3. Occlusive Plaque rupture:
Sudden death, usually occurring within
minutes of the onset of chest pain, is the
first clinical manifestation of CAD in 20-
25% of patients
40% of deaths occur within 1h after
AMI
Kannel et al, Circulation 1975;51:606
4. Sudden Cardiac Death
General Adult (”Healthy”) Population
♦ Pathophysiology:
1) Coronary plaque rupture coronary occlusion
SCD
2) Electrical or mechanical abnormality
– WPW-syndrome
– Long QT-syndrome
– idiopatic VF, Brugada syndrome...
– HOCM, ARVD, myocarditis...
5. ”Why do some people die
when a coronary artery
suddenly occludes
……and others develop only a
myocardial infarction or UAP?”
7. Control
Single Cardiac Vagal Fiber Activity LAD
Occlusion and Risk of Sudden Death (Cats)
1
2
3
4 VF-
VF+
Occlusion
Imp/s P<0.01
Cerati et al 1991
8. Prevention of VF after Left Stellate
Ganglionectomy in Dogs
0
20
40
60
80
100 LSG
Control
20 min coronary occlusion
Puddu et al 1988
P=0.001
Survival
%
9. PTCA-model to Simulate Coronary
Occlusion
2 min coronary occlusion
≈ 500 pts
♦ Beat-to-beat RRi and BP
♦ Ventricular arrhythmias
♦ Repolarisation changes
♦ MSNA
↔Interventions: ß-blockade
α-stimulation
10. Continuous ECG, Heart Rate and BP Recordings
RR interval
(ms)
Blood
pressure
(mmHg)
RR interval
(ms)
Blood
pressure
(mmHg)
11. HRV and Sudden Cardiac Death
Malignant ventricular arrhythmias caused
by abrupt coronary occlusion
are a major cause of sudden death
20. HRV Responses and Site of Coronary Occlusion
66%
23%
11%
26%
11%
63%
26%
21%
53%
LAD LCX RCA
Airaksinen et al Am J Cardiol 1993
Vagus Vagus
21. Gender Difference in Autonomic and
Hemodynamic Reactions
Reactions in women versus men
Adjusted OR (95% CI)
Bradycardia 3.8 (1.6-8.9)
RMSD 1.8 (0.8-4.1)
Hypotension 2.6 (1.1-6.1)
B-J Reaction 25.6 (2.6-254)
VEBs 0.4 (0.2-1.3)
Airaksinen et al JACC 1998
22. Is a Mild Stenosis More Hazardous??
♦SCD is the 1st symptom of CAD in 20-25%
♦Experimental models:
Coronary occlusion VF
Tight stenosis:
♦Occlusion often asymptomatic
♦Restenosis: SCD infrequent
♦Reocclusion: 50% asymptomatic
23. Stenosis Severity and the Occurrence of
Ventricular Ectopic Activity During Acute
Coronary Occlusion
0
10
20
30
VPBs(%)
*
< 75 75-89 90-99
Stenosis severity (%)
Airaksinen et al Am J Cardiol 1995b
P<0.01
P<0.01
24. Effect of Preocclusion Stenosis Severity on
Heart Rate Reactions to Coronary
Occlusion
26%
42%
32%
83%
17%
≤ 85% > 85%
Severity of stenosis
Airaksinen et el Am J Cardiol 1994
Vagus
Vagus
25. Adaptation Phenomena
• Psychological adaptation helpful in experimental
models (Parker et al 1987)
• Missile War or earthquake: sharp rise in incidence
of SCD during 1st attack, but not later (Meisel et al 1991)
• Short coronary occlusions lead to preconditioning
and adaptation in experimental models
27. Genetic Factors?
• No direct evidence, but...
• Clinical and angiographic factors poor
predictors
• Genetic background in wide interindividual
variation in autonomic function (Singh et al Circulation
1999)
• Parental history of SCD (Jouven et al Circulation 1999)
28. How to Modify the Risk?
• Plaque
modification
• Beta blockade
• Exercise ( Billman et al
Circulation 1984,Burke et al JAMA
1999)
29. Conclusions
Plaque rupture is the major cause of sudden death
at population level
Autonomic mechanisms modify significantly
clinical outcome
Clinical outcome is largely unpredictable
Plaque modification is the best way to modify the
outcome
30. Occluded coronary artery
LAD (58%)
LCX (21%)
RCA (21%)
LAD (79%)
LCX (5%)
RCA (5%)
LAD (93%)
LCX (7%)
No VA
(N=219
Solitary VA
(N=19)
Complex VA
(N=14)
34. Can we modify HRV and is it
useful ?
Pikkujämsä et al
35. Low HRV
A marker of arrhythmic death
• Observational studies: (Farrell et al 1991, Bigger et al 1992,1993,
Algra et al 1993, Hartikainen et al 1996, Copie et al 1996, Bigger et al 1996)
Problem: Definition of sudden death
• Case control studies (Huikuri et al 1995, Perkiömäki et al 1997)
Problem: Matching, HRV measurement after the end
point
• HRV is altered before the onset of VF / VT in pts
with a history of MI (Valkama et al 1995, Huikuri et al 1996,
Shusterman et al 1998, Vybiral et al 1993)
36. HRV and sudden cardiac death
• Is the positive predictive accuracy enough for
clinical decisions ?
- SDNN ( Nordic ICD Pilot Study): 1/33 appropriate
shocks / 2 yr
• Depressed HRV identifies post-MI pts who might benefit
from AMIO (EMIAT substudy, Malik et al, JACC 2000)
- new nonlinear indices better (?)
