Download KyungHee Univ. Hosp.

Arrhy-06
Cardiac Arrhythmias
과거와 현재
순환기내과
조 정휘
KyungHee Univ. Hosp.
Arrhy-06
The Past:
Birth of Cardiac Electrophysiology
 In the 1950s; intracardiac catheter to record
electrical activity and to stimulate the heart
 In the late 1960s; recording of the electrogram of His
bundle and electrical stimulation
 WPW syndrome; two connection exist between the
atrium and ventricle
 To initiate the tachycardia by programmed electrical
stimulation
KyungHee Univ. Hosp.
Arrhy-06
Development of cardiac EPS
 In the 1960s, recording of intracardiac electrical





activity at multiple locations
Programmed electrical stimulation at different
sites in the heart
PES resulted in the reproducible initiation and
termination of tachycardia
Localize the site of origin or pathway of the
different SVT
In the late 1960s, recording of the His bundle
electrograms; conduction over the AV node and
His bundle system
In the early 1970s, inducible VT
KyungHee Univ. Hosp.
Arrhy-06
Catheter Placement
KyungHee Univ. Hosp.
Arrhy-06
Arrhythmia Surgery
 Surgical therapy of WPW syndrome
 Ventricular tachycardia; surgical
excision of the area of abnormal
impulse formation
 In the 1980s, Maze operation for AF
KyungHee Univ. Hosp.
Arrhy-06
Cardiac Pacing
 Pacemaker; fixed rate ventricular pacing
 In the late of 1960s, antitachycardia pacing
 In the 1980s, implantable automatic
cardioverter-defibrillator
KyungHee Univ. Hosp.
Arrhy-06
Catheter Ablation
 The possibility of localizing the site of origin or
the pathway of a tachycardia; application of
ablative energy
 In the 1980s, high-energy shock; his bundle,
accessory pathway, AFL and VT
 Radio frequency energy
 One of the few curative treatment in cardiology
KyungHee Univ. Hosp.
Arrhy-06
Types of Energy Sources
 Direct current
 Radiofrequency
 Microwave
 Ultrasound
 Laser
 Chemical
 Cryogenic
 Surgical
KyungHee Univ. Hosp.
Arrhy-06
Temperature and Lesion Size
Blood
Tissue
Ablation catheter
Highest temperature reached
one millimeter below tissue surface
KyungHee Univ. Hosp.
Tissue
approx.
5 - 10 mm Ø
Arrhy-06
Schematic Diagram
of RF Current Delivery
Area of the myocardium that is
directly affected by the
current flow
Thermal injury by heat
conducted
from the zone of
resistive heating
Kalbfleish SJ, Langberg JJ.
KyungHee Univ. Hosp.
Arrhy-06
Ventricular Lesion
Following RF Ablation
KyungHee Univ. Hosp.
Arrhy-06
AVRT Left Free Wall Site
KyungHee Univ. Hosp.
Morady F. N Engl J of Med. 1999;340:534-544.
Arrhy-06
Antiarrhythmic drugs
 EPS guided serial drug therapy
 Prophylactic and empiric drug therapy
 The CAST; the possibility of proarrhythmic
effects of antiarrhythmic drugs (1989).
 The antiarrhythmic drugs may kill more
people than they save
KyungHee Univ. Hosp.
Arrhy-06
CAST-I
Prognosis of Post-MI Patients Treated with
Placebo vs. Encainide/Flecainide
Patients Without Event (%)
100
95
Placebo
(n = 743)
90
Encainide or
Flecainide (n = 755)
85
P = 0.001
80
0
91
182
273
364
455
Days After Randomization
KyungHee Univ. Hosp.
Echt DS. N. Engl J Med. 1991;324:781-788.
Arrhy-06
Proportion event-free
SWORD Survival Results
Study stopped prematurely
in Nov. 1994 due to
increased mortality in
patient population treated
with d-sotalol
1.00
.99
.98
.97
.96
.95
.94
.93
.92
.91
.90
.89
.88
.87
Placebo
dsotalol
Z = -2.5, P = 0.006
0
120
180
240
300
Time from randomization (days)
Patients at risk
Placebo
d-sotalol
60
1572
1549
KyungHee Univ. Hosp.
1170
1150
874
844
Waldo AL. Lancet. 1996;348:7-12.
551
544
330
323
Arrhy-06
Antiarrhythmic Drugs Post MI
Class IA
Class IB
1.19
1.06
Class IC (CAST)
2.38
-blockers
.81
Calcium Channel Blockers
Amiodarone (EMIAT)
DIAMOND MI
.96
.91
0.1
Julian et al. Lancet. 1997;349:667-674; Teo et al. JAMA. 1993;
270:1589-1595; Echt et al. N Engl J Med. 1991;324:781-788.
KyungHee Univ. Hosp.
1.04
1.0
Mortality Hazard Ratio
5.0 10.0
Arrhy-06
KyungHee Univ. Hosp.
Arrhy-06
The Present
 Sudden cardiac death
 Congestive heart failure
 Atrial fibrillation
KyungHee Univ. Hosp.
Arrhy-06
Coronary Heart Disease
 An estimated 13 million people had CHD in the U.S. in 2002. 1
 Sudden death was the first manifestation of coronary heart
disease in 50% of men and 63% of women. 1
 CHD accounts for at least 80% of sudden cardiac deaths in
Western cultures.3
Etiology of Sudden Cardiac Death2,3
5% Other*
15%
Cardiomyopathy
1
American Heart Association. Heart Disease and Stroke Statistics—2003 Update. Dallas, Tex.:
American Heart Association; 2002.
2
Adapted from Heikki et al. N Engl J Med, Vol. 345, No. 20, 2001.
3
Myerberg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 6th ed. P. 895.
KyungHee Univ. Hosp.
80%
Coronary
Heart
Disease
* ion-channel abnormalities, valvular or
congenital heart disease, other causes
Arrhy-06
Arrhythmic Cause of SCD
12%
Other Cardiac
Cause
88%
Arrhythmic
Cause
KyungHee Univ. Hosp.
.
Albert CM. Circulation. 2003;107:2096-2101
Arrhy-06
Underlying Arrhythmias of
Sudden Cardiac Arrest
Torsades de Pointes
13%
Bradycardia
17%
VT
62%
KyungHee Univ. Hosp.
Primary VF
8%
Bayés de Luna A. Am Heart J. 1989;117:151-159.
Arrhy-06
Risk Factors for SCD
 Previous Myocardial Infarction (MI)
 Decreased Left Ventricular Ejection Fraction






(LVEF)
Heart Failure
Previous Sudden Cardiac Arrest Event
Prior Episode of VT
Coronary Artery Disease (CAD)
Hypertrophic Cardiomyopathy (HCM)
Long QT Syndrome
KyungHee Univ. Hosp.
Arrhy-06
Risk-stratification for SCD
 Only 10% of SCD victims have a highrisk profile
 A low positive predictive accuracy
 Look for a better way to select
patients that should receive an ICD
for the primary prevention of SCD
KyungHee Univ. Hosp.
Arrhy-06
Survival Free of Cardiac Death
1.0
Cumulative Survival
.8
.6
Assigned Therapy
.4
Log rank p = 0.0042
Device
.2
0.0
0
KyungHee Univ. Hosp.
Drug
6 12 18 24 30 36 42 48
Months from Randomization
The AVID Investigators. JACC 1999; 34:1552-1559.
Arrhy-06
Meta-analysis of AVID/CASH/CIDS
Trial Cumulative Risk of Fatal Events
Death
60
60
50
50
Amiodarone
40
%
Arrhythmic death
40
30
%
20
0
0
1
2
3
4
Years
Connolly et al. Eur Heart J 2000;21:2071-8.
KyungHee Univ. Hosp.
Amiodarone
20
ICD
10
30
10
5
6
ICD
0
0
1
2
3
Years
4
5
6
Arrhy-06
Meta-analysis of AVID/CASH/CIDS
Trial Cumulative Risk of Fatal Events
LVEF 35%
LVEF >35%
%
60
60
50
50
40
40
Amiodarone
30
% 30
20
20
10
10
0
ICD
0
1
2
3
0
4
Years
Connolly et al. Eur Heart J 2000;21:2071-8.
KyungHee Univ. Hosp.
5
6
Amiodarone
ICD
0
1
2
3
Years
4
5
6
Arrhy-06
ICD Evolution
1970
•Patent granted for first
totally implantable
defibrillator
•System used an intracardiac
catheter and SQ patch with
detection via RV pressure
transducer
Michael Mirowski (1924-1990)
KyungHee Univ. Hosp.
Arrhy-06
ICD Evolution
KyungHee Univ. Hosp.
Arrhy-06
ICD Evolution
KyungHee Univ. Hosp.
Arrhy-06
Benefits of Tiered Therapy
VT
FVT
VF
KyungHee Univ. Hosp.
Arrhy-06
Examples of Success (A) and Failure (B)
A.
VT onset
ATP onset
Episode duration = 5.3 s
B.
1st ATP onset
VT onset
..
2nd ATP onset
KyungHee Univ. Hosp.
Accelerated VT
4.8 J shock
Episode duration = 16.8 s
Wathen M, Sweeney M, DeGroot P. Circulation. 2001; 104: 796-801.
Arrhy-06
Evolution of ICD Therapy: 1980 to Present
1980
1985
1993
1996
1999
• First Human
Implant
• FDA Approval
of ICDs
• Smaller
Devices
• Steroid
Leads
• MADIT
• MUSTT
• AT Therapies
100,000
90,000
1989
• Transvenous
Leads
• Biphasic
Waveform
80,000
70,000
60,000
50,000
1988
1997/98
• Tiered
Therapy
• DC ICDs
• Size
Reduction
• AVID
• CASH
• CIDS
40,000
30,000
20,000
10,000
0
1980
1985
KyungHee Univ. Hosp.
1990
1995
2000 E
Number of Worldwide ICD Implants Per Year
Arrhy-06
Incidence of SCD in Specific Populations
and Annual SCD Numbers
General adult
population
Multiple risk
subgroups
Patients with any
previous coronary
event
Patients with ejection
fraction <35% or CHF
SCD-HeFT
Cardiac arrest, VT/VF
survivors
AVID, CASH, CIDS
MADIT, MUSTT, MADIT II
High-risk post-MI
subgroups
0
5
10
20
25
30
Incidence of Sudden Death
(% of group)
KyungHee Univ. Hosp.
0
100,000 200,000 300,000
Incidence of Sudden
Deaths Per Year
(number)
Adapted from: Myerburg RJ. Sudden Cardiac Death: Exploring the Limits of Our Knowledge.
J Cardiovasc Electrophysiol Vol. 12, pp. 369-381, March 2001.
Arrhy-06
ICD Clinical Trials in Post-MI Patients
MADIT
Multicenter Automatic Defibrillator Implantation Trial
Moss AJ. N Engl J Med 1996:335:1933-40.
MUSTT
Multicenter Unsustained Tachycardia Trial
Buxton AE. N Engl J Med. 1999;341:1882-90.
MADIT-II
Multicenter Automatic Defibrillator Implantation Trial-II
Moss AJ. N Engl J Med. 2002;346:877-83.
KyungHee Univ. Hosp.
Arrhy-06
MADIT/MUSTT/MADIT-II
Patient Inclusion
Criteria
MADIT1
MUSTT2
MADITII3
X
X
X
X
(<35%)
X
(<40%)
X
(<30%)
NSVT
X
Inducible VT on EPS
X
X
X
Inducible, non-suppressible
VT on EPS
X
CAD/Post-MI
Low LVEF
1 Moss
KyungHee Univ. Hosp.
AJ. N Engl J Med. 1996;335:1933-40.
AE. N Engl J Med. 1999;341:1882-90.
3 Moss AJ. N Engl J Med. 2002; 346:877-83.
2 Buxton
Arrhy-06
MADIT Survival Results
Probability of survival
1.0
0.8
Defibrillator
0.6
Conventional
therapy
0.4
0.2
P-value = 0.009
0.0
0
1
2
3
4
5
95
80
53
31
17
3
101
67
48
29
17
0
No. of patients
Defibrillator
Conventional
therapy
KyungHee Univ. Hosp.
Year
Moss AJ. N Engl J Med. 1996;335:1933-40.
Arrhy-06
MUSTT Randomized Patient Results:
Total Mortality
0.6
EP-Guided Without
Defibrillator
0.5
No Antiarrhythmic
Therapy
Event Rate
0.4
0.3
p < 0.001
EP-Guided Therapy
with Defibrillator
0.2
0.1
0
0
KyungHee Univ. Hosp.
1
2
3
Time after Enrollment (Years)
Buxton AE. N Engl J Med. 1999;341:1882-90.
4
5
Arrhy-06
MADIT-II Survival Results
1.0
Probability of
Survival
0.9
Defibrillator
0.8
0.7
Conventional
P = 0.007
0.6
0.0
0
No. At Risk
Defibrillator 742
Conventional 490
KyungHee Univ. Hosp.
1
2
3
4
110 (0.78)
65 (0.69)
9
3
Year
502 (0.91)
329 (0.90)
274 (0.94)
170 (0.78)
Moss AJ. N Engl J Med. 2002;346:877-83.
Arrhy-06
Primary Prevention Post-MI Trials:
Reduction in Mortality with ICD Therapy
ICD
% Mortality
60
55%
Conventional
48%
No Rx
39%
40
27%
24%
24%
20
20%
16%
14%
0
CABG Patch
1
MADIT
27 Months
32 Months
1 Bigger
MUSTT
3
39 Months
JT. N Engl J Med. 1997;337(22):1569-1575.
Moss AJ. N Engl J Med. 1996;335:1933-40.
3 Buxton AE. N Engl J Med. 1999;341:1882-90.
4 Moss AJ. N Engl J Med. 2002;346:877-83.
5 Moss AJ. Presented before ACC 51st Annual Scientific Sessions,
Late Breaking Clinical Trials, March 19, 2002.
2
KyungHee Univ. Hosp.
2
MADIT-II
4,5
20 Months
Reductions in Mortality
with ICD Therapy
% Mortality Reduction w/ ICD Rx
Arrhy-06
75%
80
60
76%
Overall Death
Arrhythmic Death
61%
55%
54%
40
31%
20
ICD mortality reductions in
primary prevention trials
are equal to or greater
than those in secondary
prevention trials.
0
MADIT
1
% Mortality Reduction w/ ICD Rx
27 months
MUSTT
2
39 months
MADIT-II
3, 4
20 months
80
59%
60
Overall Death
Arrhythmic Death
56%
40
31%
33%
28%
20%
20
1
Moss AJ. N Engl J Med. 1996;335:1933-40.
Buxton AE. N Engl J Med. 1999;341:1882-90.
3 Moss AJ. N Engl J Med. 2002;346:877-83
4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions,
Late Breaking Clinical Trials, March 19, 2002.
5 The AVID Investigators. N Engl J Med. 1997;337:1576-83.
6 Kuck K. Circ. 2000;102:748-54.
7 Connolly S. Circ. 2000:101:1297-1302.
2
0
AVID 5
3 Years
KyungHee Univ. Hosp.
CASH 6
3 Years
CIDS 7
3 Years
Arrhy-06
Congestive Heart Failure
 Arrhythmic death as a common
mode of death in CHF occurring in
approximately half of the cases
 ICD improve the survival rate
KyungHee Univ. Hosp.
Arrhy-06
Cardiac Resynchronization Therapy
(CRT)
 Complete LBBB; different
patterns of LV contraction and
degree of mitral incompetence.
 Biventricular pacing to restore
resynchronization of ventricular
contraction
KyungHee Univ. Hosp.
Arrhy-06
Ventricular Dysynchrony
 Abnormal ventricular conduction resulting in a
mechanical delay
 Wide QRS (IVCD); typically LBBB morphology
 Poor systolic function
 Impaired diastolic function
ECG depicting interventricular conduction delay
KyungHee Univ. Hosp.
Arrhy-06
Cardiac Resynchronization Therapy
 Cardiac
resynchronization, in
association with an
optimized AV delay,
improves hemodynamic
performance by forcing
the left ventricle to
complete contraction and
begin relaxation earlier,
allowing an increase in
ventricular filling time.
 Coordinate activation of
the ventricles and septum.
ECG depicting IVCD
ECG depicting cardiac resynchronization
KyungHee Univ. Hosp.
Arrhy-06
Cardiac Venous Anatomy
and Lead Placement
2
5
KyungHee Univ. Hosp.
4
3 1
1. Lateral (marginal)
cardiac vein
2. Great cardiac vein
3. Postero-lateral cardiac
vein
4. Posterior cardiac vein
5. Middle cardiac vein
Arrhy-06
Final Lead Position
KyungHee Univ. Hosp.
Click to Start/Stop
Arrhy-06
MIRACLE Pivotal Phase
CRT Improves 6-Minute Hall Walk Distance
P=0.032
P=0.004
P=0.033
Meters
350
Control
N=116
CRT
N=121
300
250
Base1
line
Month
KyungHee Univ. Hosp.
3
Months
6
Months
Abraham WT, et al. MIRACLE Trial Results; ACC 2001.
Arrhy-06
MIRACLE Pivotal Phase
CRT Improves Quality of Life
Improvement
Total Score
30
P=0.020
P=0.051
P=0.013
1 Month
3 Months
6 Months
40
50
60
70
Baseline
Control N=114
CRT N=121
KyungHee Univ. Hosp.
Abraham WT, et al. MIRACLE Trial Results; ACC 2001.
Arrhy-06
MIRACLE Pivotal Phase
CRT Improves NYHA Class
P < 0.001
100%
13%
27%
80%
60%
90%
93%
40%
52%
Class
I
II
III
IV
64%
20%
32%
0%
Baseline 6-Months
Baseline 6-Months
Control (N = 117)
CRT(N = 124)
KyungHee Univ. Hosp.
Abraham WT, et al. MIRACLE Trial Results; ACC 2001.
Chi-square test
Arrhy-06
Atrial Fibrillation Demographics by Age
Feinberg WM, Blackshear JL, Laupacis A. Arch Intern Med. 1995;155:469-473
KyungHee Univ. Hosp.
Arrhy-06
Percent of AF Patients in
Sinus Rhythm Post-Cardioversion1
1
Dittrich HC, Erickson JS, Schneiderman T, et al. Am J Cardiol. 1989;63:193-197
KyungHee Univ. Hosp.
Arrhy-06
AFFIRM Study Protocol
Randomize
Heart rate control
anticoagulation
STEP I
Antithrombotic therapy per guidelines
Follow-up
> 2 pharmacologic trials
Antithrombotic therapy per guidelines
Cardioversion prn
Follow-up
> 2 pharmacologic trials
STEP I failure
or intolerance
Protocol-specified innovative
therapy for heart rate control,
or continue step I
pharmacologic trials
STEP I failure
or intolerance
STEP II
Antithrombotic therapy per guidelines
Follow-up
NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202.
KyungHee Univ. Hosp.
Maintain sinus rhythm
anticoagulation
Protocol-specified innovative therapy
for maintenance of sinus rhythm,
or continue step I pharmacologic
trials and prn cardioversion
Antithrombotic therapy per guidelines
Cardioversion prn
Follow-up
Arrhy-06
KyungHee Univ. Hosp.
Arrhy-06
Rate versus Rhythm Control
 Convert the AF by pharmacologic or
electrical cardioversion, and then keep in
sinus rhythm by antiarrhythmic drug
therapy
 The relative in efficiency of antiarrhythmic
drug therapy, side effects
 Rate versus rhythm control of AF(5,239)
 All cause mortality
– Rate control; 13%(339/2609)
– Rhythm control; 14.6%(382/2630)
– No significant difference in stroke incidence
KyungHee Univ. Hosp.
Arrhy-06
Atrial Fibrillation
 AF in the last big hurdle in treating SVT
 Ectopic impulse formation in and around
the pulmonary veins plays an important
role in the initiation and maintenance of
paroxysmal AF
 PV isolation with atrial ablation lines
 Only a minority of AF patients cane be
helps by catheter ablation
KyungHee Univ. Hosp.
Arrhy-06
MAZE
KyungHee Univ. Hosp.
Arrhy-06
KyungHee Univ. Hosp.
Arrhy-06
AT/AF Management Success
Drugs
Chemical
Cardioversion
20
30
40
Electrical
Cardioversion
50
60
70
80
% Success
100%
Flutter
Ablation
Linear Ablation
Focal AT Ablation
PV Quadrant/
Total Isolation
KyungHee Univ. Hosp.
90
Arrhy-06
Genetics







Long QT syndrome
Short QT syndrome
Brugada syndrome
Catecholaminergic polymorphic VT
Familial AF, Heart block
Arrhythmogenic RV cardiomyopathy
WPW syndrome
KyungHee Univ. Hosp.
Arrhy-06
The Future
 Device therapy; ICD
 New antiarrhythmic drug
 Stem cell therapy
 Genetic analysis; improve diagnostic
abilities and preventive measures
KyungHee Univ. Hosp.