Transcript Document

VULNERABLE
PATIENT
SYMPOSIUM
SCA Risk Factors:
What are the triggers?
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;
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;
Risk Factors for SCA
1.
2.
3.
4.
5.
6.
7.
8.
9.
Previous Sudden Cardiac Arrest Event
or Prior Episode of Ventricular
Tachyarrhythmia (VT)
Decreased LVEF and heart failure
Previous Myocardial Infarction
(MI)/Coronary Artery Disease (CAD)
Ventricular Ectopy in Chronic
Ischemic Heart Disease; PVCs during
recovery from TME
EP/ECG parameters: QTc. QRSd,
HRV, BRS, EPS, TWA, SAECG, QT
dispersion
Atrial fibrillation
Smoking
Obesity, DM
Inactivity
STANDARD
10
11
12
13
14
15
16
NEW 17
18
Fatty acid metabolism:
mitochondrial defects
Serum biomarkers:
cytokines, other proteins
Inflammation: (CRP),
troponin
Molecular markers: beta
receptor subtypes
Genetics: control of
substrate, thrombosis
precipitators, inherited
arrhythmias
Single nucleotide
polymorphisms (SNPs): ion
channels, other
Temperature
Perfusion patterns: MRI
Heart rate turbulence
Time Dependence of Mortality Risk
Post-MI: MADIT-II
30
Conv
ICD
26.7
25
22.1
% Mortality
20
15.6
15
15.8
15.3
13.8
16.9
9.8
10
5
0
1-17 mo
18-50 mo
51-121 mo
> 121 mo
Time from MI
(n = 296)
Hazard Ratio
1.08
(p = 0.81)
(n = 284)
0.56
(p < 0.001)
David J. Wilber MD, NASPE 2003. Abstract ID. 100865
(n = 290)
0.56
(p< 0.001)
(n = 289)
0.56
(p < 0.001)
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.
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
ANATOMIC/FUNCTIONAL
SUBSTRATE
TRANSIENT INITIATING
EVENTS
Coronary artery disease
Cardiomyopathy
Dilated
Hypertrophic
Right ventricular dysplasia
Valvular
Congenital
Primary electrophysiological EMD
Neurohumeral
Asystole
Developmental
VT
Inflammatory, infiltrative,
VF
neoplastic, degenerative, toxic
Zipes, Wellens
Sudden Cardiac Death
Zipes and Wellens
Circulation
1998 Circ 1998; 98:2334
Neuro/endocrine
Drugs
Electrolytes, pH, pO2
Ischemia/reperfusion
Hemodynamic
Stretch
Arising/Stress/Sleep
ALCOHOL
Reentry
Automaticity
Triggered activity
Block/cell-to-cell uncoupling
ARRHYTHMIA MECHANISMS
40 yo man developed incessant SVT after
second MI and development of RBBB
Rate 74 bpm
Rate 81 bpm
Spontaneous onset SVT
Prystowsky, Heger, Jackman, Naccarelli and Zipes AHJ 103:426-30, 1982
Atrial pre-excitation when His is refractory established
presence of a concealed
accessory pathway
Early A
AHJ 103:426-30, 1982
HV interval 50 ms: AP refractory
REMODELING
74 bpm
AHJ 103:426-30, 1982
81 bpm
HV interval 90 ms post RBBB:
AP conducts and SVT is initiated.
REMODELING
THAT ALTERS
CONDUCTION
BY A FEW MSEC
CAN PRECIPITATE
TACHYCARDIA
IN A SUBSTRATE
PRESENT BUT
DORMANT FOR
YEARS
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
OPTICAL MAPPING
Di-4-Anepps and cytochalasin D
Asymmetrical conduction initiated by epi- & endocardial
stimulation during acute ischemia
“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
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
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?
Prior ischemia enhances
arrhythmogenicity in isolated
canine ventricular wedge model of
Long QT 3
Norihiro Ueda, Douglas P. Zipes, Jiashin Wu
Krannert Institute of Cardiology, Indiana Univ. Sch. of
Medicine
IN PRESS
CARDIOVASCULAR RESEARCH
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?
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