1. Myocardial Ischemia: An Underrated Cause of Sudden Cardiac Death?
William T. Abraham, MD, FACP, FACC, FAHA
Professor of Medicine, Physiology, and Cell Biology
Chair of Excellence in Cardiovascular Medicine
Chief, Division of Cardiovascular Medicine
Deputy Director, Davis Heart & Lung Research Institute
The Ohio State University
Columbus, Ohio

2. Disclosures
- Dr. Abraham has received research grants and/or consulting fees from Biotronik, Medtronic, and St. Jude Medical

3. Ohio State University Sudden Cardiac Death (SCD) Research Center

5. Underlying Arrhythmias of SCD 83% Are Ventricular Tachyarrhythmias
Bradycardia 17%
VT 62%
Primary VF 8%
Torsades de Pointes 13%
Adapted from Bayés de Luna A. Am Heart J ;117:

6. 80% Coronary Artery Disease
Underlying Causes of Fatal Arrhythmias Coronary Artery Disease is Most Common
80% Coronary Artery Disease
15% Cardiomyopathy
5% Other*
*ion-channel abnormalities, valvular or congenital heart disease, other causes
Adapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001.

7. Mechanisms of VT/VF in Acute Ischemia
Dispersion of refractoriness
Potassium current
Alteration of conduction velocity and propagation
Sodium current
Enhanced abnormal automaticity
Calcium current

8. Dispersion of Refractoriness
Alteration of potassium handling alters local action potential duration/refractoriness
Regional increase in interstitial concentration related to cell lysis
Accumulation of ADP in ischemic tissue directly alters cellular potassium current

9. Altered Conduction Velocity
Lack of mitochondrial function/ATP results in loss of sodium/calcium current
Slowed and differential conduction
Spontaneous multifocal ventricular ectopy
Abnormal automaticity related to altered calcium current

10. VT/VF in Acute Ischemia Multifactorial Mechanisms
Altered handling of sodium, potassium and calcium current
Dispersion of refractoriness/ areas of functional block
Differential conduction propagation/velocity
Multifocal automatic discharges
Promotes local reentry and prompt degeneration into PMVT/VF
Thus if a patient presents with monomorphic VT it rarely is related to acute ischemia

11. VT in Chronic Ischemic Heart Disease
Scar from Prior MI
Establishes a zone of slow conduction
Tissue within the infarct that is viable but not healthy
Conduction is slow…essential substrate to establish reentry
Random ventricular ectopy that otherwise would be benign becomes malignant in setting of scar and slow conduction
Reentry

12. ACC/AHA/HRS Guidelines: Indications for ICDs
Class III Indication: Ventricular tachyarrhythmias due to a transient or reversible disorder (e.g., acute MI, electrolyte imbalance, drugs, or trauma) when correction of the disorder is considered feasible and likely to substantially reduce the risk of recurrent arrhythmias. Level of evidence: B.

13. How Reversible Are Reversible Causes (e.g., Ischemia) of SCD?
In every ICD clinical trial:
Patients with sustained VT or VF due to an identifiable transient or correctable cause have been excluded
Presumption that these patients are at low risk for recurrent malignant ventricular arrhythmias, thus little benefit for ICD
No clinical trials to support this approach

14. AVID Trial: Amiodarone Versus ICD for Secondary Prevention VT/VF, EF < 40%
Registry of all patients screened
Excluded patients with transient or correctable cause of VT/VF
Wyse et al, JACC 2001: Assessed mortality of
patients screened but excluded from AVID due to correctable cause versus
patients enrolled in AVID for secondary prevention of VT/VF and who received an ICD

15. Transient/Reversible Causes
Determined by the AVID principal investigator at each site
Classified as
New Q-wave MI
New non Q-wave MI
Other ischemic event
Proarrhythmic drug reaction
Electrolyte imbalance (hypo-K/-Mg)
Other

16. Transient or Correctable Causes of VT/VF (n = 278)
Ischemic events
New MI
Non-Q-wave
Q-wave
Transient ischemia, no MI
Other or unknown*
Electrolyte imbalance
Antiarrhythmic drug reaction n
183
161 83 78 22 50 27 18 %
65.8%
57.9%
29.9%
28.0%
7.9%
17.9%
9.7%
6.5%
*Cocaine, or illicit drug use, sepsis, hypoxia, electrocution, drowning and other
Wyse, et al. J Am Coll Cardiol 2001;38:

17. Patients with Primary VT/VF versus
VT/VF due to Transient/Correctable Cause n
Age (yrs)
LVEF
Men
CAD
Cardiomyoapthy
Prior history VF VT
Atrial fibrillation MI
CHF
Diabetes
CABG/PTCA
AAD
Primary
2,013
63.4 ± 12.3
0.35 ± 0.15
76.6%
74.9%
3.1%
4.3%
15.0%
22.3%
57.5%
38.4%
17.8%
26.2%
13.1%
Transient
Correctable Cause
278
61.0 ± 12.7
0.41 ± 0.15
72.3%
82.0%
2.9%
9.7%
18.7%
44.2%
21.6%
15.8%
13.7%
p Value
0.004
< 0.001
0.132
0.851
0.206
0.007
0.148
0.406
0.003
0.783
Transient Cause: Younger, Better EF with Less HF, Less MI …but with More CAD and Less Revascularization
Wyse, et al. J Am Coll Cardiol 2001;38:

18. After adjustment for differences in patient variables
Survival Curves of Primary VT/VF vs Transient/Correctable Cause for VT/VF
After adjustment for differences in patient variables
100 –
90 –
80 –
70 –
60 –
50 –
Primary VT/VF
Cumulative
Survival
Transient VT/VF
p = 0.008
182
364
546
728
910
1092
Days
No. at Risk
Primary VT/VF
Transient VT/VF
2013
278
1722
238
1067
187
508 82
Wyse, et al. J Am Coll Cardiol 2001;38:

19. Survival Curves for Non Q wave MI, Q wave MI, and Ischemia Without MI
Patients with a transient/correctable cause for VT/VF
1.0 –
0.9 –
0.8 –
0.7 –
0.6 –
0.5 –
Non Q wave MI, n=83
Cumulative
Survival
Q wave MI, n=78
p = NS
Ischemia w/o MI, n=22
182
364
546
728
910
1092
Days
Wyse, et al. J Am Coll Cardiol 2001;38:

20. VT/VF in Setting of Acute Ischemia and Preserved EF (No Scar)
Often Exercise related
Considered low risk for recurrent VT/VF after successful management of ischemia
How many pts have only 1 Ischemic event?
Compliance with medical therapy
Reversibility of contributing features: DM, HTN, Hyperlipidemia
Few trials

21. VT/VF in Setting of Acute Ischemia and Depressed EF/Prior Scar due to Prior MI
Is VT/VF due to transient ischemia or due to scar-mediated VT or multifactorial?
Will revascularization prevent further episodes of SCD?
What is the impact of revascularization on scar?
Will revascularization manage a reentrant VT circuit?

22. Impact of CABG on SCD Natale et al 1994 J Cardiovasc Electrophysiol
Retrospective review of 58 pts with SCD and CABG with ICD placement
EP testing before and after CABG
Mean EF 31%; F/U of 4.6 years
22/58 (38%) with appropriate ICD therapies
EP testing was not predictive
Including post CABG EP testing

23. Impact of CABG on SCD Daoud et al, 1995 Am Heart J
23 pts survived SCD + noninducible at EP testing + ischemia on stress testing
CABG + ICD
Mean EF 28%; F/U 3.1 years
10/23 (43%) with ICD shocks
No clinical differences between pt with vs without ICD shocks
Conclusion: CABG not protective; no variables predicted ICD therapy

24. Conclusion: Transient (Acute) Ischemic Causes of VT/VF
Limited research…presumed not to be at increased risk for recurrent arrhythmias
It is sometimes difficult to ascertain with confidence that the VT/VF is reversible
Approach must be individualized for the patient and clinical scenario
Accomplish 3 goals:
Correctly identify all contributing features; and,
Fully correct the reversible cause(s); and,
High degree of confidence that reversible cause(s) will not recur