Download Clinical and cellular markers of diabetic nephropathy

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순환기 내과 R3 서정호
Specific type of VT

Torsades de pointes
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

Polymorphic tachycardia with normal QT interval with
ischemic heart disease
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
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Polymorphic VT
Associated with QT prolongation (often >0.60sec)
Initiated by “R-on-T” VPC
Should not be consisidered Torsades
Class I or III agents
Abolition of ischemia, revascularization
Polymorphic VT initiated by short coupled VPC
during exercise or catecholamine state
Accelerated Idioventricular Rhythm
Torsade de Pointes





Twisting of the points
Polymorphic VT
기저선 위아래로 교대로 나타나는 다양한 폭을
가진 파형
보통 비지속적
대부분 QTc 간격 연장이 선행
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Antiarrhythmics
Macrolide
TCA
Hypokalemia, hypomagnesemia,
Ischemic heart disease, congenital long QTS
Torsade de Pointes


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
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Early afterdepolarization
M/c cause: congenital, severe bradycardia,
potassium depeletion,Medication (class
IA,IC,III)
IV magnesium
Temporary pacing
Isoproterenol
Lidocaine, mexiletine, phenytoin
Potassium channel opener
Torsades de Pointes-Treatment

Removing precipitating factor
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




Correcting metabolic abnormalities
Removing drugs that induce QT
prolongation
Electrolyte abnormality(hypokalemia,
hypomagnesemia)
Antiarrhythmic Drug(quinidine)
Phenothiazine , TCA, Liquid protein diet,
Intracranial event, bradyarrhythmia
Torsades de Pointes-Treatment

Removing precipitating factor



Correcting metabolic abnormalities
Removing drugs that induce QT prolongation
Drug induced torsades de pointes

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Atrial or ventricular overdrive pacing and Mg
Congenital long QT syndrome
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B-blocker
Phenytoin(shorten QT interval)
Cervicothoracic sympathectomy
ICD with dual chambered pacing capability and B
blocker
Contents
Normal QT interval
Long QT syndrome
Definition
Causes
Management
Drug induced long QT syndrome
심장의 전도계
ECG Measurements

ECG measures
electrical activity of
heart



P wave: atrial
depolarization
Q-R-S wave:
ventricular
depolarization
T wave: ventricular
repolarization
http://www.cbi.dongnocchi.it/glossary/TWave.html
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•
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•
•
•
•
P : 2.5mm * 0.12초
PR 간격 : 0.12 ~ 0.20초
QRS군 : 30mm * 0.06 ~ 0.10초
Q파 : R파의 25% 미만 * 0.04초 미만
ST 분절 : -0.5 ~ +2mm
T파 : 5 ~ 10mm이하
QT간격 : RR간격의 50%이하
남<0.42초, 여<0.43초
Normal QT interval
QT interval: 심실 근육의 전기적 활성도와 회복
시간 간의 간격
심박수에 역비례
Bazett’s formula
Hodges and coworkers: QTc= QT + 0.00175(심실
박동수 –60)
상한 범위는 0.46 sec
여성에서 약간 길고 나이가 들수록 증가
여러 유도 간 차이- 가장 긴 QT interval
QT prolongation
Age and Sex
Prolonged QTc
(sec)
Reference
Range (sec)
Children (< 15 y)
> .46
< .44
Adult Males
> .45
< .43
Adult Females
> .46
< .45
http://www.emedicine.com/med/topic1983.htm
LQT Syndrome (LQTS)



LQT syndrome is a genetic disease
One of several causes of cardiac
arrhythmias
ECG Characteristics:


Prolongation of the Q-T interval
Deformation of T wave/presence of U
wave
Action Potentials: Normal vs.
LQT1
http://www.cvrti.utah.edu/~macleod/bioen/be6460/notes/Channels-LQTS.pdf
LQT Syndrome: Types
LQTS Type
Chromosomal
Locus
Mutated Gene
Ion Current
Affected
LQT1
11p15.5
KVLQT1
IKs
LQT2
7q35-36
HERG
IKr
LQT3
3p21-24
SCN5A
INa
LQT4
4q25-27
?
?
LQT5
21q22.1-22.2
KCNE1
(heterozygotes)
IKs
LQT6
21q22.1-22.2
MiRP1
IKr
http://www.emedicine.com/med/topic1983.htm
Disease Statistics
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
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Affects 1 in about 3000-5000
individuals
Potassium channel mutations (KvLQT1
and HERG) estimated to cause 87% of
all LQT syndromes
LQT3 (SCN5A): approximately 8%
LQT5 (KCNE1/minK), LQT6 (MiRP1):
5%
Genetic Basis

Type 1 arises as a result of a genetic
mutation
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
Chromosome 11
KvLQT1 gene
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Encodes potassium channel α subunit
Mutation leads to loss of function of K+ channel
Delayed potassium rectifying current (IKs)
Inherited
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Dominantly
Recessively
Chromosome 11
11p15.5
http://ghr.nlm.nih.gov/chromosome=11
Cardiac myocyte repolarization

IK responsible for repolarization of cell
during action potential
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IKs helps keep action potential duration at
normal levels
Problems with channel  longer APD
(lengthened because of abnormal
repolarization)
Romano-Ward and JLN
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
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Associated with KvLQT1 gene
Related to LQT1
Romano-Ward: autosomal dominant
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Characterized by gradual hearing loss
Jervell-Lange-Nielsen (JLN):
autosomal recessive
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Characterized by congenital deafness
Cardiac related symptoms
Abnormal heartbeat
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Tachyarrhythmias – fast heart rate (>100 bpm)

Torsades de Pointes
Syncope (Fainting)
Cardiac arrest (heart failure)
Sudden death
Caution!
Arrhythmia can be induced by:

Stress/ Exercise
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Accelerated heart rate
Superposition of action potentials
Treatment

β-blockers (suppresses sympathetic
nervous system)
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ICD/Pacemakers (control heart rhythm)

Gene therapy ?
Cellular Structure
• Phospholipid
bilayer
• Impermeable
• Spanning
proteins
• Channels,
receptors and
pumps
Ion Pumps
 Na+/K+ ATPase, 3 Na+ out 2 K+ in
Ion Channels
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Macromolecular protein
tunnels
Highly selective to
particular ion
Respond to various
modifiers (voltage, time,
other ion concentrations)
Conformational changes
Act as switches to
energy created by
pumps
Resting Membrane Potential
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
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Intracellular K+, 140
mM/L, extracelluar 4
mM/L
Intracelluar Na+, 1015mM/L, extracelluar
140 mM/L
At rest K+ channel is
open, others closed
Receptors
Na+ channels
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Phase 0 in fast
response
(ventricular atrial
and Purkinje) tissue
Voltage and time
dependent
Class I agents
Ca2+ Channels
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
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T type (transient, tiny),
pacemaker
L type (long-lasting)
dominant depolarizing
current (phase 0) of SA
and AV node, plateau
(phase 2) of ventricle,
atrium
L type, target of Ca2+
channel blockers
K+ Channels


IKl – voltage dependent, generates RMP
IK – responsible for repolarization, 2
components, IKr (rapid), IKs (slow)
Cardiac Action Potential
Antiarrhythmics
Vaughn-Williams Classification
Class I – Na+ channel blockers
IA – Procainamide, Disopyramide, Quinidine
IB – Lidocaine, Mexiletine, Tocainide
IC – Flecainide, Propafenone
Class II – Beta-blockers
Class III – K+ channel blockers
Sotalol, Ibutilide, Amiodarone, Dofetilide
Class IV – Ca2+ channel blockers
Class I
Na+ channel Blockers
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Slow conduction (IC>IA>IB)
Useful for reentrant rhythms in Na+
dependent tissue
Depress automaticity
IC’s prolong refractoriness without
affecting APD
IA’s block several K+ channels, inc APD
Class I
Na+ Channel Blockers
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Proarrhythmia risk
slow conduction
prolong QT
IC’s increase
mortality in
ischemic CM
Contraindicated
Class I
Na+ Channel Blockers
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IA/IC, atrial fib/flutter or atrial tach with
normal LV/no ischemia
IB no significant effect on atrial tissue
Lidocaine indicated for VF/VT
Class II
Beta-Blockers
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Reversibly bind to
beta-receptors
Decrease pacemaker
current, increase
threshold (dec
automaticity)
Indirect inhibition of L
type Ca2+ channels
(slow conduction in
AVN)
Class II
Beta-Blockers
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Hyperadrenergic states
reduce SCD risk post MI, CHF
automatic rhythms (atrial tach)
Reentrant rhythms using AVN
AVRT, AVNRT
Slow ventricular rate in atrial fibrillation
No ventricular proarrhythmia
Bradycardia/heart block can limit use
Class III
K+ Channel Blockers
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Sotalol, Ibutilide,
Dofetilde inhibit IKr
Amiodarone inhibits
IKr and IKs
Markedly prolong
APD
Sotalol betablocker
Amio class I, II, IV
Class III
K+ Channel Blockers
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IKr blockers display reverse use
dependence
Torsade risk up to 8%!
Variant of LQTS
Amio no significant risk of ventricular
proarrhythmia
Possibly mediated by IKs block
Class III
K+ Channel Blockers
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IKr blockers, wide variety of reentrant
arrhythmias (afib, atrial flutter)
Avoided in presence of LVH and poor
LV function
Sotalol reduces ICD shocks
Amio broadest range of indications
Limited by bradycardia/AVN block and
extracardiac effects
Ca2+
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Class IV
Channel Blockers
Inhibit L type Ca2+ channels
Slow phase 4 (reduce automaticity) in SA and
AV nodes
Slow conduction/prolong refractoriness in AV
node
Useful for PSVT, slow ventricular rate in atrial
fibrillation, rare form of VT
Limited by bradycardia/AVN block
Mortality neutral, no ventricular proarrhythmia
Adenosine
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Endogenous nucleoside
Adenosine (A1) receptor agonist
Activates outward IKAdo K+ current
causing hyperpolarization
Inhibits pacemaker current
Results in profound slowing of
sinus rate, AV nodal block
Agent of choice for PSVT
Digoxin
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Inhibits Na+/K+
pump
Increases
intracellular Ca2+
Increases Vagal
tone
Atrial fibrillation in
presence of CHF
PSVT in pregnancy
Mortality neutral
Antiarrhythmics