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From Vulnerable Plaque to Vulnerable Patient
Vulnerable (Arrhythmogenic)
Myocardium
K.E.J. Airaksinen
Turku, Finland
Sudden Death at Population Level
Role of Vulnerable Plaque
Occlusive Plaque rupture:
Sudden death, usually occurring within
minutes of the onset of chest pain, is the
first clinical...
Sudden Cardiac Death
General Adult (”Healthy”) Population
♦ Pathophysiology:
1) Coronary plaque rupture coronary occlusion...
”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 ...
Prevention of VF after Left Stellate
Ganglionectomy in Dogs
0
20
40
60
80
100 LSG
Control
20 min coronary occlusion
Puddu ...
PTCA-model to Simulate Coronary
Occlusion
2 min coronary occlusion
≈ 500 pts
♦ Beat-to-beat RRi and BP
♦ Ventricular arrhy...
Continuous ECG, Heart Rate and BP Recordings
RR interval
(ms)
Blood
pressure
(mmHg)
RR interval
(ms)
Blood
pressure
(mmHg)
HRV and Sudden Cardiac Death
Malignant ventricular arrhythmias caused
by abrupt coronary occlusion
are a major cause of su...
RR interval
(ms)
Blood
pressure
(mmHg)
HRV increase: Vagal Activation
RR interval
(ms)
Blood
pressure
(mmHg)
RR interval
(ms)
Blood
pressure
(mmHg)
HRV decrease: Vagal Withdrawal
-10
-5
0
5
10
15ChangeinRMSD(ms)
No VA Solitary VA Complex VA
p<0.01
p<0.05
Airaksinen et al Am J Cardiol 1999
HRV and Ven...
HRV Reactions and Ventricular
Arrhythmias
No VA Solitary VA Complex VA
16%
3%
26%
36%
No
RR
interval
(ms)
Blood
pressure
(mmHg)
RR interval
(ms)
Blood
pressure
(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 abrupt
coronary 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...
Gender Difference in Autonomic and
Hemodynamic Reactions
Reactions in women versus men
Adjusted OR (95% CI)
Bradycardia 3....
Is a Mild Stenosis More Hazardous??
♦SCD is the 1st symptom of CAD in 20-25%
♦Experimental models:
Coronary occlusion VF
T...
Stenosis Severity and the Occurrence of
Ventricular Ectopic Activity During Acute
Coronary Occlusion
0
10
20
30
VPBs(%)
*
...
Effect of Preocclusion Stenosis Severity on
Heart Rate Reactions to Coronary
Occlusion
26%
42%
32%
83%
17%
≤ 85% > 85%
Sev...
Adaptation Phenomena
• Psychological adaptation helpful in experimental
models (Parker et al 1987)
• Missile War or earthq...
RR interval
(ms)
Blood
pressure
(mmHg)
RR interval
(ms)
Blood
pressure
(mmHg)
Antiarrhythmic Effect of Repeated Coronary
O...
Genetic Factors?
• No direct evidence, but...
• Clinical and angiographic factors poor
predictors
• Genetic background in ...
How to Modify the Risk?
• Plaque
modification
• Beta blockade
• Exercise ( Billman et al
Circulation 1984,Burke et al JAMA...
Conclusions
Plaque rupture is the major cause of sudden death
at population level
Autonomic mechanisms modify significantl...
Occluded coronary artery
LAD (58%)
LCX (21%)
RCA (21%)
LAD (79%)
LCX (5%)
RCA (5%)
LAD (93%)
LCX (7%)
No VA
(N=219
Solitar...
Myocardial ischemia and repolarisation
ChangeinLnHFP
ChangeinLnRMSDChangeiNLnLFP
ChangeinLnHFPChangeinLnRMSDChangeinLnLFP
Effect of Beta Blockade on Heart Rate
V...
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 199...
HRV and sudden cardiac death
• Is the positive predictive accuracy enough for
clinical decisions ?
- SDNN ( Nordic ICD Pil...
RR interval
(ms)
Blood
pressure
(mmHg)
Increase in HRV during coronary occlusion
LF component - measure of sympathetic (or
vagal) tone ?
Increase in LF fluctuations
068 from vulnerable plaque to vulnerable patient
068 from vulnerable plaque to vulnerable patient
068 from vulnerable plaque to vulnerable patient
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068 from vulnerable plaque to vulnerable patient

  1. 1. From Vulnerable Plaque to Vulnerable Patient Vulnerable (Arrhythmogenic) Myocardium K.E.J. Airaksinen Turku, Finland
  2. 2. Sudden Death at Population Level Role of Vulnerable Plaque
  3. 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. 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. 5. ”Why do some people die when a coronary artery suddenly occludes ……and others develop only a myocardial infarction or UAP?”
  6. 6. Role of Autonomic Factors
  7. 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. 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. 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. 10. Continuous ECG, Heart Rate and BP Recordings RR interval (ms) Blood pressure (mmHg) RR interval (ms) Blood pressure (mmHg)
  11. 11. HRV and Sudden Cardiac Death Malignant ventricular arrhythmias caused by abrupt coronary occlusion are a major cause of sudden death
  12. 12. RR interval (ms) Blood pressure (mmHg) HRV increase: Vagal Activation
  13. 13. RR interval (ms) Blood pressure (mmHg) RR interval (ms) Blood pressure (mmHg) HRV decrease: Vagal Withdrawal
  14. 14. -10 -5 0 5 10 15ChangeinRMSD(ms) No VA Solitary VA Complex VA p<0.01 p<0.05 Airaksinen et al Am J Cardiol 1999 HRV and Ventricular Arrhythmias
  15. 15. HRV Reactions and Ventricular Arrhythmias No VA Solitary VA Complex VA 16% 3% 26% 36% No
  16. 16. RR interval (ms) Blood pressure (mmHg) RR interval (ms) Blood pressure (mmHg) Decrease in HRV before VT
  17. 17. Occlusion Strong Vasovagal Reactions may lead to Fatal Hypotension or Asystole during coronary occlusion BP 68/55
  18. 18. Arterial baroreflexes are impaired during abrupt coronary occlusion Airaksinen et al JACC 1998
  19. 19. Can We Predict the Risk of Sudden Death?
  20. 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. 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. 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. 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. 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. 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
  26. 26. RR interval (ms) Blood pressure (mmHg) RR interval (ms) Blood pressure (mmHg) Antiarrhythmic Effect of Repeated Coronary Occlusion Airaksinen & Huikuri, JACC 1997;29:1035-8 Similar effect on autonomic reactions 1st Occlusion 2nd Occlusion VPCs
  27. 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. 28. How to Modify the Risk? • Plaque modification • Beta blockade • Exercise ( Billman et al Circulation 1984,Burke et al JAMA 1999)
  29. 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. 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)
  31. 31. Myocardial ischemia and repolarisation
  32. 32. ChangeinLnHFP ChangeinLnRMSDChangeiNLnLFP ChangeinLnHFPChangeinLnRMSDChangeinLnLFP Effect of Beta Blockade on Heart Rate Variability During Vessel Occlusion at the Time of Coronary Angioplasty Airaksinen et al Am J Cardiol 1996
  33. 33. Can we modify HRV and is it useful ? Pikkujämsä et al
  34. 34. 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)
  35. 35. 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 (?)
  36. 36. RR interval (ms) Blood pressure (mmHg) Increase in HRV during coronary occlusion
  37. 37. LF component - measure of sympathetic (or vagal) tone ? Increase in LF fluctuations
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    Jul. 6, 2018

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