Presentation on theme: "Myocardial Ischemia: An Underrated Cause of Sudden Cardiac Death?"— Presentation transcript:
1Myocardial Ischemia: An Underrated Cause of Sudden Cardiac Death? William T. Abraham, MD, FACP, FACC, FAHAProfessor of Medicine, Physiology, and Cell BiologyChair of Excellence in Cardiovascular MedicineChief, Division of Cardiovascular MedicineDeputy Director, Davis Heart & Lung Research InstituteThe Ohio State UniversityColumbus, Ohio
2Disclosures- Dr. Abraham has received research grants and/or consulting fees from Biotronik, Medtronic, and St. Jude Medical
3Ohio State University Sudden Cardiac Death (SCD) Research Center
5Underlying 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:
680% Coronary Artery Disease Underlying Causes of Fatal Arrhythmias Coronary Artery Disease is Most Common80% Coronary Artery Disease15% Cardiomyopathy5% Other**ion-channel abnormalities, valvular or congenital heart disease, other causesAdapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001.
7Mechanisms of VT/VF in Acute Ischemia Dispersion of refractorinessPotassium currentAlteration of conduction velocity and propagationSodium currentEnhanced abnormal automaticityCalcium current
8Dispersion of Refractoriness Alteration of potassium handling alters local action potential duration/refractorinessRegional increase in interstitial concentration related to cell lysisAccumulation of ADP in ischemic tissue directly alters cellular potassium current
9Altered Conduction Velocity Lack of mitochondrial function/ATP results in loss of sodium/calcium currentSlowed and differential conductionSpontaneous multifocal ventricular ectopyAbnormal automaticity related to altered calcium current
10VT/VF in Acute Ischemia Multifactorial Mechanisms Altered handling of sodium, potassium and calcium currentDispersion of refractoriness/ areas of functional blockDifferential conduction propagation/velocityMultifocal automatic dischargesPromotes local reentry and prompt degeneration into PMVT/VFThus if a patient presents with monomorphic VT it rarely is related to acute ischemia
11VT in Chronic Ischemic Heart Disease Scar from Prior MIEstablishes a zone of slow conductionTissue within the infarct that is viable but not healthyConduction is slow…essential substrate to establish reentryRandom ventricular ectopy that otherwise would be benign becomes malignant in setting of scar and slow conductionReentry
12ACC/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.
13How 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 excludedPresumption that these patients are at low risk for recurrent malignant ventricular arrhythmias, thus little benefit for ICDNo clinical trials to support this approach
14AVID Trial: Amiodarone Versus ICD for Secondary Prevention VT/VF, EF < 40% Registry of all patients screenedExcluded patients with transient or correctable cause of VT/VFWyse et al, JACC 2001: Assessed mortality ofpatients screened but excluded from AVID due to correctable cause versuspatients enrolled in AVID for secondary prevention of VT/VF and who received an ICD
15Transient/Reversible Causes Determined by the AVID principal investigator at each siteClassified asNew Q-wave MINew non Q-wave MIOther ischemic eventProarrhythmic drug reactionElectrolyte imbalance (hypo-K/-Mg)Other
16Transient or Correctable Causes of VT/VF (n = 278) Ischemic eventsNew MINon-Q-waveQ-waveTransient ischemia, no MIOther or unknown*Electrolyte imbalanceAntiarrhythmic drug reactionn183161837822502718%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 otherWyse, et al. J Am Coll Cardiol 2001;38:
17Patients with Primary VT/VF versus VT/VF due to Transient/Correctable CausenAge (yrs)LVEFMenCADCardiomyoapthyPrior historyVFVTAtrial fibrillationMICHFDiabetesCABG/PTCAAADPrimary2,01363.4 ± 12.30.35 ± 0.1576.6%74.9%3.1%4.3%15.0%22.3%57.5%38.4%17.8%26.2%13.1%TransientCorrectable Cause27861.0 ± 12.70.41 ± 0.1572.3%82.0%2.9%9.7%18.7%44.2%21.6%15.8%13.7%p Value0.004< 0.0010.1320.8510.2060.0070.1480.4060.0030.783Transient Cause: Younger, Better EF with Less HF, Less MI …but with More CAD and Less RevascularizationWyse, et al. J Am Coll Cardiol 2001;38:
18After adjustment for differences in patient variables Survival Curves of Primary VT/VF vs Transient/Correctable Cause for VT/VFAfter adjustment for differences in patient variables100 –90 –80 –70 –60 –50 –Primary VT/VFCumulativeSurvivalTransient VT/VFp = 0.0081823645467289101092DaysNo. at RiskPrimary VT/VFTransient VT/VF20132781722238106718750882Wyse, et al. J Am Coll Cardiol 2001;38:
19Survival Curves for Non Q wave MI, Q wave MI, and Ischemia Without MI Patients with a transient/correctable cause for VT/VF1.0 –0.9 –0.8 –0.7 –0.6 –0.5 –Non Q wave MI, n=83CumulativeSurvivalQ wave MI, n=78p = NSIschemia w/o MI, n=221823645467289101092DaysWyse, et al. J Am Coll Cardiol 2001;38:
20VT/VF in Setting of Acute Ischemia and Preserved EF (No Scar) Often Exercise relatedConsidered low risk for recurrent VT/VF after successful management of ischemiaHow many pts have only 1 Ischemic event?Compliance with medical therapyReversibility of contributing features: DM, HTN, HyperlipidemiaFew trials
21VT/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?
22Impact of CABG on SCD Natale et al 1994 J Cardiovasc Electrophysiol Retrospective review of 58 pts with SCD and CABG with ICD placementEP testing before and after CABGMean EF 31%; F/U of 4.6 years22/58 (38%) with appropriate ICD therapiesEP testing was not predictiveIncluding post CABG EP testing
23Impact of CABG on SCD Daoud et al, 1995 Am Heart J 23 pts survived SCD + noninducible at EP testing + ischemia on stress testingCABG + ICDMean EF 28%; F/U 3.1 years10/23 (43%) with ICD shocksNo clinical differences between pt with vs without ICD shocksConclusion: CABG not protective; no variables predicted ICD therapy
24Conclusion: Transient (Acute) Ischemic Causes of VT/VF Limited research…presumed not to be at increased risk for recurrent arrhythmiasIt is sometimes difficult to ascertain with confidence that the VT/VF is reversibleApproach must be individualized for the patient and clinical scenarioAccomplish 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