Dr. Frank L.Y. Tam Queen Elizabeth Hospital Cardiology Division

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.

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 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

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 life- threatening 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.