Myocardial Ischemia: An Underrated Cause of Sudden Cardiac Death?William T. Abraham, MD, FACP, FACC, FAHA

Professor of Medicine, Physiology, and Cell BiologyChair of Excellence in Cardiovascular Medicine

Chief, Division of Cardiovascular MedicineDeputy Director, Davis Heart & Lung Research Institute

The Ohio State UniversityColumbus, 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

Adapted from Bayés de Luna A. Am Heart J. 1989;117:151-159.

Underlying Arrhythmias of SCD83% Are Ventricular Tachyarrhythmias

Bradycardia17%

VT62%

Primary VF8%

Torsades de Pointes13%

Adapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001.

80%Coronary Artery

Disease

15%Cardiomyopathy

5% Other*

Underlying Causes of Fatal Arrhythmias

Coronary Artery Disease is Most Common

*ion-channel abnormalities, valvular or congenital heart disease, other causes

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 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

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)

Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724

Ischemic events New MI Non-Q-wave Q-wave Transient ischemia, no MIOther or unknown*Electrolyte imbalanceAntiarrhythmic drug reaction

n

183161837822502718

%

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

Patients with Primary VT/VF versusVT/VF due to Transient/Correctable Cause

nAge (yrs)LVEFMenCADCardiomyoapthyPrior history VF VT Atrial fibrillation MI CHF Diabetes CABG/PTCA AAD

Primary

2,01363.4 ± 12.30.35 ± 0.15

76.6%74.9%3.1%

4.3%15.0%22.3%57.5%38.4%17.8%26.2%13.1%

TransientCorrectable Cause

27861.0 ± 12.70.41 ± 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< 0.0010.1320.0040.851

0.2060.0070.148

< 0.001< 0.0010.4060.0030.783

Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724

Transient Cause: Younger, Better EF with Less HF, Less MI …but with More CAD and Less Revascularization

Survival Curves of Primary VT/VF vs Transient/Correctable Cause for VT/VFAfter adjustment for differences in patient variables

0

100 –

90 –

80 –

70 –

60 –

50 –

Days

CumulativeSurvival

Primary VT/VF

Transient VT/VF

No. at Risk Primary VT/VF Transient VT/VF

p = 0.008

182 364 546 728 910 1092

2013278

1722238

1067187

50882

Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724

Survival Curves for Non Q wave MI, Q wave MI, and Ischemia Without MI

Patients with a transient/correctable cause for VT/VF

0

1.0 –

0.9 –

0.8 –

0.7 –

0.6 –

0.5 –

Days

CumulativeSurvival

Non Q wave MI, n=83

Ischemia w/o MI, n=22

182 364 546 728 910 1092

Q wave MI, n=78

Wyse, et al. J Am Coll Cardiol 2001;38:1718-1724

p = NS

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?

• 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 Natale et al 1994 J Cardiovasc Electrophysiol

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

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