Download Fatal cardiac arrhythmias in patients with heart failure: Risk

Fatal cardiac arrhythmias in
patients with heart failure:
Risk stratification, treatment and
prevention
Dr. Reginald Liew
MA, MB BS (Hons), PhD, FRCP, FACC, FESC, FAsCC
Director/ Senior Consultant Cardiologist
The Harley Street Heart and Cancer Centre
Mount Elizabeth Novena Specialist Centre, Singapore
Outline of presentation
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Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
Outline of presentation
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•
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Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
Incidence of Sudden Cardiac Death
SCD in post MI patients
• 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.
Events leading to SCD in post MI patients
Liew R; Heart 2010
Outline of presentation
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Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
Which parameters will help identifying
patients who require ICD?
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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
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
Liew R; Heart 2010
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)
Correlation of myocardial scar on
MRI with voltage map
Images from UCLA arrhythmia centre
Outline of presentation
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Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
Implantable cardioverter defibrillators
• Useful to protect against
sudden arrhythmic death, but
have their own associated
risks
– Inappropriate shocks
– Need for regular generator
change
– Risk of infection
– May cause vicious cycle of
further arrhythmias due to
adrenergic drive
• Risk/ benefit ratio needs to
be discussed fully with pt and
parents
• General principles:
– Indicated in pts after aborted SCD (2rd prevention)
– Consider for 1ry prevention in patients at high risk of SCD
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 nonarrhythmic/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, reentrant arrhythmia is the primary mechanism for
mortality when ICD can significantly impact survival.
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)
PRIMARY PREVENTION OF SCD WITH THE ICD
European Society of Cardiology
SUMMARY- SCD and ICDs in heart failure pts
• At present, 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 reevaulate 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.
Outline of presentation
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•
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Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
MANAGEMENT OF SUSTAINED VT IN PATIENTS
WITH IHD
DRUGS FOR THE TREATMENT OF
VENTRICULAR ARRHYTHMIAS AND SCD
• Other than beta-blockers, no other AADs
have been shown in RCT to be effective in
primary management of patients with lifethreatening ventricular arrhythmias and
reducing the risk of SCD
• Each drug can potentially cause adverse
events, including pro-arrhythmia
AMIODARONE IS NO BETTER THAN PLACEBO
AT PREVENTING SCD
Bardy et al. NEJM 2005
CATHETER ABLATION OF VT
Catheter ablation of VT
VT ablation versus escalation of anti-arrhythmic
drugs- Sapp et al. NEJM July 2016
• Multicentre RCT in 259 pts with ischaemic
cardiomyopathy, ICD and recurrent VT
despite being on AADs
• Randomised to VT ablation (132 pts) or
escalation of AAD (amiodarone or mexiletine if
already on 300mg amiodarone per day; 127
pts)
• Primary end-point composite of death, VT
storm, or appropriate ICD shock
Sapp JL et al. N Engl J Med 2016;375:111-121
Defibrillator implantation in patients with nonischaemic systolic heart failureKober et al NEJM Aug 2016
• RCT of 556 patients with symptomatic
systolic heart failure (LVEF ≤35%) not caused
by coronary artery disease were assigned to
receive an ICD, and 560 patients were
assigned to receive usual clinical care (control
group).
• In both groups, 58% of the patients received
CRT.
• The primary outcome was death from any
cause. The secondary outcomes were sudden
cardiac death and cardiovascular death
• No sig. difference in 1ry
outcome (death from any
cause) between ICD and
control group.
• Sig. reduction of SCD in
ICD group (2ry outcome)
Outline of presentation
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•
•
•
•
Incidence and epidemiology
Risk stratification for SCD
Role of ICDs for 1ry and 2ry prevention
Catheter ablation and drug treatment
Other considerations
MOLECULAR AUTOPSY IN SCD VICTIMS
European Society of Cardiology 2015
Genes most commonly altered in cardiomyopathies
Gene name
Gene symbol
Frequency (%)
Hypertrophic cardiomyopathy
Beta-myosin heavy chain
MYH7
15–25
Cardiac myosin-binding
protein C
MYBPC3
15–25
Cardiac troponin T
TNNT2
<5
Cardiac troponin I
TNNI3
<5
Alpha-tropomyosin
TPM1
<5
LIM-binding domain 3
LBD3
1–5
Ventricular regulatory myosin
light chain
MYL2
<2
Myosin light chain 3
MYL3
<1
Cardiac muscle alpha actin
ACTC1
<1
Long QT syndrome
Potassium channel, voltage
KCNQ1
gated, member 1 (Kv7.1; LQT1)
40–55
Potassium channel, voltage
gated, member 2 (Kv11.1;
LQT2)
KCNH2
30–45
Sodium channel, voltage
gated, type V, α subunit
(Nav1.5; LQT3)
SCN5A
5–10
Arrhythmogenic right ventricular cardiomyopathy
Plakophilin 2
PKP2
10–45
Desmoplakin
DSP
10–15
Desmoglein
DSG2
7–10
Desmocollin 2
DSC-2
2
Junction plakoglobin
JUP
<1
THE SUBCUTANEOUS ICD
Bardy et al. NEJM 2010
SUBCUTANEOUS ICDs
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Effective at preventing SCD
Avoids complications related to traditional transvenous systems
Long term data lacking
Not useful if pacing is required (including CRT) or if ATP is required for
VT termination
WEARABLE CARDIOVERTER DEFIBRILLATOR
• No prospective randomized trials evaluating the device
have yet been reported
• Small case series, registries and case reports have
reported successful use of the WCD in a small proportion of
patients
WEARABLE CARDIOVERTER DEFIBRILLATOR
A recording from a LifeVest of an appropriate shock delivered to a patient with long-QT
syndrome. The wearable defibrillator was prescribed after ICD extraction as a result of infection.
All plates show the 2 channels used by the wearable defibrillator.
WEARABLE CARDIOVERTER DEFIBRILLATOR
Conclusions
• Various methods for risk stratification of fatal
arrhythmias in pts with heart failure - LVEF remains
most widely used and featured in guidelines
• ICDs can lower risk of SCD- timing is important
• Medical therapy not effective to reduce SCD but can
be useful to reduce ICD shocks
• Catheter ablation of VT/ VF indicated for recurrent
ventricular arrhythmias or ICD shocks; should be
done in experienced EP centres
• Newer options to consider- subcutaneous ICD,
wearable cardioverter defibrillator (short term
measure)
Gleneagles Hospital,
#02-38/41, Annexe Block
6A Napier Road, Singapore
T +65 6472 3703
Email: [email protected]
www.harleystreet.sg
Mount Elizabeth Novena Specialist Centre
#07-41, 38 Irrawaddy Road,
Singapore
T +65 6694 0050
Which parameters will help identifying
patients
who require ICD?
• NYHA functional class and presence of nonsustained 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.
DIAGNOSTIC WORKUP FOR PATIENTS
PRESENTING WITH SUSTAINED VT/ VF
DIAGNOSTIC WORKUP FOR PATIENTS
PRESENTING WITH SUSTAINED VT/ VF
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.
Microvolt T Wave Alternans?
• Measures 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
• 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%.
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)
Causes of SCD among children and young
adults- Bagnall et al, NEJM 2016
• CAD still most common cause
• Among cases of unexplained SCD, genetic testing with autopsy
helped identify cause