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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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1/98 medslides.com 7

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



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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.

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