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