Primary prevention of SCD using ICD- Review of literature

Dr Frijo Jose A

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

• Non-invasive evaluation for SCD– Cardiovascular function– h/o syncope– Ventricular arrhythmias– ECG– Autonomic function evaluation– Serum markers

• Invasive evaluation of SCD– EPS

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

• 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

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<0.00001)

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

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)

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

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

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)

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

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

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

• 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-95-45+50) V/S conventional medical

therapy (n-101)• Death from any cause- end point

• 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

• 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)

MUSTTMulticenter Unsustained Tachycardia Trial

Buxton AE. N Engl J Med 1999;341:1882-90

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

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

No EP-Guided RxACE I & Beta-B locker

N=353

EP-Guided RxACE I & Beta-B locker

N=351

Inducible Sustained VTN=704

MUSTT EP-Guided Rx Patients Treatment at Discharge

Buxton AE. N Engl J Med 1999;341:1882-90.

Antiarrhythmic Drugs: 45%

No Rx

7%

ICD

46%

IA

26%

Sotalol

9%

Amiodarone

10%

MUSTT Randomized Patient Results Arrhythmic Death or Cardiac Arrest

Buxton AE. N Engl J Med 1999;341:1882-90.

No EP-Guided AA Rx EP-Guided Rx, (No ICD and ICD)

p = 0.04

Time after Enrollment (Years)

0 1 2 3 4 50

0.1

0.2

0.3

0.4

0.5

Ev

en

t R

ate

MUSTT Randomized Patient Results Arrhythmic Death or Cardiac Arrest

EP-Guided Rx, No ICD No EP-Guided AA RxEP-Guided Rx, ICD

p < 0.001

Time after Enrollment (Years)

0 1 2 3 4 50

0.1

0.2

0.3

0.4

0.5

Ev

en

t R

ate

Buxton AE. N Engl J Med 1999;341:1882-90.

Relative Risk Reduction with ICD Rx (95% CI)

EndPoint

As Compared To:EP Guided RxWith No ICD

As Compared To: 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%)

MADIT-II

• 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

• 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- 0.69 (P=0.016)• As compared with conventional , ICD asso with 31%

reduction in risk of death

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)

ICD Benefit by Device Pacing Type

• 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

SCD-HeFT

• 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)

• Median follow-up- 45.5/12• Placebo- 244 deaths (29%), Amio - 240 (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

• Madit 2- similar

• Definite nyha 3 best

CABG PATCH-TRIAL

• 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- 1.07 (P-0.64)

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

DINAMIT

• 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

DCM

CAT

• 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)

AMIOVIRT

• 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

DEFINITE

• 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

• 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)

SCD-HeFT

COMPANION

• 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)

MADIT

EPS

MUSTTMADIT IILVEF

SCD-HeFT

COMPANIONQRS≥120

DEFINITE

PVCNSVT

SCD-HeFT

COMPANION

LVEF

QRS≥120

• Long-QTS– Rec syncope on drug, sustained V arrhy

• HCM– 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

Thank you…