vulnerable patient symposium sca risk factors: what are the triggers?
TRANSCRIPT
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VULNERABLE PATIENT
SYMPOSIUMSCA Risk Factors:
What are the triggers?
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SOBERING STATS
• 30-50% SCD that are due to CAD occur as first cardiac event
• 1/3 SCD occur in pts with known CAD or risk markers but power insufficient to be useful marker
• Only a small % have well established risk markers (ICD trials)
• Therefore, >2/3 unable to predict
Zipes and Wellens Circ 1998; 98:2334; Myerburg JCE 2002; 13:709;
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PROBLEMS WITH RISK FACTORS
• LACK OF SPECIFICITY, SENSITIVITY, PREDICTIVE ACCURACY
• ABLE TO IDENTIFY POPULATIONS AT RISK BUT NOT INDIVIDUAL
• Present risk factors identify risk of developing SHD rather than proximate precipitator
• Need individual-specific predisposition: single patient probabilities, not population predictions
• Lack insight into mechanisms of SCD
Zipes and Wellens Circ 1998; 98:2334; Myerburg JCE 2002; 13:709;
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Risk Factors for SCA 1. Previous Sudden Cardiac Arrest Event
or Prior Episode of Ventricular Tachyarrhythmia (VT)
2. Decreased LVEF and heart failure3. Previous Myocardial Infarction
(MI)/Coronary Artery Disease (CAD)4. Ventricular Ectopy in Chronic
Ischemic Heart Disease; PVCs during recovery from TME
5. EP/ECG parameters: QTc. QRSd, HRV, BRS, EPS, TWA, SAECG, QT dispersion
6. Atrial fibrillation7. Smoking8. Obesity, DM9. Inactivity
10 Fatty acid metabolism: mitochondrial defects
11 Serum biomarkers: cytokines, other proteins
12 Inflammation: (CRP), troponin
13 Molecular markers: beta receptor subtypes
14 Genetics: control of substrate, thrombosis precipitators, inherited arrhythmias
15 Single nucleotide polymorphisms (SNPs): ion channels, other
16 Temperature17 Perfusion patterns: MRI18 Heart rate turbulence
STANDARD NEW
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26.7
22.1
15.815.6 16.915.3
9.8
13.8
0
5
10
15
20
25
30
1-17 mo 18-50 mo 51-121 mo > 121 mo
ConvICD
(n = 296) (n = 284) (n = 290) (n = 289)
Hazard Ratio 1.08
(p = 0.81)
0.56
(p < 0.001)
0.56
(p< 0.001)
0.56
(p < 0.001)
David J. Wilber MD, NASPE 2003. Abstract ID. 100865
Time Dependence of Mortality Risk Post-MI: MADIT-II
Time from MI
% M
ort
alit
y
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Time Dependence of Mortality Risk Post-MI
Maastricht Circulatory Arrest Registry:– In 224 SCA victims, only 4% were
due to an acute MI.
– The median time from MI to SCA was 9 years in 92 patients (41% of total).
Gorgels PMA. European Heart Journal. 2003;24:1204-1209.
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WHAT TRIGGERS SUDDEN CARDIAC DEATH?
“Why Did He Die On Tuesday and Not On Monday? Or On
Wednesday?”Adapted from an editorial (Zipes
DP Less heart is more. Circulation 107:2531, 2003) for a paper on
ventricular remodeling by Pfeffer and Braunwald
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ANATOMIC/FUNCTIONALANATOMIC/FUNCTIONALSUBSTRATESUBSTRATE
TRANSIENT INITIATINGTRANSIENT INITIATINGEVENTSEVENTS
ARRHYTHMIA MECHANISMSARRHYTHMIA MECHANISMS
Coronary artery diseaseCoronary artery diseaseCardiomyopathyCardiomyopathy
DilatedDilatedHypertrophicHypertrophic
Right ventricular dysplasiaRight ventricular dysplasiaValvularValvularCongenitalCongenitalPrimary electrophysiologicalPrimary electrophysiologicalNeurohumeralNeurohumeralDevelopmentalDevelopmentalInflammatory, infiltrative, Inflammatory, infiltrative,
neoplastic, degenerative, toxicneoplastic, degenerative, toxic
Neuro/endocrineNeuro/endocrineDrugsDrugsElectrolytes, pH, pO2Electrolytes, pH, pO2Ischemia/reperfusionIschemia/reperfusionHemodynamicHemodynamicStretchStretchArising/Stress/SleepArising/Stress/SleepALCOHOLALCOHOLEMDEMD
AsystoleAsystoleVTVTVFVF
ReentryReentryAutomaticityAutomaticityTriggered activityTriggered activityBlock/cell-to-cell uncouplingBlock/cell-to-cell uncoupling
Zipes and Wellens Circ 1998; 98:2334
Zipes, WellensSudden Cardiac DeathCirculation 1998
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40 yo man developed incessant SVT after second MI and development of RBBB
Prystowsky, Heger, Jackman, Naccarelli and Zipes AHJ 103:426-30, 1982
Spontaneous onset SVT
Rate 74 bpm Rate 81 bpm
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Atrial pre-excitation when His is refractory established
presence of a concealed accessory pathway
Early A
AHJ 103:426-30, 1982
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HV interval 50 ms: AP refractory
HV interval 90 ms post RBBB: AP conducts and SVT is initiated.
AHJ 103:426-30, 1982
81 bpm74 bpm
REMODELING REMODELING THAT ALTERSCONDUCTIONBY A FEW MSECCAN PRECIPITATETACHYCARDIAIN A SUBSTRATE PRESENT BUT DORMANT FOR YEARS
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WHY DO SOME PVCs INDUCE VT BUT OTHERS DO NOT?
EPICARDIUM IS MORE SENSITIVE TO THE EFFECTS OF ISCHEMIA THAN IS THE ENDOCARDIUM.
Transmural Reentry Triggered by Epicardial Stimulation during Acute Ischemia in Canine
Ventricular Muscle Wu J, Zipes DP
American Journal of Physiology
283: H2004-11, 2002
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OPTICAL MAPPING
Di-4-Anepps and cytochalasin D
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Asymmetrical conduction initiated by epi- & endocardial stimulation during acute ischemia
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“WINDOWS OF OPPORTUNITY DURING
ISCHEMIA”TIMING IS CRITICAL FOR DEVELOPMENT
OF REENTRANT VT v. NONE
EPICARDIAL v. ENDOCARDIAL PVCS
Heterogeneity precludes safe and effective pharmacotherapy but
supports benefits of ICDs
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Optical Mapping of the Functional Reentrant Circuit of
Ventricular Tachycardia in Acute Myocardial Infarction
Jianyi Wu, MD
Tamana Takahashi, MD
Pascal van Dessel, MD, PhD
William Groh, MD
John Miller, MD
Douglas P. Zipes, MD
SUBMITTED FOR PUBLICATION
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Therefore, timing and activation sequence determine whether or not VT/VF will occur after MI.
But, can ischemia predispose to VT/VF via other mechanisms?
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Prior ischemia enhances arrhythmogenicity in isolated
canine ventricular wedge model of Long QT 3
Norihiro Ueda, Douglas P. Zipes, Jiashin WuKrannert Institute of Cardiology, Indiana Univ. Sch. of
Medicine
IN PRESSCARDIOVASCULAR RESEARCH
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Conclusions
A prior episode of acute ischemia, even after apparent electrophysiologic recovery, enhances the arrhythmogenicity of ATX II (LQT3 model) through the development of EADs and reentry.
CAN ISCHEMA “SENSITIZE” PATIENTS WITH LQTS, OR OTHER DISEASE STATES, TO DEVELOPING SCD?
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TRIGGERS• MYOCARDIAL EP PROCESSES
PROBABLY DETERMINE ONSET/LACK OF VT/VF/SCD
• DIFFICULT TO MEASURE CLINICALLY; INDIRECT EP SURROGATES
• MUST CONTINUE TO RELY ON OTHER INDIRECT RISK FACTORS FOR NOW
• BUT MUST HAVE AED DEPLOYMENT FOR IMMEDIATE RESPONSE TO SAVE LIVES IN THE FORSEEABLE FUTURE