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Fatal cardiac arrhythmias in patients with heart failure: Risk stratification, treatment and prevention Dr.. In MUSTT trial, patients with abnormal SAECG has higher rate of arrhythmi

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

• Risk stratification for SCD

• Role of ICDs for 1ry and 2ry prevention

• Catheter ablation and drug treatment

• Other considerations

Outline of presentation

Incidence of Sudden Cardiac Death

• 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

SCD in post MI patients

Events leading to SCD in post MI patients

Liew R; Heart 2010

Outline of presentation

• Risk stratification for SCD

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

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)

Images from UCLA arrhythmia centre

Correlation of myocardial scar on MRI with voltage map

Outline of presentation

• Role of ICDs for 1ry and 2ry prevention

Implantable cardioverter defibrillators

• Useful to protect against

sudden arrhythmic death, but

have their own associated

– 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

• 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

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 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

Outline of presentation

• Catheter ablation and drug treatment

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 life- threatening 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 ischaemic systolic heart failure-

non-Kober 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

• Other considerations

MOLECULAR AUTOPSY IN SCD VICTIMS

European Society of Cardiology 2015

Genes most commonly altered in cardiomyopathies

THE SUBCUTANEOUS ICD

Bardy et al NEJM 2010

SUBCUTANEOUS ICDs

• 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)

T +65 6694 0050

Which parameters will help identifying

patients

who require ICD?

• NYHA functional class and presence of sustained VT do not provide incremental value

non-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?

• 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

• 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

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