risk stratification of sudden cardiac...

Risk Stratification ofSudden Cardiac Death

Michael R Gold, MD, PhDMedical University of South Carolina

Charleston, SC USA

Disclosures: None

Sudden Cardiac DeathA Major Public Health Problem

> 1/2 of all cardiac deaths

1/6 of all deaths

> 400,000 SCD annually in US

Sustained Monomorphic VTVFAsystoleSudden Death Can Result From a Variety of Processes

Acute Ischemia Causing Ventricular Fibrillation

Sudden Death Can Result From a Variety of Processes

Complete Heart Block Ventricular Fibrillation


Pause – Dependent Torsade de PointesAssociated with Antifungal Drug


40 Years of ICD Technology

Engineering Tour de’ Force

ICDs in the Prevention of Death from Tachyarrhythmia Cardiac Arrest

AVID

80% CAD20% other

Secondary Prevention

The AVID Investigators NEJM 1997;337:1576

Secondary Prevention of SCD

AVID/CIDS/CASH Metaanalysis

EVENTS AT2 YEARS ICD

N=934AMIO

N=932H.R.

Deaths 200 255 .73p<0.001

Arrhythmic 61 117 .49p<0.001

Non - Arr 139 138 .93

Survival From Out-of-Hospital Cardiac Arrest

19%Seattle - 1982

30%AED

Seattle - 19880.8% (Blacks)2.6% (Whites) Chicago - 1998

14%Miami - 1974

7%AED

Miami - 2002

HAT Study Primary Endpoint

PAD Trial 993 Units 157 Residential (16%) 836 Public (84%)

Recreational facilities (28%) Shopping centers (28%) Entertainment complexes (10%) Community centers (8%) Large office buildings (8%) Other (hotels, factories, transit centers) (17%)

Hallstrom A, et al. N Engl J Med. 2004;351:637.

PAD Trial

Hallstrom A, et al. N Engl J Med. 2004;351:637.

Septadian Variability of SCD

Subpopulation on Beta Blockers

Influence of Race on SCD

Age-adjusted death rates (per 100,000 US population) for sudden cardiac death

Zheng Z. Circulation 2001

Years

Per 1

00,0

00 S

tand

ard

US

Popu

latio

n 600

500

400

300

200

100

0

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

African-American

White

American IndianAsian

Risk Stratification for SCD

Risk stratification of SCD has been studied for 40 years

The rule of 80 emerged–80% Male–80% VT/VF–80% CAD–80% LV dysfunction

More recent epidemiological studies have questioned these assumptions which are the foundation of preventative strategies

Sudden Cardiac DeathThe Maastricht Prospective Registry

1997-2000: 492 cases

Hx of CHF – 59 pts (12%)

In 54% (224 pts) cardiac arrest was the first manifestation of cardiac disease!

Gorgels et al. European Heart J, 2003; 24:1204

Sudden Cardiac DeathThe Maastricht Prospective Registry

Patients with Cardiac History: n=224

CAD - 171 (77%)

New MI – 10 (6%)

Prior MI – 113 (66%)

Time first MI to SCA – 9.7 ± 7.5 yrs

Prior Ant. MI – 37% Inf. MI – 53%

Gorgels et al. European Heart J, 2003; 24:1204

The Oregon Sudden Unexpected Death Study

2002-2004: 714 cases-Multnomah County, Oregon (pop.: 660,486)

EF measured prior to event in only 121 cases (17%)

Stecker et al. JACC, 2006; 47:1161

LV Ejection Fraction %

≤35% 30

36-54% 22

≥ 55% 48

Sudden Death-The Oregon Sudden Unexpected Death Study

Stecker et al. JACC, 2006; 47:1161

Patients with Known EF (121)

LVEF and SCA Incidence

012345678

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

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

LVEF

% S

CA

Vict

ims

7.5%

5.1%

2.8%

1.4%

Why is there a paradox between SCD and post MI Risk?

Gusto Study (n=2400)Angiographic substudyCardiac Cath 5-7 days post MI

– EF < 30% 4.3%– EF 30-40% 10.1%– EF > 40% 85.6%

Equivalent sudden deaths in EF <30% and EF > 40% groups even if 20-fold greater risk!

Non-Antiarrhythmic Drugs that Reduce Mortality and SCD

Beta BlockersACE InhibitorsARBsStatinsAldosterone AntagonistsASA

Antiarrhythmic Drugs that Reduce Mortality and SCD

MADIT I- Inclusion Criteria

CAD

LVEF < 35%

Nonsustained VT

Inducible VT (+ EPS)

MADIT I - Survival

1.0

0.8

0.6

0.4

0.2

0.00 1 2 3 4 5Year

Prob

abili

ty o

f sur

viva

l

Conventionaltherapy

Defibrillator

Moss AJ. N Engl J Med. 1996;335:1933-1940.

p=.009 at termination2 yr mortality 39% v 16%HR - 0.46

MUSTT Randomized Patient Results Total Mortality

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

Time after Enrollment (Years)0 1 2 3 4 5

0

0.1

0.2

0.3

0.4

0.5

0.6

Even

t Rat

e

p < 0.001

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

MADIT II - Eligibility Criteria

LVEF < 30% > 1 prior MI No arrhythmia req.

NYHA Class IV < 1 month from

acute MI CABG or PTCA

< 3 months Patients meeting

MADIT I criteria

Inclusion Exclusion

MADIT-II Survival

Moss AJ. N Engl J Med. 2002;346:877-83.

Defibrillator

Conventional

P = 0.007

1.0

0.9

0.8

0.7

0.6

0.0

Prob

abili

ty o

f Sur

viva

l

0 1 2 3 4

YearNo. At RiskDefibrillator 742 502 (0.91) 274 (0.94) 110 (0.78) 9Conventional 490 329 (0.90) 170 (0.78) 65 (0.69) 3

MADIT II – 8 Year Long Term Follow-up

Number Needed to Treat to save one life (NNT) and Life Years Saved (LYS) for all MADIT II patients (N=1232):

@ month 20 96

NNT 17 6

LYS 0.2 1.2

Death 31% 37%

• 2521 patients with either ischemic or NIDCM• NYHA Class II or III• EF < 35%• Single chamber ICDs – VVI 35/50bpm. Shock only 188 bpm• Amio/placebo drug or ICD/placebo drug

00

0.10.1

0.20.2

0.30.3

0.40.4

00 66 1212 1818 2424 3030 3636 4242 4848 5454 6060

Mor

talit

yM

orta

lity

Months of follow-upMonths of follow-up

AmiodaroneAmiodaroneICD TherapyICD TherapyPlaceboPlacebo

HR 97.5% CI P-ValueAmiodarone vs. Placebo 1.06 0.86, 1.30 0.529ICD Therapy vs. Placebo 0.77 0.62, 0.96 0.007

Mortality by Intention‐to‐treat

Follow-up: 45.5 monthsVital status: 100% known

N = 2,521

Sudden Cardiac Death

SCD-HeFTHeart Failure Trial

36.1%

28.9 %

34.0%

Bardy, NEJM 2005

DINAMIT

Hohnloser, S. et al. N Engl J Med 2004;351:2481-2488

• 674 Patients s/p Acute MI

• Single lead ICD• EF ~ 28%• 70% Q wave MI• Time to ICD

from MI -18 dy

Immediate Risk-Stratification Improves Survival (IRIS) StudyImmediate Risk-Stratification

Improves Survival (IRIS) Study

Steinbeck G, et al. N Engl J Med 2009;361:1427-36.

• Randomized comparison of ICDs vs. OMT 5-31 days after MI • LVEF ≤ 40%, HR > 90 +/- NSVT• No survival benefit with prophylactic ICD therapy

N=902 patients

Incremental Benefits with HF Therapies(Cumulative % Reduction in Odds of Death at 24 Months)

-28% to -49%P<0.0001

-54% to -71%P<0.0001

-68% to -81%P<0.0001

-75% to -86%P<0.0001

-77% to -88%P<0.0001

-72% to -87%P<0.0001

Fonarow GC, Yancy, CW. J Am Heart Assoc 2012;1:16-26.

Primary Prevention ICDs in Nonischemic Cardiomyopathy

• The role of ICDs among patients with ischemic cardiomyopathy was is well established, provided that it is not implanted early post‐MI

• Further expansion of ICD indications for patients with nonischemic cardiomyopathy was evaluated in a series of trials

• This included both narrow and wide QRS patients using conventional ICDs or CRT devices

DEFINITE – NIDCM

ICD – 229 ptsStandard -- 229 pts

P=0.08

HR 0.65 [95% CI, 0.40 to 1.06]

Follow up 29 +/- 14 months

• Age 58• 71% men• 23% DM• 25% AF• QRS 115 ms• LBBB 20%

Kadish A et al NEJM 2004;350:2151

• ACE/ARB 97%• -blockers 85%

DEFINITE

Sudden Death Mortality All-Cause Mortality in NYHA Class III

P=0.006 P=0.02

Kadish A et al NEJM 2004;350:2151

DEFINITE: ICDs in NIDCMNo required “time from HF diagnosis to enrollment”

< 3 mo(150)

Control 17.6%

ICD 7.3%HR = 0.37 (0.14‐0.99)

p =0.05

Kadish et al JACC 200663% RR

Early ICD Implants

00

0.10.1

0.20.2

0.30.3

0.40.4

00 66 1212 1818 2424 3030 3636 4242 4848 5454 6060

Mor

talit

yM

orta

lity


AmiodaroneAmiodaroneICD TherapyICD TherapyPlaceboPlacebo

HR 97.5% CI P-ValueAmiodarone vs. Placebo 1.06 0.86, 1.30 0.529ICD Therapy vs. Placebo 0.77 0.62, 0.96 0.007

Mortality by Intention‐to‐treat

Follow-up: 45.5 monthsVital status: 100% known

N = 2,521


SCD-HeFTHeart Failure Trial

36.1%

28.9 %

34.0%

Bardy, NEJM 2005

00

0.10.1

0.20.2

0.30.3

0.40.4

0.50.5

00 1212 2424 3636 4848 6060

Mor

talit

yM

orta

lity


ICD TherapyICD TherapyPlaceboPlacebo

00 1212 2424 3636 4848 6060Months of follow-upMonths of follow-up

Mortality by NYHA Class: ICD vs. Placebo

Class II Class III

HR 97.5% CI0.54 0.40, 0.74

HR 97.5% CI1.16 0.84, 1.61

32%

46%

20%

48%


SCD‐HeFTHeart Failure Trial

NYHA Class II - NNT = 8

Ischemic Etiology Non‐Ischemic Etiology

00

0.10.1

0.20.2

0.30.3

0.40.4

0.50.5

00 1212 2424 3636 4848 6060

Mor

talit

yM

orta

lity


ICD TherapyICD TherapyPlaceboPlacebo

00 1212 2424 3636 4848 6060Months of follow-upMonths of follow-up

Mortality by CHF Etiology

HR 97.5% CI0.79 0.60, 1.04

HR 97.5% CI0.73 0.50, 1.07

43%

21%

36%

28%



Mode of Death in SCD‐HeFT: ICD ‐ Placebo

02468

101214

Arrhythmic Heart Failure Other

ICDPlacebo

% D

eaths

37

95

66674.5%

11.2%

7.5%7.9%

p <0.001



9.6%

78

9.8%

83

Adapted from Packer D, et al HRS 2005

Total Deaths:ICD = 182Placebo = 244

*45.5 mo median f/u

0

100

200

300

400

500

600

II III Isch. N-Isch.

ICD implanted

VT/VF shock

21%25% 21% 24%

# of Pts

Class and etiology of CHF: VT/VF shocks

554

257

420 391

117 65 89 93

From: ACC/AHA/HRS Guideline Committee JACC 2008; 51: 2085-105

Classification of Recommendations for Device-Based Therapy

SIZE OF TREATMENT EFFECT

Class IBenefit > > > RiskProcedure/Treatment SHOULD be performed/administered

Class IIaBenefit > > RiskAdditional studies with focused objectives neededIT IS REASONABLE to perform procedure/administer treatment

Class IIBBenefit > RiskAdditional studies with broad objectives needed; additional registry data would be helpfulProcedure/TreatmentMAY BE CONSIDERED

Class IIIRisk > BenefitProcedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Danish NIDCM Trial

• NYHA class II or III, or NYHA class IV if CRT• LVEF ≤35%, > 200 pg/ml of NT‐proBNP• GDMT target doses of ACE/ARB and ‐blockers• PM or CRT‐P was not an exclusion• AF with HR resting over 100 bpm excluded• Dialysis excluded

Danish NIDCM Trial

• 1116 patients

• Randomized to ICD or “usual clinical care”

• Mean QRS: 146 ms (ICD); 145 ms (control)

• CRT: 58% (ICD); 58% (control)

Outcomes – All‐Cause Mortality

Outcomes

Cardiovascular Death Sudden Cardiac Death

Comparisons: DEFINITE, SCD‐HeFT, DANISH

DEFINITE SCD‐HeFT DANISH

ACE/ARB 96.7% 89% 97%

‐blockers 85% 78% 92%

Mineralocorticoid ? 30% 58%

Mortality: DEFINITE ‐ DANISH

DEFINITE CONTROL

DEFINITE ICD

Mortality Comparisons

SCD-HeFT CONTROL

SCD-HeFT ICD

COMPARISON OF REPORTED SCD RATES

Blue Dots

PARADIGM

DANISH

DANISH: Unusually low SCD rate:1.5% per year, only 35% of all deaths were sudden

DANISH TRIAL ‐ CONSIDERATIONS

• Selection Bias: Enrolled unusually low risk NIDCM patients– were the more ill already offered ICDs?

• Well – treated on GDMT• Outcome adulterated by CRT–Much higher % of CRT eligible patients enrolled than found in usual outpatient clinics (20‐25% v 60% in DANISH)

CARE-HFCARE-HF

409 383 358 338 209 85404 372 331 298 178 63

CRTMedical therapy

Number at risk

96

CRT

MedicalTherapy

0 400 16000.00

0.25

0.50

0.75

1.00Su

rviv

al

Time (days)800 1200

Hazard Ratio 0.60 (95% CI 0.47 to 0.77; P<0.0001)

COMPANION: All-Cause MortalityCOMPANION: All-Cause Mortality

From: Golwala H et al. Circulation 2017; 135: 201-203

All-cause Mortality in NICM Patients with Primary Prevention ICD or CRT

SUMMARYSCD remains a major cause of mortality in

the US and AsiaTreatment and Prevention of CAD and CHF

are important, including PCI and MedicationsICDs are the most effective therapy to

prevent SCD, but utililaztion remains lowICDs should be considered in ischemic

cardiomyopathy as well as dilated cardiomyopathy which persist with GDMT, despite the recent Danish Trial

risk stratification of sudden cardiac...

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