1. ICD FOR PRIMARY PREVENTION EVIDENCE REVIEW
DR SANDEEP.R
SR CARDIO

2. INTRODUCTION
The implantable cardioverter defibrillator (ICD) is a battery-powered implantable device that can detect and terminate potentially life-threatening tachyarrhythmias via defibrillation or antitachycardia pacing to prevent SCD
Sudden cardiac death (SCD) remains the leading cause of death
ICD has been recommended for secondary prevention of sudden cardiac death based on several RCT

3. But only a small percentage of patients who suffer cardiac arrest survive to benefit from the ICD therapy as secondary prevention
Thus prophylactic use of ICD for primary prevention of SCD becomes an attractive option for high-risk patients

4. ICD IN ISCHAEMIC CARDIOMYOPATHY

5. MADIT I (The Multicenter Automatic DefibrillatorImplantation Trial)
32 hospital centers (30 in the United States and 2 in Europe)
Study period
The first MADIT I trial randomized subjects with prior MI, spontaneous NSVT, LVEF 35%, and inducible VT refractory
to intravenous procainamide administration into either the
ICD group or the conventional therapy group. 11
MADIT I was prematurely aborted after enrolling only 196 patients when preliminary analysis revealed a significant benefit of ICD therapy in reduction of overall mortality by 54%.
(N Engl J Med1996;335: )

6. MADIT I (The Multicenter Automatic DefibrillatorImplantation Trial)
INCLUSION CRITERIA
EXCLUSION CRITERIA
NYHA I, II, or III with prior M.I
Previous cardiac arrest or VT causing syncope that was not associated with AMI
LVEF < 0.35
Acute Myocardial infarction < 3 weeks
Documented episode of asymptomatic unsustained VT
Patients who underwent CABG within the past two months or PTCA within the past three months
Inducible, nonsuppressible VT on EP study
Symptomatic hypotension while in a stable rhythm
Had no CABG /PTCA in last 3 mths

7. MADIT I (The Multicenter Automatic DefibrillatorImplantation Trial)
Two patient groups (1:1) randomization  1. Conventional Medical Therapy (CMT)  2.ICD
Mean follow up 27 months
Primary endpoint: All cause Mortality

10. RESULTS CONCLUSION 54% reduction in all cause mortality in ICD group
No evidence for of mortality benefit with amiodarone ,betablockers

11. CABG Patch trial The Coronary Artery Bypass Graft (CABG) Patch trial
The trial was conducted at 37 clinical centers, 35 in the US & 2 in Germany
INCLUSION CRITERIA
< 80 yrs age
LVEF< 0.36
Abnormalities on a signal-
averaged electrocardiogram
Study period –
900 patients who came for elective CABG were randomized into ICD ( 446) VS no ICD group ( 454)
(duration of the filtered QRS com-
plex,
114 msec; root-mean-square voltage in the terminal 40
msec of the QRS complex, 20 m
V; or duration of the terminal
filtered QRS complex at 40 V,
38 msec).
The primary endpoint was all-cause mortality

12. RESULTS
CONCLUSION
No evidence of improved survival among patients with coronary heart disease, a depressed LVEF , and an abnormal signal-averaged ECG in whom a defibrillator was implanted prophylactically at the time of elective CABG

13. Buxton AE. N Engl J Med 1999;341:1882-90
MUSTT Buxton AE. N Engl J Med 1999;341: (Multicentre UnSustained Tachycardia Trial)
The trial was designed to study the concept of guiding the management of high risk patients with the results of EPS
Not primarily designed as a randomized ICD clinical trial
AIM: To evaluate the efficacy of antiarrhythmic therapy guided by EP testing in reducing the risk of SCD and cardiac arrest among patients with CAD, LV dysfunction, and asymptomatic, unsustained VT
STUDY PERIOD & median follow-up of 39 months
Buxton AE. N Engl J Med 1999;341:

14. METHODOLOGY INCLUSION CRITERIA EXCLUSION CRITERIA
Patients with CAD
H/O syncope/sustained VT/VF > 48hrs of MI
LVEF<40%
NSVT due to metabolic causes
Asymptomatic, unsustained VT
Symptomatic, unsustained VT
Patients in whom sustained VT were induced by programmed stimulation

15. STUDY PROTOCOL Primary Endpoint Arrhythmic death or cardiac arrest
Secondary Endpoints
Total mortality
Cardiac mortality
Spontaneous, sustained VT

16. MUSTT EP-Guided Rx Patients
Treatment at Discharge
No Rx 7%
ICD
46% IA
26%
Sotalol 9%
Amiodarone
10%
Antiarrhythmic Drugs: 45%
Buxton AE. N Engl J Med 1999;341: 35

17. Results -Arrhythmic Death or Cardiac Arrest
No EP-Guided AA Rx
EP-Guided Rx, (No ICD and ICD)
p = 0.04
0.5
0.4
Event Rate
0.3
0.2
0.1 1 2 3 4 5
Time after Enrollment (Years)
Buxton AE. N Engl J Med 1999;341: 17

20. Results
The two-year (12 versus 18 percent) and five-year (25 versus 32 percent) rates for the primary endpoint were significantly lower for EPS guided therapy compared to no therapy
There was a nearly significant reduction in the secondary endpoint of total mortality at five years in the group receiving EPS guided therapy (42 versus 48 percent, p = 0.06).
The reduction in the primary and secondary endpoints in the EPS guided group was largely attributable to ICD therapy
At five years the primary endpoint occurred in 9 percent of those receiving an ICD compared with 37 percent of those receiving an antiarrhythmic drug, and the secondary endpoint occurred in 24 and 55 percent respectively.
There was no difference in outcome between patients receiving no therapy and those treated with an antiarrhythmic drug

21. CONCLUSION
Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators but not with antiarrhythmic drugs reduces the risk of sudden death in high-risk patients with coronary disease
At 5 years, there were absolute reductions in total
mortality of 31% in the patients receiving ICD therapy when
compared with those receiving pharmacological therapy and
of 24% when compared with those receiving no therapy

22. MADIT II
INCLUSION
EXCLUSION
M.I >4 WEEKS
Revascularization within the preceding three months
LVEF <30%
M.I < 3 weeks
New York Heart Association
functional class IV at enrollment
AIM: To evaluate the potential survival benefit of a prophylactically implanted defibrillator (in the absence of electrophysiological testing to induce arrhythmias) in patients with a prior M.I and LVEF< 0.30
Enrolled patients from 76 hospital centers (71 US and 5 in Europe)
STUDY PERIOD
PRIMARY OUTCOME ALL CAUSE MORTALITY
N Engl J Med, Vol. 346, No. 12

23. Implantable defibrillator Conventional medical therapy
MADIT II: Study Design
1232 Patients with prior MI more than 30 days and LVEF < 30% randomized in a 3:2 ratio
Implantable defibrillator
(n=742)
Conventional medical therapy
(n=490)
All Cause Mortality - Average follow-up of 20 months
Stopped early

25. RESULTS

26. MADIT II: All-Cause Mortality
Death
Avg. follow-up=20 months
P=0.016
Hazard
Ratio = 0.65
Conventional
Therapy
ICD

27. MADIT II: Mortality Events
Non Cardiac
Cardiac
Arrhythmic
Non Arrhythmic
Conv
Therapy
ICD
Conv
Therapy
Conv
Therapy
Conv
Therapy
ICD
ICD
ICD

28. New or Worsening Heart Failure
MADIT II: CHF
New or Worsening Heart Failure
P=0.09
Conventional
Therapy
ICD

29. RESULTS
INTERESTING FACTS:
In the current study the survival benefit began approximately nine months after the device was implanted
No ep study used
Increased incidence of heart failure in ICD group
REASONS FOR HEART FAILURE
1. INCREASED SURVIVAL
2.SHOCK INDUCED MYOCARDIAL INJURY
3.LONG TERM PACING INDUCED DYSFUNCTION
CONCLUSION
In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy

30. SCD HeFT INCLUSION CRITERIA Patients >18 years of age
NYHA class II or III
Stable CHF due to ischemic or non ischemic causes & LVEF < 35 percent
Study period
The primary end point of the trial was death from any cause
N=2521
The etiology of cardiomyopathy was ischemic in 52 percent and nonischemic in 48 percent

31. 40 months average follow- up
SCD-HeFT - Protocol
Inclusion criteria
Placebo n=847
Amiodarone n=845
ICD implant n=829
40 months average follow- up
Optimize: B, ACE-I, Diuretics
1 Bardy GH. Chapter Excerpt from Arrhythmia Treatment and Therapy. Woosley RL, Singh SN, editors. Marcel Dekker, 1st edition. 2000;

32. RESULTS

33. RESULTS

34. RESULTS ICD therapy had a signifi-
cant benefit in patients in NYHA class II but not in
those in NYHA class III CHF. In contrast, amioda-
rone therapy had no benefit in patients in NYHA class II and decreased survival among patients in NYHA class III CHF, as compared with those whO received placebo

35. SCD-HeFT -Results
In NYHA Class II or III HF patients with EF < 35% on good background therapy, the mortality rate for placebo-controlled patients is 7.2% per year over 5 years
Simple, shock-only ICDs decrease mortality by 23% (p=0.007) & the benefit did not vary according to the cause of CHF
Amiodarone, when used as a primary preventative agent, does not improve survival
Dr. Bardy’s conclusions from the ACC-latebreaking clinical trial were:
In NYHA Class II or III HF patients with EF < 35% on good background therapy, the mortality rate for placebo-controlled patients is 7.2% per year over 5 years
Simple, shock-only ICDs decrease mortality by 23% (p=0.007)
Amiodarone, when used as a primary preventative agent, does not improve survival

36. EARLY POST MI TRIALS
DINAMIT
IRIS

37. DINAMIT The Defibrillator in Acute Myocardial Infarction Trial
Evaluated the role of prophylactic ICD implantation compared to no ICD
Inclusion criteria
674 patients with MI in the preceding 6 to 40 days (mean 18 days)
LVEF ≤35 percent
Reduced heart rate variability or elevated resting heart rate (≥80beats/min).
Exclusion criteria
Patients with sustained VT >48 hours post-MI, NYHA class IV HF, or coronary artery bypass grafting (CABG) or three-vessel percutaneous coronary intervention post-MI
Mean follow-up was 30 months.
NEJM 2004:351:2481-8

39. RESULTS

40. RESULTS

41. IRIS trial Immediate Risk Stratification Improves Survival
Enrolled 898 patients
Inclusion criteria:
MI within the preceding 5 to 31 days and one or both of the following two criteria:
LVEF ≤40 percent and a resting HR ≥90 beats/min
Nonsustained VT at a rate ≥150 beats/min
Mean follow-up months

42. RESULTS:
No difference in all-cause mortality between patients randomly assigned to ICD therapy VS medical therapy.
The rate of SCD higher in the control group
The number of non sudden cardiac deaths higher in the ICD arm

43. Significant recovery of ventricular function may have occurred in some of the patients which would dilute the long-term benefit of the ICD in such patients.
Some SCD events in the early postinfarction period may have been due to recurrent ischemia which would not be definitively treated by ICD discharge
ICD implantation might impose additional risk in these patients immediately post-MI.
The enrollment requirements of reduced heart rate variability in DINAMIT and resting heart rate ≥90 beats/min in IRIS could have selected a group of patients with a high mortality from nonarrhythmic causes .

44. COMPARISON OF TRIALS

45. ICD IN NONISCHAEMIC CMPY

46. DEFINITE Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation
STUDY PERIOD –
LVEF < 36%
Nonischemic DCMPY
PVCs or NSVT
INCLUSION CRITERIA
The primary end point of the study was death from any cause
Sudden death from arrhythmia was a pre-
specified secondary end point
N=458
RANDOMIZATION
Ambient arrhythmias were defined by
an episode of nonsustained ventricular tachycardia
on Holter or telemetric monitoring (3 to 15 beats at a rate of more than 120 beats per minute) or an average of at least 10 premature ventricular complexes per hour on 24-hour Holter monitoring
N=229
standard medical therapy + ICD
EXCLUSION CRITERIA
NYHA CLASS IV
THOSE WITH PPI
HEART TRANSPLANT ELIGIBLE
N=229
standard medical therapy
N Engl J Med 2004;350:

47. RESULTS HR for death from any cause was 0.65 (95% C.I 0.40 to 1.06)
HR for sudden death from arrhythmia was (95 % C.I 0.06 to 0.71)

48. RESULTS

49. RESULTS

50. COMPARISON OF TRIALS

51. ICD COMBINED WITH CRT

52. COMPANION trial — The Comparison Of Medical Therapy, Pacing, And Defibrillation In Heart Failure (COMPANION) trial
1520 patients
NYHA class III-IV HF
LVEF ≤35 percent
Lbbb > 120 msec
Nearly half of all patients enrolled had a nonischemic etiology of HF.
Randomly assigned to optimal medical therapy, CRT alone, or CRT+ICD
The primary end point was a composite of death from any cause or hospitalization for any cause
Secondary end point - death from any cause
NEJM 350:21 MAY 2004

55. Results
CRT+ICD , as compared with optimal pharmacologic therapy, was associated with a 27% reduction in the risk of death from any cause in the subgroup with ischemic CMPY (HR for death, 0.73; 95% C.I, 0.52 to 1.04) & a 50 %reduction in nonischemic CMPY
CONCLUSION
Patients with advanced heart failure and a prolonged QRS interval, CRT decreases the combined risk of death from any cause or first hospitalization and, when combined with an ICD, significantly reduces mortality

56. EPS
MADIT
MADIT II
MUSTT
LVEF
SCD-HeFT
COMPANION
QRS≥120

57. PVC
NSVT
DEFINITE
LVEF
SCD-HeFT
COMPANION
QRS≥120

62. Long-QTS HCM ARVC Brugada CPVT Rec syncope on drug, sustained V arrhy
Spont sust VT, spont NSVT, f/h SCD, syncope, LV thick ≥30mm, abn BP response to exercise
ARVC
Induction VT in EPS, detection of NSVT on holter, male, severe RV dilation, extensive RV involvement, <5 at presentation, LV involvement, unexplained Syncope, genotypes
Brugada
Syncope / documented VT
CPVT
Syncope / documented VT on βBlockers

63. THANK YOU