1. Primary prevention of SCD using ICD- Review of literature
Dr Frijo Jose A

3. Risk stratification for ICD therapy
Incidence of SCD in unselected adult population- only 2 per 1000 p/yr
Currently, LVEF- 1⁰ factor to select pts for ICD
SAECG, baseline V arrhythmia, T alternans, autonomic function, EP

4. Non-invasive evaluation for SCD
Cardiovascular function
h/o syncope
Ventricular arrhythmias
ECG
Autonomic function evaluation
Serum markers
Invasive evaluation of SCD
EPS

5. Cardiovascular function
LVEF- most consistent & powerful predictor of all-cause & cardiac mortality in IHD & DCMP
NYHA- Despite subjective, imprecise- simple bedside potent risk-stratification tool
Degree of NYHA class- Not linearly related
NYHA classes II & III - much more likely arrhythmia than class IV

8. Pts with NYHA IV CCF- very ↑mortality from progressive pump failure
Therefore, such pts not usually considered appropriate candidates for ICD therapy
Primary prevention ICD trials have excluded pts with NYHA IV

9. Pts with syncope have high risk of SCA
In CCF pts with a h/o syncope- incidence of SCD - 45%, V/S incidence 12% in pts with no h/o syncope (p< )
Middlekauff etal. Syncope in advanced heart failure:
high risk of sudden death regardless of origin of syncope
.J Am Coll Cardiol 1993;21:110 –116

10. Ventricular arrhythmias
PVC & NSVT in established SHD- risk marker of SCD- magnitude varies with nature & extent of underlying diseases
IHD- freq & repetitiveness of PVCs, + ↓ LVEF (<30%)- high risk of SCD (Bigger et al- Circulation 1984;69:250–8)
Length but not rate of NSVT- predictor of major arrhythmias in DCM
3–4 beat runs of NSVT- similar arrhythmia-free survival as pts without NSVT , but incidence of major arrhythmias ↑to 10% per yr in 10 beat runs NSVT (P<0.05). (Grimm et al- Pacing Clin Electrophysiol 2005;28:S207–10)

12. Standard ECG
Prolonged QRS duration (usually ≥120 ms) and repolarization abn- independent predictors of SCD
Prolonged QTc(>420 ms, esp long-QT synd) and familial short-QTc (≤300 ms) indicate an ↑risk of SCD

13. Microvolt T-wave alternans
ABCD trial-
Positive & negative predictive values of MTWA similar to EPS at 1 year
MTWA & EPS have synergistic value
MASTER-I
MTWA did not predict life-threatening ventricular tachyin 575 post-MI with LVEF <30%-but appear to predict all-cause mortality

14. SAECG MUSTT -SAECG strong predictor of arrhy death & total mortality
SAECG- excellent - predictive value in IHD, + predictive value is low –limits in preventive therapy
DCM- available data conflicting-
MACAS trial –abn SAECG not helpful for arrhythmic risk prediction. (Grimm et al. Marburg cardiomyopathy study. Circulation 2003;108:2883–91)

15. Serum markers BNP might be useful
521 survivors of AMI- BNP potent predictor even after adjusting for other clinical variables, inclu LVEF. (Tapanainen et al. J Am Coll Cardiol 2004;43:757–63)
121 ICD recipients with MI -↑BNP and CRP- asso ↑VT incidence. (Blangy et al. Europace 2007;9:724–9)
BNP is primarily a marker of progressive CHF, which itself may lead to ↑arrhyth- role of BNP- more studies are needed

16. Invasive evaluation of SCD
IHD- inducibility of sustained V tachy during EPS- well-established marker of SCD
Limitations-
Relatively high number of false-negative- Non-inducibility of VT may not imply a lack of risk
DCM-value of EPS- controversial

17. Multicenter Automatic Defibrillator Implantation Trial (MADIT, now called MADIT-I)

18. 196 pts-
NYHA- I, II, III with prior MI (≥3/52); LVEF ≤0.35; a documented asymptomatic unsustained VT; and inducible, nonsuppressible VT on EPS
Sustained VT/VF reproducibly induced & not suppressed after IV procainamide
CABG <2/12 or PTCA <3/12 were excluded
ICD (n ) V/S conventional medical therapy (n-101)
Death from any cause- end point

19. Average follow-up- 27/12
ICD- 15 Ds (11card) V/S Convnt- 39 Ds (27card)
Hazard ratio for overall mortality- 0.46
Relative risk reduction of 54% with ICD

21. Subset analysis Survival benefit from ICD- only in high-risk pts
LVEF <26%, HF requiring therapy, QRS ≥ 120
Benefit ↑progressively as a function of no of risk factors- greatest reduction in mortality with ICD in those with 2 (HR 0.30) or 3 risk factors (HR 0.20)

22. MUSTT Multicenter Unsustained Tachycardia Trial Buxton AE
MUSTT Multicenter Unsustained Tachycardia Trial Buxton AE. N Engl J Med 1999;341:
The trial was designed to study the concept of guiding the management of high risk patients with the results of EPS
Was not primarily designed as a randomized ICD clinical trial

23. Primary endpoint: Median follow-up- 39/12 CAD (1/12 - 3yrs)
EF < 0.40 NYHA I,II,III
Asymptomatic nonsustained VT
Primary endpoint:
Arrhythmic death or cardiac arrest
Median follow-up- 39/12

24. 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

25. MUSTT Randomized Patient Results Arrhythmic Death or Cardiac Arrest
0.5
No EP-Guided AA Rx
EP-Guided Rx, (No ICD and ICD)
p = 0.04
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

26. MUSTT Randomized Patient Results Arrhythmic Death or Cardiac Arrest
0.5
EP-Guided Rx, No ICD
No EP-Guided AA Rx
EP-Guided Rx, ICD
p < 0.001
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: 18

28. Relative Risk Reduction with ICD Rx (95% CI)
End
Point
As Compared To:
EP Guided Rx
With No ICD
No EP
Guided Rx
Cardiac arrest or death from arrhythmia
76%
(55%-87%)
73%
(53%-85%)
Death from all causes
60%
(41%-73%)
55%
(37%-68%)

29. MADIT-II

30. 1232 pts with a prior MI (≥1/12) & LVEF ≤0.30
NYHA-I,II,III
ICD (742) V/S conventional (490)
Invasive EPS not required
End point- Death from any cause

31. Average follow-up- 20/12
Mortality rates-
19.8%- conventional
14.2%- ICD
HR for risk of any cause death in ICD V/S conventional (P=0.016)
As compared with conventional , ICD asso with 31% reduction in risk of death

35. At 8 years of follow-up
Cumulative probability of all-cause mortality - 49% among ICD V/S 62% among non-ICD (P0.001)
ICD asso with signi long-term survival benefit (HR- 0.66; P0.001)

36. ICD Benefit by Device Pacing Type

37. Dual-chamber ICDs were programmed to active DDD pacing in MADIT-II regardless of conduction abnormalities as at the time of the study it was hypothesized that AV sequential pacing improves CCF sympts
Dual Chamber and VVI Implantable Defibrillator (DAVID) trial- high frequency of RV pacing with dual-chamber ICD- contributing factor to ↑CCF events & mortality

38. SCD-HeFT

39. 2521 pts
NYHA class II (70%)or III (30%) & LVEF ≤35%
IHD-52%, DCM-48%
Conventional plus placebo (847)
Conventional plus amiodarone (845)
Conventional plus single-lead ICD (829)

40. Median follow-up- 45.5/12
Placebo- 244 deaths (29%), Amio (28%), ICD- 182 (22%)
Placeb V/S Amio- Similar death risk (HR-1.06;P=0.53)
Placeb V/S ICD- ↓ death risk of 23% (HR-0.77;P=0.007)
Hence, ICD ↓overall mortality by 23%
Results did not vary according to either ischemic or nonischemic causes of CHF

42. Madit 2- similar
Definite nyha 3 best

43. CABG PATCH-TRIAL

44. Elective CABG-900 -ICD(446) or Control(454)
LVEF <0.36, and abn on SAECG
Average follow-
up of 32/12
ICD- 101 deaths (71cardiac), Control- 95 (72)
HR for death from any cause (P-0.64)

46. No evidence of improved survival among CAD pts + ↓LVEF + abn SAECG in whom a ICD was implanted prophylactically at the time of elective CABG

47. DINAMIT

48. ICD (332) V/S no ICD (342)
6-40 days after a MI
LVEF ≤0.35 and impaired cardiac autonomic function (↓HR variability or ↑average 24-hr HR on Holter)
mean follow-up -30/12
No diff in overall mortality betw gps
Although ICD asso with ↓in the rate of death due to arrhythmia, that was offset by ↑in rate of death from nonarrhythmic causes

49. DCM

50. CAT

51. Recent onset DCM (9/12) and LVEF <30%
ICD V/S no ICD
The trial was terminated after the inclusion of 104 pts because all-cause mortality rate at 1 year did not reach expected 30% in control
Mean follow-up 5.5yrs- 30 deaths (13-ICD, 17-control)
Cumulative survival was not significantly different between the two groups (93% and 80% in control V/S 92% and 86% in ICD after 2 and 4 yrs, resp)

52. AMIOVIRT

53. 103 DCM, LVEF <0.35, and asymptomatic NSVT - Amiodarone V/S ICD
Primary end point - total mortality
Survival at 1 yr (90% vs. 96%) and 3 yrs (88% vs. 87%) in the amiodarone and ICD, respectively- not stat different (p=0.8)
The study was stopped

54. DEFINITE

55. 458 dcm pts with LVEF<36% and
PVC(>10/hr) / NSVT
NYHA I,II,III
229 -medi, 229 –medi + single-chamber ICD
Followed for mean – 29/12

56. 68 deaths: 28-ICD V/S 40 med (HR-0.65;P=0.08)
Statistical signi not reached, but strong trend toward ↓of mortality with ICD (p=0.08)
Mortality rate 2yrs- 14.1% med V/S 7.9% ICD
17 SCD from arrhythmia: 3 ICD V/S 14 med (HR- 0.20; P=0.006)

59. SCD-HeFT

60. COMPANION

61. NYHA IIIorIV , IHD/DCM , QRS >120ms
Optimal pharmac alone / combi with CRT with either a PPI / ICD
CRT with an ICD signi reduced all-cause mortality V/S pharmac alone (HR- .50)

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

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

68. 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 βB

69. Thank you…