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From Vulnerable Plaque to Vulnerable Patient
Vulnerable (Arrhythmogenic) Myocardium
K.E.J. AiraksinenTurku, Finland
Sudden Death at Population LevelRole of Vulnerable Plaque
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
Sudden Cardiac DeathGeneral Adult (”Healthy”) Population
Pathophysiology:1) Coronary plaque rupture coronary occlusion SCD2) Electrical or mechanical abnormality– WPW-syndrome– Long QT-syndrome– idiopatic VF, Brugada syndrome...– HOCM, ARVD, myocarditis...
”Why do some people die when a coronary artery suddenly occludes……and others develop only a myocardial infarction or UAP?”
Role of Autonomic Factors
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
Prevention of VF after Left Stellate Ganglionectomy in Dogs
0
20
40
60
80
100 LSG
Control
20 min coronary occlusionPuddu et al 1988
P=0.001Survival
%
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 -stimulation
Continuous ECG, Heart Rate and BP Recordings
RR interval(ms)
Bloodpressure(mmHg)
RR interval(ms)
Bloodpressure(mmHg)
HRV and Sudden Cardiac Death
Malignant ventricular arrhythmias caused by abrupt coronary occlusion are a major cause of sudden death
RR interval (ms)
Bloodpressure(mmHg)
HRV increase: Vagal Activation
RR interval(ms)
Bloodpressure(mmHg)
RR interval(ms)
Bloodpressure(mmHg)
HRV decrease: Vagal Withdrawal
-10
-5
0
5
10
15C
hang
e in
RM
SD (m
s)
No VA Solitary VA Complex VA
p<0.01
p<0.05
Airaksinen et al Am J Cardiol 1999
HRV and Ventricular Arrhythmias
HRV Reactions and Ventricular Arrhythmias
No VA Solitary VA Complex VA
16%
3%26%
36%
No
RR interval(ms)
Bloodpressure(mmHg)
RR interval(ms)
Bloodpressure(mmHg)
Decrease in HRV before VT
Occlusion
Strong Vasovagal Reactions may lead to Fatal Hypotension or Asystole during coronary occlusion
BP 68/55
Arterial baroreflexes are impaired during abruptcoronary occlusion Airaksinen et al JACC 1998
Can We Predict the Risk of Sudden Death?
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
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
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
Stenosis Severity and the Occurrence of Ventricular Ectopic Activity During Acute
Coronary Occlusion
0
10
20
30
VPB
s(%
)
*
< 75 75-89 90-99Stenosis severity (%)
Airaksinen et al Am J Cardiol 1995b
P<0.01
P<0.01
Effect of Preocclusion Stenosis Severity on Heart Rate Reactions to Coronary
Occlusion
26%42%
32%83%
17%
85% > 85%
Severity of stenosisAiraksinen et el Am J Cardiol 1994
Vagus Vagus
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
RR interval (ms)
Bloodpressure(mmHg)
RR interval (ms)
Blood pressure(mmHg)
Antiarrhythmic Effect of Repeated Coronary Occlusion
Airaksinen & Huikuri, JACC 1997;29:1035-8Similar effect on autonomicreactions
1st Occlusion
2nd Occlusion
VPCs
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)
How to Modify the Risk?
• Plaque modification
• Beta blockade• Exercise ( Billman et al
Circulation 1984,Burke et al JAMA 1999)
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
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)
Myocardial ischemia and repolarisation
Cha
nge
in L
nHFP
Cha
nge
in L
nRM
SD
Cha
nge
iN L
nLFP
Cha
nge
in L
nHFP
Cha
nge
in L
nRM
SD
Cha
nge
in L
nLFP
Effect of Beta Blockade on Heart Rate Variability During Vessel Occlusion at theTime of Coronary Angioplasty
Airaksinen et al Am J Cardiol 1996
Can we modify HRV and is it useful ?
Pikkujämsä et al
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)
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 (?)
RR interval (ms)
Bloodpressure(mmHg)
Increase in HRV during coronary occlusion
LF component - measure of sympathetic (or vagal) tone ?
Increase in LF fluctuations
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