Sudden Cardiac Deathmanagement challenges of a global problem

Zayd A. Eldadah, MD, PhD

Co-Director, Cardiac Electrophysiology, Washington Hospital Center

Director, Cardiac Electrophysiology, Georgetown University Hospital

Washington DC

NAAMA International Medical Convention ● Beirut ● 26 June 2010

I have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. I will inform the audience of any off-label uses discussed.

Name of Presenter: Zayd A. Eldadah, MD, PhD

Affiliation/Financial Interest Organization Grant/Research Support Medtronic, St. Jude Medical,

Boston Scientific

Consultant Boston Scientific

NAAMA’s 24th International Medical ConventionMedicine in the Next Decade: Challenges and Opportunities

Beirut, LebanonJune 26 – July 2, 2010

Objectives

Recognize the public health

significance of sudden cardiac death

Review the preventive role of ICD

therapy

Recognize challenges to global

prevention of sudden cardiac death,

particularly in the developing world

Case Presentation

69 year-old academic cardiologist with no

documented cardiac history

– Non-smoker, non-diabetic, mild hypertension

– An avid bicyclist

– Exercised regularly, robust & active life

– Particular fondness for Lebanese cuisine and

Arab history

Case Presentation

69 year-old academic cardiologist with no

documented cardiac history

– Found dead on his favorite bicycling route

(with his feet still clipped in the bicycle

pedals)

– Autopsy showed enlarged heart, coronary

atherosclerosis, but no infarct

– Office desk drawers later found to be filled

with antacids

Sudden Cardiac Death

Unexpected death due to cardiac cause

Abrupt loss of consciousness within one

hour of the onset of acute symptoms

If unwitnessed, death within 24 hours of

being last known alive & asymptomatic

Sudden Cardiac Death

Traditional estimate: ~1 SCD per 1,000

population per year in the U.S. and Western

Europe

Japanese data: ~1-2 SCDs per 1,000

population per year

Single-county prospective study in Oregon:

0.53 SCDs per 1,000 population

Smith and Cain. J Interv Card Electrophysiol. 2006.

Chugh, et al. J Am Coll Cardiol. 2004

Global All-Cause Death

58 million deaths worldwide (2005)

– ~1% of human population

Non-communicable diseases (cardiac,

cancer, etc.): 60% of all deaths

Cardiovascular disease is the leading

cause of non-communicable human

mortality

– 17 million (30% of all global deaths)World Health Organization. 2005

The leading cause of death in developed countries:

1. Myerberg RJ, Catellanos A. Cardiac Arrest and Sudden Cardiac Death. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 5th Ed. New York: WB Saunders. 1997: 742-779.

2. Circulation. 2001; 104: 2158-2163.

3. Vreede-Swagemakers JJ et al. J Am Coll Cardiol 1997; 30: 1500-1505.

4. MMWR Vol. 51 Feb 15, 2002.

Sudden Cardiac Death

An increasing cause of death in developing countries

High recurrence rate

Vast majority (>75%) due to VT / VF

<5%~400,0003W. Europe

5%~300,0002U.S.

<1%3.5m – 7.0m1Worldwide

SurvivalIncidence(cases/year)

Ventricular Tachycardia

Ventricular Fibrillation

1. U.S. Census Bureau, Statistical Abstract of the United States: 2001.

2. American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001.

3. 2002 Heart and Stroke Statistical Update, American Heart Association.

4. Circulation. 2001;104:2158-2163.

SCD in the U.S.impact relative to other major killers

1 2 2 3 4

0

100,000

200,000

300,000

400,000

500,000

AIDS Breast

Cancer

Lung

Cancer

Stroke SCD

# d

ea

ths

/ye

ar

Implantable Cardioverter-Defibrillator (ICD)

Michel Mirowski

(1924-1990)

ICD therapy for SCD

Highly effective secondary prevention

– AVID

Eight clinical trials assessed efficacy of ICD

as primary prevention:

MADIT-I, MADIT-II, SCD-HeFT, DEFINITE,

DINAMIT, COMPANION, CABG-Patch,

MUSTT

Meta-analysis: primary-prevention ICDs

reduce mortality by 28% at two years vs.

conventional therapyAVID Investigators. N Engl J Med. 1997.

Moss. Circulation. 2005.

ICD Implant Criteria ACC/AHA Guidelines

Resuscitated VF / hemodynamically

unstable VT (Class I)

Ischemic or non-ischemic cardiomyopathy,

LVEF ≤35%, NYHA Class II-III (Class I)

Ischemic or non-ischemic cardiomyopathy,

LVEF ≤35%, NYHA Class I

– Class IIa evidence for ischemic cardiomyopathy

– Class IIb evidence for non-ischemic

cardiomyopathy

Sudden Cardiac Death Incidence and LVEF

0

1

2

3

4

5

6

7

8

0-30% 31-40% 41-50% >50%

Vreede-Swagemakers JJ. J Am Coll Cardiol. 1997;30:1500-1505.LVEF

% S

CD

Vic

tim

s

7.5%

5.1%

2.8%

1.4%

For post-infarct

patients, mean

interval between

MI and SCD: 6.5

years

Sudden Cardiac Death in the general population

adapted from Myerburg et al, Circulation 1998; 97:1514

00 100100 200200 300300

x1,000x1,000

Incidence (%/Year)Incidence (%/Year) Total Events (No./Year)Total Events (No./Year)

General adultGeneral adult

populationpopulation

MultiriskMultirisk

subgroupsubgroup

Any previousAny previous

coronary eventcoronary event

EF <35% orEF <35% or

heart failureheart failure

Cardiac arrest,Cardiac arrest,

VF/VT survivorsVF/VT survivors

00

High-risk post-MIHigh-risk post-MI

subgroupssubgroups

11 22 55 1010 2020 40403030 00 100100 200200 300300

x1,000x1,000

Incidence (%/Year)Incidence (%/Year)

General adultGeneral adult

populationpopulation

MultiriskMultirisk

subgroupsubgroup

Any previousAny previous

coronary eventcoronary event

EF <35% orEF <35% or

heart failureheart failure

Cardiac arrest,Cardiac arrest,

VF/VT survivorsVF/VT survivors

00

High-risk post-MIHigh-risk post-MI

subgroupssubgroups

11 22 55 1010 2020 40403030

~450,000

00 100100 200200 300300

x1,000x1,000

Incidence (%/Year)Incidence (%/Year)

General adultGeneral adult

populationpopulation

MultiriskMultirisk

subgroupsubgroup

Any previousAny previous

coronary eventcoronary event

EF <35% orEF <35% or

Cardiac arrest,Cardiac arrest,

VF/VT survivorsVF/VT survivors

00

High-risk post-MIHigh-risk post-MI

subgroupssubgroups

11 22 55 1010 2020 40403030

MADIT-II, SCD-HeFT,COMPANION

CARE-HF

ICD ChallengesPicking the Population to Treat

LVEF as a risk marker

– a crude criterion alone

– will not capture the majority of SCDs

Risk-stratification and cost-effectiveness

strategies are direly needed, particularly

in developing countries.

ICD ChallengesUnder-Use of Therapy in U.S.

In 49,517 SCD survivors, only 31%

received an ICD before discharge

U.S. CMS & Managed Care data:

– 1,226 per million population found to be

ICD candidates (ventricular arrhythmia or

SCD)

– Yet actual ICD use rate is 416 per million

In 20,511 potentially eligible HF patients,

only 33% received ICD before dischargeVoigt, et al. J Am Coll Cardiol. 2004.

Ruskin, et al. J Cardiovasc Electrophysiol. 2002.

Hernandez et al. JAMA. 2007.

ICD Challenges Gender, Race, Ethnicity Disparities in ICD Therapy

Hernandez, et al. JAMA. 2007

-27%

Compared to ICD Usage Rates in White Men:

African-American Men

-38%

-48%

White Women

African-American Women

Global ICD Usage

2005 World Survey of Cardiac Pacing and ICDs. Mond et al. PACE. 2008

New New Implants

Americas Implants per million population

Argentina 672 18

Brazil 1,413 8

Canada 3,000 91

USA 119,121 401

Global ICD Usage

World Survey of Cardiac Pacing and ICDs. Mond et al. PACE. 2008

New New Implants

Europe Implants per million population

Belgium 846 82

Denmark 540 105

Greece 345 31

Italy 7,439 129

Russia 151 2

Spain 1,400 32

Sweden 412 46

Switzerland 627 84

United Kingdom 2,835 47

Global ICD Usage

World Survey of Cardiac Pacing and ICDs. Mond et al. PACE. 2008

New New Implants

Asia Implants per million population

Australia 2,864 142

China 186 <<1

Hong Kong 211 28

India 415 <<1

Japan 2,360 19

South Korea 148 3

Global ICD Usage

World Survey of Cardiac Pacing and ICDs. Mond et al. PACE. 2008

New New Implants

Middle East / Africa Implants per million population

UAE 13 4

Iran 314 5

Israel 683 98

South Africa 105 2

~80% of the global mortality of SCD

is in middle- to low-income countries

ICD Challengeseconomics

Individual ‘cost’ of SCD incalcuable

Population cost can be measured as Quality-

Adjusted Life Years (QALY) gained

Six-trial analysis (MADIT-1, MADIT-2, MUSTT, SCD-

HeFT, DEFINITE, COMPANION)

– ICDs added 1.01-2.99 QALYs

– Costs ranged from $34,000 - $70,200 per QALY

gained

– Viable in developed economies, but not elsewhereSanders, et al. N Engl J Med. 2005

Challenges to Global SCD Therapy

Overcoming barriers to ICD therapy

– Education (patients, caregivers, broader

population)

– Enhancing safety of implants

– Employing strategies to minimize

inappropriate shocks

Strategies for resource-limited populations:

– Primary prevention with risk-factor modification (e.g., diet and anti-smoking campaigns)

– Genomic-based risk stratification

– Improving EMS, medical, and transportation infrastructure

– Home-based automatic external defibrillators (AEDs) for high-risk patients

– Reducing therapy costs (e.g., simpler devices, reused devices)

Challenges to Global SCD Therapy

Summary

Sudden cardiac death is a major global public

health problem

Weakened hearts predispose to sudden death.

(Ejection Fraction ≤ 35%)

When added to optimal medical therapy, ICDs

reduce mortality in at-risk patients.

ICD therapy remains under-utilized

Effective strategies to address SCD will require

more education, better risk-stratification, and

creative focus on this worldwide killer