Transcript Ischemia and SCD

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
Disclosures
- Dr. Abraham has received research grants
and/or consulting fees from Biotronik,
Medtronic, and St. Jude Medical
Ohio State University Sudden Cardiac
Death (SCD) Research Center
Underlying Arrhythmias of SCD
83% Are Ventricular Tachyarrhythmias
Torsades de Pointes
13%
Bradycardia
17%
Primary VF
8%
VT
62%
Adapted from Bayés de Luna A. Am Heart J. 1989;117:151-159.
Underlying Causes of Fatal
Arrhythmias
Coronary Artery Disease is Most Common
5% Other*
80%
Coronary Artery
Disease
15%
Cardiomyopathy
*ion-channel abnormalities, valvular or congenital heart disease, other causes
Adapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001.
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
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
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
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
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
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.
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
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
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
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;38:1718-1724
Patients with Primary VT/VF versus
VT/VF due to Transient/Correctable Cause
Primary
n
2,013
Age (yrs)
63.4 ± 12.3
LVEF
0.35 ± 0.15
Men
76.6%
CAD
74.9%
Cardiomyoapthy
3.1%
Prior history
VF
4.3%
VT
15.0%
Atrial fibrillation 22.3%
MI
57.5%
CHF
38.4%
Diabetes
17.8%
CABG/PTCA
26.2%
AAD
13.1%
Transient
Correctable Cause p Value
278
61.0 ± 12.7
0.41 ± 0.15
72.3%
82.0%
2.9%
0.004
< 0.001
0.132
0.004
0.851
2.9%
9.7%
18.7%
44.2%
21.6%
15.8%
18.7%
13.7%
0.206
0.007
0.148
< 0.001
< 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 2001;38:1718-1724
Survival Curves of Primary VT/VF vs
Transient/Correctable Cause for VT/VF
After adjustment for differences in patient variables
100 –
Primary VT/VF
90 –
Cumulative
Survival
80 –
Transient VT/VF
70 –
60 –
p = 0.008
50 –
0
182
364
546
728
910
1092
Days
No. at Risk
Primary VT/VF
Transient VT/VF
2013
278
Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724
1722
238
1067
187
508
82
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 –
Non Q wave MI, n=83
0.9 –
Cumulative
Survival
0.8 –
Q wave MI, n=78
0.7 –
p = NS
Ischemia w/o MI, n=22
0.6 –
0.5 –
0
182
364
546
Days
Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724
728
910
1092
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
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?
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
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
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