2 major trials in 2008 with ICD population
 MASTER (Chow et al. JACC 2008) (n=575 ICM EF</=30%)
 MTWA SCD-HeFT (Gold et al. Circ 2008) (n=490 ICM and NICM
EF </=35%)
 Both failed to show a difference in primary endpoint (SCD and ICD
discharge) between test negative and non-negative (positive and
indetermine) patients
MTWA: failure to demonstrate a difference in primary endpoint
 MTWA still lacks the reproducibility and predictive accuracy as sole
parameters to predict SCD and need for ICD for post MI patients
Which parameters will help identifying patients
who require ICD:EP testing?
 In the past, EP testing was considered the primary method
for risk stratification for malignant ventricular arrhythmia.
 The value of EP testing is challenged in MUSTT-EPS
registry (n=1397) and MADIT II EP substudy (n=593).
 Although EP testing does stratify CAD patients at risk of
SCD, its ability to do so is only modest.
 MUSTT-EPS: non-inducible = 12% arrhythmic death at 2 yr.
(NPV 88% at 2 year)
 MADIT II EP: non-inducible = 25.5% ICD Rx at 2 yr. (vs 29.4%
for inducible patients NS)
 The major finding of MUSTT-EPS registry is that 2 year
and 5 year rate of cardiac arrest or death by arrhythmia in
the non-inducible cohort were still 12% and 24%.
Imaging the substrate
 Ischemia and scarring from CAD result in abnormal
myocardial substrate and predispose to life-threatening
arrhythmia
 Traditional tools in assessing LVEF include 2D
echocardiogram and radionuclide imaging
 Cardiac MR has emerged as a promising tool in risk
assessment arena, providing accurate measurements in
LVEF and dimensions, perfusion abnormality, infarct size
and viability assessment (DGE). DGE identified regional
fibrosis in NICM and ICM and correlates with appropriate
ICD Rx (Iles et al. JACC 2011)
Clinical trials of ICD therapy
using LVEF as primary risk assessment tool
Benefit of ICD for SCD is offset in early post MI
Impact of ICD therapy is Time dependent
Impact of ICD therapy is Time dependent
 The benefit of ICD early vs late post MI does not seem to be
similar.
 Potent reduction in total mortality by ICD has been confirmed
when implemented in a ICM population with remote MI.
 Although SCD risk is highest early post MI, ICD does not impact
total mortality. ICD merely changes the mode of death from
arrhythmic death to non-arrhythmic/heart failure death.
 It seems that remodelling of ventricle early post MI negates the
ICD benefits, yet in late post MI when the substrate becomes
stable with healed scar tissue, re-entrant arrhythmia is the
primary mechanism for mortality when ICD can significantly
impact survival.
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
 Exercise testing is recommended in adult patients
with ventricular arrhythmias who have an
intermediate or greater probability of having CHD by
age, gender, and symptoms to provoke ischemic
changes or ventricular arrhythmias.
(Class I level B)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
 Ambulatory ECG is indicated when there is a need to clarify the
diagnosis by detecting arrhythmias, QT-interval changes, T-wave
alternans (TWA), or ST changes to evaluate risk, or to judge
therapy. (Class I level A)
 Event monitors are indicated when symptoms sporadic to
establish whether or not they are caused by transient
arrhythmias. (Class I level B)
 Implantable recorders are useful in patients sporadic
symptoms suspected to be related to arrhythmias such as
syncope when a symptom-rhythm correlation cannot be
established by conventional diagnostic techniques. (Class I level
B)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac death
 It is reasonable to use T-wave alternans to improve the
diagnosis and risk stratification of patients with ventricular
arrhythmias or who are at risk for developing lifethreatening ventricular arrhythmias. (Class IIa level A)
 ECG techniques such as signal-averaged ECG(SAECG),
heart rate variability (HRV), baroreceptor reflex
sensitivity, and heart rate turbulence may be useful to
improve the diagnosis and risk stratification of patients
with ventricular arrhythmias or who are at risk of
developing life-threatening ventricular arrhythmias.
(Class IIb level B)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac death
Echocardiography is recommended in patients
 with ventricular arrhythmias who are suspected of
having structural heart disease. (Class I level B)
 at high risk for the development of serious
ventricular arrhythmias or SCD, such as those with
dilated, hypertrophic, or RV cardiomyopathies,
AMI survivors, or relatives of patients with
inherited disorders associated with SCD. (Class I
level B)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac death
 Exercise testing with an imaging modality
(echocardiography or nuclear perfusion (SPECT) is
recommended to detect silent ischemia in patients with
ventricular arrhythmias who have an intermediate probability of
having CHD by age, symptoms, and gender and in whom ECG
assessment is less reliable because of digoxin use, LVH, >1-mm
ST depression at rest, WPW syndrome, or LBBB. (Class I level B)
 Pharmacological stress testing with an imaging modality
(echocardiography or myocardial perfusion SPECT) is
recommended to detect silent ischemia in patients with
ventricular arrhythmias who have an intermediate probability of
having CHD by age, symptoms, and gender and are physically
unable to perform a symptom-limited exercise test. (Class I level
B)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac death
 MRI, cardiac computed tomography (CT), or
radionuclide angiography can be useful in patients
with ventricular arrhythmias when echocardiography
does not provide accurate assessment of left
ventricular (LV) and RV function and/or evaluation of
structural changes. (Class IIa level B)
 Coronary angiography can be useful in establishing
or excluding the presence of significant obstructive
CHD in patients with life-threatening ventricular
arrhythmias or in survivors of SCD, who have an
intermediate or greater probability of having CHD by
age, symptoms, and gender. (Class IIa level C)
ACC/AHA/ESC 2006 Guidelines
Ventricular Arrhythmias and the Prevention of Sudden Cardiac death
 EP testing is recommended in patients with
syncope of unknown cause with impaired LV
function or structural heart disease.(Class I level B)
 EP testing can be useful in patients with syncope
when bradyarrhythmias or tachyarrhythmias are
suspected and in whom noninvasive diagnostic
studies are not conclusive.(Class IIa level B)
ACCF/AHA/HRS 2012 focused updated Guidelines
Device –based Therapy for Cardiac Rhythm Abnormalities
ICD therapy is indicated in patients:
 who are survivors of cardiac arrest due to ventricular
fibrillation or hemodynamically unstable sustained VT
after evaluation to define the cause of the event and to
exclude any completely reversible causes. (Class I level A)
 with structural heart disease and spontaneous sustained
VT, whether hemodynamically stable or unstable. (Class I
level B)
 with syncope of undetermined origin with clinically
relevant, hemodynamically significant sustained VT or VF
induced at electrophysiological study. (Class I level B)
ACCF/AHA/HRS 2012 focused updated Guidelines
Device –based Therapy for Cardiac Rhythm Abnormalities
ICD therapy is indicated in patients with:
 LVEF less than or equal to 35% due to prior MI who
are at least 40 days post-MI and are in NYHA
functional Class II or III. (Class I level A)
 LV dysfunction due to prior MI who are at least 40
days post-MI, have an LVEF less than or equal to 30%,
and are in NYHA functional Class I. (Class I level A)
 nonsustained VT due to prior MI, LVEF less than or
equal to 40%, and inducible VF or sustained VT at
electrophysiological study. (Class I level B)
Conclusion
 Up to date, other than LVEF measured at least 40 days post
MI, there is no non-invasive or invasive strategy that can
reliably predict SCD risk and guide ICD therapy, especially
soon after MI.
 For early post MI patients, the management directive is to
maximize optimal medical therapy and revascularization
(early if not primary), and re-evaulate LVEF at 40 days post
MI or revascularization for indication of ICD .
 For stable ischemic cardiomyopathy patient, LVEF still
provide the most validated and powerful risk assessment to
guide the need for prophylactic ICD.