Myocardial Ischemia: An Underrated Cause of Sudden Cardiac Death?

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
4
(No Transcript)
5
Underlying Arrhythmias of SCD83 Are Ventricular
Tachyarrhythmias
Adapted from Bayés de Luna A. Am Heart J.
1989117151-159.
6
Underlying Causes of Fatal ArrhythmiasCoronary
Artery Disease is Most Common
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 IschemiaMultifactorial 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 slowessential 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 lt 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)
Wyse, et al. J Am Coll Cardiol 2001381718-1724
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 2.9 9.7 18.7 44.2 21.
6 15.8 18.7 13.7
p Value 0.004 lt 0.001 0.132 0.004 0.851 0.206
0.007 0.148 lt 0.001 lt 0.001 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 2001381718-1724
18
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
910
1092
364
546
728
0
182
Days
1067 187
508 82
No. at Risk Primary VT/VF Transient VT/VF
2013 278
1722 238
Wyse, et al. J Am Coll Cardiol 2001381718-1724
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, n83
Cumulative Survival
Q wave MI, n78
p NS
Ischemia w/o MI, n22
910
1092
364
546
728
0
182
Days
Wyse, et al. J Am Coll Cardiol 2001381718-1724
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 SCDDaoud 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 researchpresumed 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