Arrhythmia Update

Annabelle S. Volgman, MD FACC

Rush-Presbyterian-St. Lukes Medical Center

Arrhythmia Update
Atrial Fibrillation
Supraventricular Tachycardias
Ventricular Tachycardias and Sudden
Cardiac Death
Heart Failure Therapy


Classification of Atrial Fibrillation
The 3 Ps
Permanent - Conversion to sinus rhythm not
possible
Persistent - Capable of being converted to
sinus rhythm
Paroxysmal - Converts spontaneously to
sinus rhythm
Gallagher MM and Camm AJ Clin Cardiol 1997;20:381
Atrial fibrillation
accounts for 1/3 of all
patient discharges
with arrhythmia as
principal diagnosis.

2% VF
Data source: Baily D. J Am Coll Cardiol. 1992;19(3):41A.
34%
Atrial
Fibrillation
18%
Unspecified
6%
PSVT
6%
PVCs
4%
Atrial
Flutter
9%
SSS
8%
Conduction
Disease
3% SCD
10% VT
AF: Anticoagulation - General Points
AF most common significant rhythm disorder
Prevalence: 1.5%-3% of patients in their 60s
5%-7% of patients in their 70s
10% of patients in their 80s
AF most potent common risk factor for stroke
Relative risk = 5
Patients with AF can be stratified according to
risk of stroke
Feinberg WM e al. Arch Intern Med 1995;155:469 Wolf PA et al. Stroke1991;22:983
1/98 medslides.com 6
AF: Anticoagulation - General Points
Anticoagulation (INR 2.0 - 3.0) can reduce
risk of stroke by 2/3
1,2

Aspirin has little effect on risk of stroke due
to AF
3

1 Hylek EM and Singer DE. Arch Intern Med 1994;120:897
2 Hylek EM et al. New Engl J Med 1966;335:540
3 The Atrial Fibrillation Investigators. Arch Intern Med 1997;157:1237
1/98 medslides.com 7
Risk Factors for Stroke in AF
Risk Factor
Prior stroke
Age
Hypertension
Diabetes
Relative Risk (multivariate)
2.5
1.4 (per decade)
1.6
1.7
Absolute Risk
Age < 65 years and no risk factors, lone AF: 1%/yr.
All others: 3.5%-8+%/yr lowered to ~1.5%/yr by warfarin
The Atrial Fibrillation Investigators Arch Intern Med 1994;154:1449
Elective Cardioversion of AF
Anticoagulation
Cardioversion appears to raise risk of embolism
1%-5% emboli within hours to weeks
Anticoagulation well before and after greatly
reduces risk
Standard guideline for electrical or drug
cardioversion
INR 2 - 3 for 3 weeks before; and
INR 2 - 3 for 4 weeks after NSR
IF AF < 2 days duration, no anticoagulation
Laupacle A et al. Chest 1995;108
Prystowsky EN et al. Circulation 1996;1262
Adequate Rate Control
At office visits
Apical heart rate (sitting): 80 / min
On 24-hour Holter monitor
Goal: average hourly heart rate 80 /
min; no hour 100-100 / min
Exercise testing (if available)
Inadequate: 85% age-predicated
maximum heart rate in stage I (Bruce) or
3 min of exercise
Tachycardia - Induced Cardiomyopathy
Chronic tachycardia in otherwise structurally
normal heart sole cause of developing ventricular
dysfunction
Animal models: Pacing at 240 bpm x 3 weeks
low output CHF
Can follow any chronic cardiac tachyarrhythmia
Fenelon G et al. Pacing Clinical Electrophysiol 1996;19:95
Preference for Acute
Cardioversion
DC Cardioversion
i.v. Ibutilide
Other:
Oral Flecainide
Oral Propafenone
i.v. Procainamide
Preference for Acute Cardioversion
i.v. I butilide
QT
c
460 msec
Short duration of AF
No clinical CHF
Anesthesia risk (e.g., COPD)
Patient preference
Acute efficacy - flutter (63%), fib (31%)
Caution: risk of polymorphic VT (8%)
Stambler BS, et al. Circulation 1996; 94:1613-1621
Preference for Acute Cardioversion
Flecainide / Propafenone / Procanimide
Indication for use not approved in the
United States
For oral agents
High single dose
Minimal structural heart disease
Pharmacologic Cardioversion
Class Ia agents
procainamide (Procanbid)
quinidine (Quinidex, Quinaglute)
disopyramide (Norpace)
Class Ic agents
flecainide (Tambocor)
propafenone (Rhythmol)
Class III agents
amiodarone (Cordarone) - acute efficacy 16%-71%
sotalol (Betapace)
ibutilide - efficacy for flutter (63%), fib (31%)
dofetilide (Tikosyn)
Nonpharmacologic Alternatives
Radiofrequency ablation
ablation of the AV junction
ablation creating linear lesion in the atriums
ablation of foci around the pulmonary veins
Surgical approaches
the corridor procedure
isolating the sinus and AV nodes from the
remaining right and left atria
the maze procedure
dividing the left and right atria by multiple
surgical incisions
AFFIRM
Atrial Fibrillation Follow-up Investigation of
Rhythm Management
Hypothesis: Effect on mortality of antiarrhythmic
therapy to maintain sinus rhythm vs.
ventricular rate control alone, in the presence of
anticoagulation
Primary endpoint: Total mortality
Secondary endpoint: Disabling CVA
Cost of therapy
Quality of life
NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202.
Atrial Fibrillation: Areas of
Research
AFFIRM study
National Heart Institutes atrial fibrillation study
Heart rate control and anticoagulation vs. rhythm control with
antiarrhythmic drugs
Patient-activated or automatic atrial defibrillator
Dual-site and biatrial pacing
Atrial pacing therapies for AF prevention
Catheter ablation therapies for AF
Catheter maze procedure
Ablation for focal AF
SPORTIF
Double-blind, randomized, multi-
center study to compare ximelagatran
to warfarin in patients with atrial
fibrillation
Ximelagatran, an oral thrombin
inhibitor that does not require
monitoring
Supraventricular Tachycardias
AV nodal reentry tachycardia
AV reentry tachycardia - WPW Syndrome
Atrial flutter


If the patient is very symptomatic or breaks
through drugs, consider catheter ablation
RF Ablation of Atrial Flutter
Atrial flutter involves a macro-reentry circuit within the
right atrium and driving the left atrium.
Critical areas of conduction within the right atrium are
necessary to sustain atrial flutter.
RF ablation of conduction within such critical sites (most
commonly the inferior vena cava-tricuspid valve isthmus)
abolishes atrial flutter.
Cosio FG. Am J Cardiol. 1993;71:705-709.
Diagram of Atrial Flutter Circuit Within Right
Atrium
Cosio FG. Am J Cardiol. 1993;71:705-709.
Inferior vena cava -
tricuspid valve isthmus
Ventricular Arrhythmias
From Palpitations
to Sudden Death
Variability of Ventricular Ectopy
with Age
Effect of age on
probability (%) of
having more than a
given number of
PVCs per 24 hours
in subjects with
normal hearts.
0%
10%
20%
30%
40%
50%
60%
> 0 PVCs
> 50 PVCs
> 100 PVCs
10-29 30-39 40-49 50-59 60-69
Data from Kostis JB. Circulation.
1981;63(6):1353.
Age
Sudden Death Syndrome
Incidence
400,000 - 500,000/year in U.S.
Only 2% - 15% reach the hospital
Half of these die before discharge

High recurrence rate
Underlying Arrhythmia of
Sudden Death
VT
62%
Bradycardia
17%
Torsades
de Pointes
13%
Primary
VF
8%
Adapted from Bays de Luna A. Am Heart J. 1989;117:151-159.
Clinical Substrates Associated with
VF Arrest
Coronary artery disease
Idiopathic cardiomyopathy
Hypertrophic cardiomyopathy
Long QT syndrome
RV dysplasia
Rarely: WPW syndrome
Risk Factors for Sudden Death in
Post-MI Patients
LVEF < 40%
Frequent ventricular ectopy
Survival After Acute MI
Bigger JT. Am J Cardiol. 1986;57:12B.
3 2 1
0
A
B
C
D
0.4
0.6
0.8
1.0
S
u
r
v
i
v
o
r
s
h
i
p

N
536
113
80
37
EF
30%
30%
< 30%
< 30%
VPD
< 10/hr
10/hr
< 10/hr
10/hr
0.2
A
B
C
D
30 20 10 5 2 1 0
(%)
Incidence (%/Year)
300 200 100 0
(x 1000)
Total Events (#/Year)
Sudden Cardiac Death
Incidence and Total Events
Overall Incidence
in Adult Population
Source: Myerburg RJ. Circulation. 1992;85(suppl I):I-2 I-10.
High Coronary
Risk Sub-Group
Any Prior
Coronary Event
EF < 30%
Heart Failure
Out-of-Hospital Cardiac Arrest
Survivors
Convalescent Phase
VT/VF After MI
High-Risk Subgroups Who
Need Further Evaluation
Survivors of sudden death
Post-MI, reduced EF, and ventricular ectopy
Recurrent unexplained syncope
Idiopathic cardiomyopathy with syncope or VT
Hypertrophic cardiomyopathy with syncope or
VT
Right ventricular dysplasia
Long QT syndrome
Cardiac Electrophysiology Study
Invasive study to characterize electrical properties
of heart including:
Sinus node dysfunction
AV nodal function
Conduction abnormalities infra-Hisian block
Accessory pathways of conduction
WPW
Mahaim
AV nodal reentry
Bundle branch reentry
Cardiac Electrophysiology Study
Inducibility of VT
Reentrant (ischemic VT)
Triggered (idiopathic VT)
Assessment of antiarrhythmic therapy via
serial drug testing
May lead to therapy with radiofrequency
catheter ablation
Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5
th
ed, Vol 1.
Philadelphia: WB Saunders Co; 1997:ch 24.
Middlekauf HR. J Am Coll Cardiol. 1993;21:110-116.
Stevenson WE. Circulation. 1993;88:2953-2961.

Heart Failure
About one-half of all deaths in heart failure
patients are characterized as sudden due to
arrhythmias
The risk of SCA increases as left ventricular
function deteriorates (low LVEF)
Unexplained syncope has predicted SCA in
patients in functional NYHA Class II - IV
Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5
th
ed, Vol 1.
Philadelphia: WB Saunders Co; 1997:ch 24.
Maron BJ. New Engl J Med. 2000;342:365-373.
Hypertrophic Cardiomyopathy
Sudden cardiac death is the most common cause of
death in patients with HCM
Prevalence of HCM is about 0.2% of the general
population and about 10% of HCM patients are
considered to be at high risk of SCA
Recent study showed that over a ten year
period > 50% of high-risk patients would
experience SCA
HCM is the most common cause of SCA in athletes
under 35 years of age
Schwartz PJ. Curr Probl Cardiol. 1997;22:297-351.
Smith WM. Ann Intern Med. 1980;93:578-584.
Garson A Jr. Circulation. 1993;87:1866-1872.
Long QT Syndrome
Idiopathic LQTS is a congenital disorder that may
lead to unexplained syncope, seizures,
and SCA
Patients either remain asymptomatic or
are prone to symptomatic and potentially
lethal arrhythmias
A positive family history of LQTS or SCA is
present in 60% of LQTS patients
Due to the hereditary linkage, it is necessary to
identify other family members at risk
Evaluating Patients at Risk for
SCA
Electrophysiologists (EPs) have made
great strides in the last 15 years in the evaluation and
treatment of patients at risk for SCA
Electrophysiology Studies (EPS) have been helpful in
the diagnosis of cardiac arrhythmias including:
Sinus and AV node dysfunction
Conduction abnormalities
Accessory pathways of conduction
Inducibility of VT
EPs can provide advanced treatments including
Implantable Cardioverter Defibrillators (ICDs) and
ablation therapy
Small devices, pectoral
implant site
Transvenous, single incision
Local anesthesia; conscious sedation
Short hospital stays
Few complications
Perioperative mortality < 1%
Programmable therapy options
Single- or dual-chamber therapy
Battery longevity up to 9 years
80,000 implants/year (2000 E)
1
Implantable Cardioverter
Defibrillator
First-line therapy for patients at risk for SCA
1
Morgan Stanley Dean Witter. Investors Guide to ICDs. 2000.
Atrium & Ventricle Ventricle
Therapies Provided by Todays
Dual-Chamber ICDs
Antitachycardia pacing
Cardioversion
Defibrillation
Bradycardia sensing
Bradycardia pacing
Advances in ICD Implantation
Implanting Physician Cardiac surgeon EP or surgeon
Device size 120 - 140 cc < 40 cc
Implant Site Abdominal Pectoral
Procedure Median sternotomy Skin incision
Lateral thoracotomy
Procedure time 2 - 4 hours 1 hour
Perioperative 2.5% < 0.5%
mortality
Post-implant 3 - 5 days 1 day
hospitalization
Battery longevity 18 months Up to 9 years
# Implants 0-2,000/yr 80,000/yr (E)
1
1980s 200
0
Morgan Stanley D
1
ean Witter. Investors Guide to ICDs. 2000.
Number of Worldwide ICD Implants Per Year
* Under clinical investigation in the US
0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
80,000
90,000
100,000
1980 1985 1990 1995 2000 E
Evolution of ICD Therapy: 1980 to
Present
1980
First Human
Implant
1985
FDA Approval
of ICDs
1999
MUSTT
1993
Smaller
Devices
1996
Steroid
Leads
MADIT
1989
Transvenous
Leads
Biphasic
Waveform
1997/98
DC ICDs
AT Therapies
AVID
CASH
CIDS
1988
Tiered
Therapy
2000
Cardiac
Resynchro-
nization*
Major Studies Confirm Efficacy
of ICD over Antiarrhythmic Drug
Therapy
VT/VF patients:
Antiarrhymics Versus Implantable Defibrillators
(AVID)
Cardiac Arrest Study Hamburg (CASH)
Canadian Implantable Defibrillator Study (CIDS)
High-risk post-MI patients:
Multicenter Automatic Defibrillator Implantation
Trial (MADIT)
Multicenter Unsustained Tachycardia Trial
(MUSTT)
60%
MUSTT
5
5 years
54%
MADIT
4
2 years
20%
CIDS
3
3 years
37%
CASH
2
2 years
31%
AVID
1
3 years
Reductions in Mortality with ICDs
Compared to Antiarrhythmic Drugs
0%
10%
20%
30%
40%
50%
60%
%

M
o
r
t
a
l
i
t
y

R
e
d
u
c
t
i
o
n


1
The AVID Investigators. N Engl J Med. 1997;337:1576-1583.
2
Kuck K. ACC98 News Online. April, 1998. Press release.

3
Connolly S. ACC98 News Online. April, 1998. Press release.
4
Moss AJ. N Engl J Med. 1996;335:1933-1940.
5
Buxton AE. N Engl J Med. 1999;341:1882-1890.
Source: Gregoratos G. J Am Coll Cardiol. 1998;31:1175-1209.
ACC/AHA Classifications of
Procedures and Treatments
Class I: Evidence/general agreement regarding
benefit, usefulness, and effectiveness
Class II: Conflicting evidence/divergence of
opinion regarding usefulness/effectiveness
IIa: Weight of evidence/opinion in favor
of usefulness/effectiveness
IIb: Usefulness/effectiveness less well
established by evidence/opinion
Class III: Evidence/general agreement regarding
lack of usefulness/effectiveness
(harmful in some cases)
Source: Gregoratos G. J Am Coll Cardiol. 1998;31:1175-1209.
1998 ACC/AHA Class I Indications
for ICD Therapy
1. Cardiac arrest due to VF or VT not due to a transient
or reversible cause
2. Spontaneous sustained VT
3. Syncope of undetermined origin with clinically
relevant, hemodynamically significant sustained VT
or VF induced at EP study when drug therapy is
ineffective, not tolerated, or not preferred
4. Nonsustained VT with coronary disease, prior MI,
LV dysfunction, and inducible VF or sustained VT at
EP study that is not suppressible by a Class I
antiarrhythmic drug
MADIT II
A primary prevention trial comparing
outcomes with ICDs and conventional
treatment in heart attack survivors with
an ejection fraction of 30 percent or
lower.
MADIT II

MADIT II Stopped Early: 30 Percent
Reduction in Mortality Reported with
ICDs
November 20, 2001 - The investigative team for the Multi-
center Automatic Defibrillator Implantation Trial (MADIT
II) announced today that the Independent Data and Safety
Monitoring Board stopped the study prematurely due to
significantly improved total survival for heart attack
survivors receiving ICDs, compared with those taking
medications alone.
MADIT II
Unlike prior studies, MADIT II included patients
who had no demonstrable evidence of
arrhythmias, and no EP study was required to
Determine if VT could be induced in the patient
population.

Approximately 70 percent of Patients in both
study arms were taking Beta-blockers.

Cardiac Resynchronization
Therapy for Heart Failure

Patient Selection
and Clinical Outcomes
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 cardiac resynchronization
ECG depicting IVCD
Transvenous Approach
Standard pacing leads in RA and RV

Specially designed left heart lead placed in a left ventricular
cardiac vein via the coronary sinus

Achieving Cardiac Resynchronization
Mechanical Goal: Pace Right and Left Ventricles
Cardiac Resynchronization System
MIRACLE Study Purpose
To compare the effect of CRT versus
no CRT on Quality of Life and functional
capacity in patients with chronic heart failure
and ventricular dysynchrony
To assess the safety of CRT using the
Medtronic InSync

System in patients
with moderate to severe heart failure (NYHA
functional Class III/IV)
Abraham WT, et al. Journal of Cardiac Failure 2000; Vol 6 No. 4.
MIRACLE Study Population
Symptomatic patients with heart failure
18 years of age
NYHA Functional Class III or IV
QRS duration 130 msec
LVEF 35% by echocardiography
LVEDD 55 millimeters (echo measure)
Stable HF medical regimen for 1-month
ACE-I or substitute, if tolerated
-blocker - stable regimen for 3-months
Abraham WT, et al. Journal of Cardiac Failure 2000; Vol 6 No. 4.
MIRACLE Pivotal Phase
Conclusions
In NYHA Class III and IV heart failure patients with
intraventricular conduction delays who are on stable,
optimal medical therapy, cardiac resynchronization
therapy
is safe and well tolerated
improves quality of life, functional class, and
exercise capacity
improves cardiac structure and function
improves heart failure composite response
Abraham WT, et al. MIRACLE Trial Results; ACC 2001.
Summary of On-going Trials
All cause mortality
or all cause
hospitalization
2200
Randomized 1:2:2 to
OPT or OPT+CRT or
OPT+CRT/ICD
(ICD always On)
COMPANION
2

All cause mortality
or unplanned
cardiovascular
hospitalization
800
Randomized 1:1
to CRT + OPT or
OPT for 18 mos.
CARE-HF
1

NYHA functional
Class,
6-min hall walk,
QoL
500+
Randomized 1:1
to CRT + OPT or
OPT for 6 mos.,
then all patients On
(ICD always On)
MIRACLE
ICD

PRIMARY
ENDPOINT
NUMBER
OF
PATIENTS
DESIGN TRIAL
CRT = Cardiac Resynchronization Therapy, OPT = Optimal Pharmacologic Therapy
1
Cleland JGF, et al. Eur J Heart Failure, 2001;3:481-489.
2
Bristow MR, Feldman AM, Saxon LA, et al. J Card Fail. 2000;6(no 3):276-285.

Currently under clinical investigation in the United States.

Indications for the Medtronic InSync

Cardiac Resynchronization System
Medtronics InSync system is
indicated for the reduction of
symptoms in patients that meet
the following criteria:
Symptomatic despite stable,
optimal medical therapy
Moderate to severe heart
failure (NYHA Class III/IV)
QRS 130 ms
LV ejection fraction 35%

35 29 6 (1.0) Total
12 10 2 (0.3)
Cardiac
vein/CS
Perforation
23 19 4 (0.7)
CS
Dissection
Total
N
Observation
N
Complication
N ( %)
Event
All events were resolved without further sequelae.
*
Includes patient attempts from all study phases.
Implant Dissection/Perforation Events
579 Implant Procedures
*
In Summary
Cardiac Resynchronization therapy
offers an adjunctive approach for
treating patients with ventricular
dysynchrony in the setting of moderate
to severe heart failure who are on
optimal, stable medical therapy.