Dr Arindam Pande, MBBS (Hons), MD, DM (Cardiology)
Consultant Cardiologist,Academic Coordinator: DNB Cardiology and PGDCC Training
Apollo Gleneagles Hospital, Kolkata
“Primary Prevention Of Sudden Cardiac Death - Role Of Devices”
Lets start with an case example…
• 64 year genleman• Heavy smoker, T2DM, HTN• Chest pain of 11 hours• ECG – acute ASMI• ECHO at ER reveals EF – 27%• Ongoing chest pain• Planned for Primary PCI
Follow up at 1.5 months
• No chest pain/angina• Mild SOBE, NYHA Class 2• Resumed normal activity• BP – 120/70 mmHg, • HbA1C – 6.2%• Lipid profile and other biochemical parameters
– within normal limits• ECHO: LVEF - 34%
Definition SCD is natural death from cardiac causes
heralded by abrupt loss of consciousness within 1 hour (Rapid- interval between the onset of symptoms to cardiac arrest) of the onset of an acute change in cardiovascular status
Preexisting heart disease may or may not have been known to be present, but the time and mode of death are unexpected
# -Sudden Cardiac arrest - abrupt cessation of cardiac mechanical function, which may be reversible with prompt intervention but will lead to death in its absence
# -Sudden cardiac death -Sudden, irreversible cessation of all biologic function
< 35 years
Prevention of cardiac arrest and SCD Primary prevention
High risk patients of advanced heart disease with low EF and other high risk markers
Less advanced common or uncommon structural heart diseases
Structurally normal hearts, subtle or minor structural abnormalities, or genetically based molecular disorders that establish risk for ventricular arrhythmias
General population
Secondary preventionPrevention of recurrent events in survivors of cardiac
arrest or pulseless VT or other symptomatic tachycardias considered life-threatening
Strategies ICD Antiarrhythmic drugs Catheter ablation Antiarrhythmic surgery The choice of a therapy is based on
Estimation of risk of the individual patientAvailable efficacy and Safety data
30 days survival rates ranged from a maximum of 48% with responses shorter than 2 minutes to less than 5% with response time longer than 15 minutes
Electrical mechanisms of cardiac arrest Tachyarrhythmia
Ventricular fibrillation and Pulseless sustained VT
BradyarrhythmiasSevere bradyarrhythmias (< 20
beats /min)Pulseless electrical activity
In Summary SCD is not common About half of all cardiovascular deaths Approx. 50% of all SCDs are unexpected
first expressions of a cardiac disorder High-risk people usually identified by
symptoms or family history – priority for evaluation
Cure not possible, but correct management can prevent complications
ICDs The first generation of defibrillators required a
thoracotomy to place the sensing and defibrillator leads epicardially, and the generator size mandated implantation of the device in an abdominal pocket
Current-generation ICD integrate pacing, sensing, and high-voltage defibrillation abilities have the additional ability to deliver low-energy
cardioversion, ATP for VT, and anti bradycardia pacing Given the excellent safety and good profile of
current ICD, implantation is not a major challenge Identification of patient populations most appropriate for
this potentially lifesaving therapy
Randomised Trials of ICD Therapy“Primary prevention” - patients who
have not yet had VT or VF, but are thought to be at high risk
Multicenter Automatic Defibrillator Implantation Trial (MADIT 1) -1996
Multicenter UnSustained Tachycardia Trial (MUSTT) - 1999
MADIT 2 – 2002 COMPANION – 2004 SCD-HeFT - 2004
5 10 20 30 40
CATCAT
CABG-PatchCABG-Patch
MUSTTMUSTT
MADIT IMADIT I
ns VT ns VT
High riskHigh riskno VAno VA MADIT IIMADIT II
DINAMITDINAMIT
SCD-HeFTSCD-HeFT
DEFINITEDEFINITE
LV-EF (%)LV-EF (%)
ICD Trials - Primary prophylaxis
ICD 10 Prevention Trial Results
CABG-Patch
MUSTT
MADIT I
MADIT II
DINAMIT
SCD-HeFT
DEFINITE
AMIOVIRT
CAT
0 0.5 1 1.5 2 2.5
CAD, MI
NICM
CAD, NICM
Hazard Ratio
ICD better No ICD better
Overview of Primary Prevention Trials Results
MADIT 54% reduction in mortality with ICD
MUSTT 55-60% reduction in mortality with ICD MADIT II 31% reduction in mortality with ICD
DEFINITE Mortality benefit 5.7% at 2 years with ICD SCDHeFT 23% reduction in mortality with ICD
Risk stratification for sudden death in ICD trials
Ejection fraction(EF <30%, <35%, <40% + ...)
Etiology of depressed EF(CAD vs DCM)
EP study(inducible VT, VF)
Timing of remote myocardial infarction(< 40 days, > 40 days / 1 month)
[HRV] NYHA class QRS duration
LV-EF is considered as the best parameter for risk stratification after MIexponential increase of risk of SCD below EF 35-40%
LV-EF (%)
risk
LV-function as predictor of SCD
MUSST, MADIT, MADIT-2, SCD-HeFTDINAMIT, COMPANION, ………
MADIT Trial 1st RCT comparing AADs (Amiodarone)
& ICD This trial included post MI > 1 month
EF < 35%NSVT during ambulatory recording and
inducible VT that was not suppressible by IV procainamide
This very high-risk group demonstrated a 54% reduction in total mortality with ICD therapy versus drug therapy
Moss et al N Engl J Med 1996; 335: 2933-40
MADIT - Results
Moss et al N Engl J Med 1996; 335: 2933-40
Multicenter unsustained tachycardia trial (MUSTT) Assess to identify NSVT In post MI with
other risk markers for early mortalityEF < 40%. Inducible VTAmbient NSVT
The results demonstrated a statistically significant beneficial effect on total mortality (subgroup who not responded)
MUSTT - Results
Buxton et al. N Engl J Med 1999 ;341:1882-90
ICD Trials: Why is the benefit greater in “Primary Prevention” studies? In AVID, CASH and CIDS, the main entry
criterion was ventricular arrhythmiaSome patients had preserved LV functionMortality reduction with ICD 28% overallMortality reduction 34% in patients with LVEF <
35% In MADIT and MUSTT, the main entry
criterion was poor LV functionLVEF <35% in MADIT, <40% in MUSTTMortality reduction with ICD 54 - 60%Heterogeneity in antiarrhythmic drug use
Who benefits most from ICDs?
1990’s Patients at highest risk
of sudden death are those with ventricular arrhythmias (spontaneous or induced)
The ICD is a treatment for ventricular arrhythmias
2000’s Patients at highest risk
of sudden death are those with heart failure due to poor LV systolic function
The ICD is a treatment for heart failure
MADIT II trial Survival benefit of ICDs in patients of post MI with
rEF -30% NYHA II & III No arrhythmic markers for inclusion A total 1232 patients in a 3 : 2 ratio ICD (742) or
conventional medical therapy (490). Av EF- 23% An Av follow-up of 20 months All-cause mortality rates were 19.8% in the conventional
arm and 14.2% in the ICD group (31% RRR, P = 0.016) The findings suggested that HF patients with mild to
moderate symptoms and moderate to severe reductions in LVEF may benefit the most from a prophylactic ICD as early as 9 months
MADIT II Results
Moss et al New Engl J Med 2002; 346: 877-883
MADIT- IISubgroup analyses and additional
tests Heart rate variability (several
parameters), signal averaged ECG - not useful
EP study performed in those with ICDIf EP +ve, more likely to get VTIf EP -ve, more likely to get VF !Overall limited usefulness
QRS width - powerful predictor of benefit from ICD
Moss et al New Engl J Med 2002; 346: 877-883
MADIT II - Subgroup analysis
Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) It was designed to evaluate any possible
benefit of ICD early after MITotal 674 patients with Recent (6-40 days) MI EF < 35%, depressed HRV Mean 24-hour HR > 80/minTested ICD/ no ICD
ICDs do not appear to be of benefit immediately after large MI (unexplained increase in non arrhythmic death)
Defibrillator implantation in nonischemic CMP (DEFINITE) trial 1st RCT of primary prevention therapy with
an ICD in patients with non ischemic CMPEF of 35% or less, a history of symptomatic HFAmbient arrhythmia defined as an episode of
NSVT or at least 10 PVCs per 24-hour period during continuous ambulatory ECG
229 patients to each arm of the study ICD + standard medical therapy/standard
medical therapy alone
DEFINITE trial Follow -29.0+\-14.4 months with primary endpoint all-cause
mortality Total 68 deaths were reported
28 in the ICD group and 40 in the standard therapy group
ICD yielded Non-significant 35% reduction in death from any cause (P = 0.08) Significantly reduced the risk for SCD by a remarkable 80% (P =
0.006) In the subgroup of NYHA class III patients, all-cause mortality was
significantly decreased in the ICD arm (P = 0.02) The results demonstrated a strong trend toward a survival
advantage for patients receiving an ICD
Sudden Cardiac Death–Heart Failure Trial This landmark RCT addressed two
important issues (1) Whether empiric Amiodarone therapy saves lives in well-treated patients with NYHA class II and III (2) Whether a prophylactic ICD saves lives
Total 2521 patientsNYHA class II (70%) or III (30%) LVrEF (≤35%; mean, ≈25%) Ischemic or nonischemic SCD-HeFT trial had 3 arm ICD/Amiodarone/ placebo
Sudden Cardiac Death–Heart Failure Trial The median follow-up was 45.5 months An ICD was associated with a
statistically significant 23% reduction in all-cause mortality in comparison to placebo ( P = 0.007)
Mortality in the amiodarone arm was not significantly different from that in the placebo arm across all subgroups
SCD and ICD Summary SCD – THE leading cause of death in the US and whole worldICDs superior to optimal medical mgmt alone as demonstrated in multiple clinical trials Patients at risk need to be identified before they have SCD
KNOW YOUR PATIENT’S EF !!!! ICDs are cost-effective and underutilized ICD therapy can be painless The mortality risk of NOT having an ICD far outweighs the risk of device failure
Guidelines
Current ACC/AHA/HRS guidelines for ICD
ICD
Class I VT/VF survivors with irreversible etiology sustained VT with structural heart disease syncope + VT/VF at EPS NYHA II-III, LV EF<35% NYHA I, post-MI, LV EF<30% NSVT, post-MI, LV EF<40%, VT/VF at EPS
ICD Class IIa syncope, LV dysfunction, non-ischemic DCM Sustained VT HCM with major risk factors ARVD with major risk factors LQTS with syncope while on BB therapy transplant bridge Brugada syndrome with syncope or VT Catecholaminergic polymorphic VT with syncope
ICD Class IIb
NYHA I, LV EF<35% LQTS and SCD risk factors idiopathic syncope and advanced SHD familial CMP LV noncompaction
ICDClass III
Expected survival less than 1 year (other cause)
Incessant VT/VF Significant psychiatric illness NYHA IV without transplant or CRT indication Idiopathic syncope with no inducible VT/VF
and SHD VT/VF amenable with ablation VT/VF with reversible cause
Take home message.. ICD is most cost‑effective when used for patients at
high‑risk of arrhythmic death and low‑risk of other causes of death.
Specific patient populations are now recognized for whom the benefit of ICD therapy outweighs any risks
Categorizing patients on the basis of only LVEF and NYHA Functional Class can aid in identification of patients who have highest benefit from primary preventions
Thank You