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Arrhythmia UpdateAnnabelle S. Volgman, MD FACC
Rush-Presbyterian-St. Lukes Medical Center
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Arrhythmia Update
Atrial Fibrillation
Supraventricular Tachycardias Ventricular Tachycardias and Sudden
Cardiac Death
Heart Failure Therapy
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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 Cardiol1997;20:381
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Atrial fibrillationaccounts for 1/3 of all
patient discharges
with arrhythmia asprincipal 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%
ConductionDisease
3% SCD
10% VT
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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 Med1995;155:469 Wolf PA et al. Stroke1991;22:983
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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 AF3
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
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Risk Factors for Stroke in AF
Risk Factor
Prior stroke
AgeHypertension
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 Med1994;154:1449
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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. Chest1995;108
Prystowsky EN et al. Circulation1996;1262
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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
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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 Electrophysiol1996;19:95
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Preference for Acute
Cardioversion
DC Cardioversion
i.v. Ibutilide
Other:
Oral Flecainide
Oral Propafenonei.v. Procainamide
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Preference for Acute Cardioversion
i .v. I buti l ide QTc460 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. Circulation1996; 94:1613-1621
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Preference for Acute Cardioversion
F lecainide / Propafenone / Procanimide
Indication for use not approved in the
United States
For oral agents
High single dose
Minimal structural heart disease
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Pharmacologic Cardioversion
Class Ia agentsprocainamide (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)
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Nonpharmacologic Alternatives
Radiofrequency ablationablation 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
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Atrial Fibrillation: Areas of
ResearchAFFIRM studyNational Heart Institutes atrial fibrillation study
Heart rate control and anticoagulation vs. rhythm control with
antiarrhythmic drugsPatient-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
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SPORTIF
Double-blind, randomized, multi-
center study to compare ximelagatran
to warfarin in patients with atrial
fibrillation
Ximelagatran, an oral thrombininhibitor that does not require
monitoring
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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
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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.
Di f At i l Fl tt Ci it Withi Ri ht
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Diagram of Atrial Flutter Circuit Within Right
Atrium
Cosio FG. Am J Cardiol. 1993;71:705-709.
Inferior vena cava -
tricuspid valve isthmus
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Ventricular Arrhythmias
From Palpitations
to Sudden Death
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Variability of Ventricular Ectopy
with Age
Effect of age on
probability (%) of
having more than agiven 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
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Sudden Death Syndrome
Incidence
400,000 - 500,000/year in U.S.
Only 2% - 15% reach the hospitalHalf of these die before discharge
High recurrence rate
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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.
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Clinical Substrates Associated with
VF Arrest
Coronary artery disease
Idiopathic cardiomyopathy
Hypertrophic cardiomyopathy
Long QT syndrome
RV dysplasia Rarely: WPW syndrome
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Risk Factors for Sudden Death in
Post-MI Patients
LVEF < 40%
Frequent ventricular ectopy
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Survival After Acute MI
Bigger JT. Am J Cardiol. 1986;57:12B.
3210
AB
CD
0.4
0.6
0.8
1.0
Survivo
rship
N536113
8037
EF 30% 30%
< 30%< 30%
VPD< 10/hr 10/hr
< 10/hr10/hr
0.2
A
B
C
D
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3020105210
(%)
Incidence (%/Year)
3002001000
(x 1000)
Total Events (#/Year)
Sudden Cardiac DeathIncidence and Total Events
Overall Incidencein Adult Population
Source: Myerburg RJ. Circulation. 1992;85(suppl I):I-2 I-10.
High CoronaryRisk Sub-Group
Any PriorCoronary Event
EF < 30%Heart Failure
Out-of-Hospital Cardiac Arrest
Survivors
Convalescent PhaseVT/VF After MI
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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
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Cardiac Electrophysiology Study
Invasive study to characterize electrical propertiesof heart including:
Sinus node dysfunction
AV nodal functionConduction abnormalitiesinfra-Hisian block
Accessory pathways of conduction
WPW
Mahaim
AV nodal reentry
Bundle branch reentry
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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 radiofrequencycatheter ablation
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Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5thed, 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 inpatients in functional NYHA Class II - IV
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Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5thed, 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
L QT S d
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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 potentiallylethal 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
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Evaluating Patients at Risk forSCA
Electrophysiologists (EPs) have madegreat 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
C i
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Small devices, pectoralimplant 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
DefibrillatorFirst-line therapy for patients at risk for SCA
1
Morgan Stanley Dean Witter. Investors Guide to ICDs. 2000.
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Atrium & VentricleVentricle
Therapies Provided by Todays
Dual-Chamber ICDs
Antitachycardia pacing
Cardioversion
Defibrillation
Bradycardia sensing
Bradycardia pacing
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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 incisionLateral thoracotomy
Procedure time 2 - 4 hours 1 hour
Perioperative 2.5% < 0.5%mortality
Post-implant 3 - 5 days 1 dayhospitalization
Battery longevity 18 months Up to 9 years
# Implants 0-2,000/yr 80,000/yr (E)1
1980s 200
0
Morgan Stanley D1ean Witter. Investors Guide to ICDs. 2000.
Evolution of ICD Therapy: 1980 to
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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 toPresent
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 TherapiesAVID
CASH
CIDS
1988 Tiered
Therapy
2000 Cardiac
Resynchro-
nization*
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Major Studies Confirm Efficacyof 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 ImplantationTrial (MADIT)
Multicenter Unsustained Tachycardia Trial
(MUSTT)
Reductions in Mortality with ICDs
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60%
MUSTT55 years
54%
MADIT42 years
20%
CIDS33 years
37%
CASH22 years
31%
AVID13 years
Reductions in Mortality with ICDs
Compared to Antiarrhythmic Drugs
0%
10%
20%
30%
40%
50%
60%
%M
ortalityRe
duction
1The AVID Investigators. N Engl J Med. 1997;337:1576-1583.
2Kuck K. ACC98 News Online. April, 1998. Press release.
3Connolly S. ACC98 News Online. April, 1998. Press release.4 Moss AJ. N Engl J Med. 1996;335:1933-1940.5Buxton AE. N Engl J Med. 1999;341:1882-1890.
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Source: Gregoratos G. J Am Coll Cardiol. 1998;31:1175-1209.
ACC/AHA Classifications ofProcedures and Treatments
Class I: Evidence/general agreement regarding
benefit, usefulness, and effectiveness
Class II: Conflicting evidence/divergence of
opinion regarding usefulness/effectivenessIIa: 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)
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Source: Gregoratos G. J Am Coll Cardiol. 1998;31:1175-1209.
1998 ACC/AHA Class I Indications
for ICD Therapy1. Cardiac arrest due to VF or VT not due to a transientor reversible cause
2. Spontaneous sustained VT
3. Syncope of undetermined origin with clinicallyrelevant, 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
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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.
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MADIT II
MADIT II Stopped Early: 30 PercentReduction 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 attacksurvivors receiving ICDs, compared with those taking
medications alone.
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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 bothstudy arms were taking Beta-blockers.
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Cardiac Resynchronization
Therapy for Heart Failure
Patient Selection
and Clinical Outcomes
Cardiac Resynchronization
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Cardiac Resynchronization
Therapy
Cardiac resynchronization, inassociation 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
A hi i C di R h i ti
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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
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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 InSyncSystem in patients
with moderate to severe heart failure (NYHAfunctional Class III/IV)
Abraham WT, et al. Journal of Cardiac Failure2000; Vol 6 No. 4.
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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 Failure2000; Vol 6 No. 4.
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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.
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Summary of On-going Trials
All cause mortality
or all causehospitalization
2200Randomized 1:2:2 to
OPT or OPT+CRT orOPT+CRT/ICD
(ICD always On)
COMPANION2
All cause mortality
or unplanned
cardiovascular
hospitalization
800Randomized 1:1to CRT + OPT or
OPT for 18 mos.
CARE-HF1
NYHA functional
Class,
6-min hall walk,
QoL
500+Randomized 1:1to CRT + OPT or
OPT for 6 mos.,
then all patients On
(ICD always On)
MIRACLE
ICD
PRIMARY
ENDPOINT
NUMBER
OFPATIENTS
DESIGNTRIAL
CRT = Cardiac Resynchronization Therapy, OPT = Optimal Pharmacologic Therapy
1Cleland JGF, et al. Eur J Heart Failure, 2001;3:481-489.2Bristow MR, Feldman AM, Saxon LA, et al. J Card Fail. 2000;6(no 3):276-285.Currently under clinical investigation in the United States.
I di ti f th M dt i I S
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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 heartfailure (NYHA Class III/IV)
QRS 130 ms
LV ejection fraction
35%
Implant Dissection/Perforation Events
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35296 (1.0)Total
12102 (0.3)Cardiac
vein/CS
Perforation
23194 (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*
S
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In Summary
Cardiac Resynchronization therapy
offers an adjunctive approach for
treating patients with ventriculardysynchrony in the setting of moderate
to severe heart failure who are on
optimal, stable medical therapy.