Cardiac Resynchronization Cardiac Resynchronization Therapy: Therapy:

An Evolving New Therapy for An Evolving New Therapy for Heart Failure Heart Failure

HF Incidence and PrevalenceHF Incidence and Prevalence

•• Prevalence Prevalence –– Worldwide, 22 millionWorldwide, 22 million11

–– United States, 5 millionUnited States, 5 million22

•• Incidence Incidence –– Worldwide, 2 million new cases annuallyWorldwide, 2 million new cases annually11

–– United States, 400,000 to 700,000 new cases annuallyUnited States, 400,000 to 700,000 new cases annually22

•• HF afflicts 1000 out of every 100,000 over HF afflicts 1000 out of every 100,000 over age 65 in the U.S.age 65 in the U.S.22

1 1 World Health Statistics, World Health Organization, 1995.World Health Statistics, World Health Organization, 1995.2 American Heart Association, 2001 Heart and Stroke Statistical2 American Heart Association, 2001 Heart and Stroke Statistical Update.Update.

Heart Failure StatisticsHeart Failure Statistics

•• 50% 50% of HF patients have 3 or more of HF patients have 3 or more coco--morbiditiesmorbidities11

•• HF patients take an average of six medicationsHF patients take an average of six medications11

•• 78% of HF patients have had at least two hospital 78% of HF patients have had at least two hospital admissions per yearadmissions per year11

•• Cost of HF in the U.S. is estimated to be between Cost of HF in the U.S. is estimated to be between $10 billion and $38 billion annually$10 billion and $38 billion annually22

•• 55--year survival rate for all NYHA classes estimated year survival rate for all NYHA classes estimated at 50%at 50%33

11 English M and English M and MastreamMastream M. M. CritCrit Care NurseCare Nurse 1995;18:11995;18:1--6.6.22 HavranekHavranek EP, Abraham WT, EP, Abraham WT, The Healthcare Economics of Heart FailureThe Healthcare Economics of Heart Failure 1998; 14:101998; 14:10--18.18.33 American Heart Association, 2001 Heart and Stroke Statistical UpAmerican Heart Association, 2001 Heart and Stroke Statistical Update.date.

Ventricular Ventricular DysynchronyDysynchrony

•• Abnormal ventricular conduction resulting Abnormal ventricular conduction resulting in a mechanical delayin a mechanical delay–– Wide QRS (IVCD); typically LBBB morphologyWide QRS (IVCD); typically LBBB morphology–– Poor systolic functionPoor systolic function–– Impaired diastolic functionImpaired diastolic function

ECG depicting ECG depicting interventricularinterventricular conduction delayconduction delay

Wide QRS Wide QRS ––Proportional Mortality IncreaseProportional Mortality Increase

60%

70%

80%

90%

100%

0 60 120 180 240 300 360Days in Trial

Cum

ulat

ive

Surv

ival

QRS Duration (msec)

<90

90-120

120-170

170-220

>220

Adapted from Adapted from GottipatyGottipaty et al. et al.

•• VesnarinoneVesnarinone StudyStudy11

(VEST study analysis)(VEST study analysis)•• NYHA Class IINYHA Class II--IV patientsIV patients•• 3,654 3,654 ECGsECGs digitally digitally

scannedscanned•• Age, Age, creatininecreatinine, LVEF, heart , LVEF, heart

rate, and QRS duration rate, and QRS duration found to be independent found to be independent predictors predictors of mortalityof mortality

•• Relative risk of widest Relative risk of widest QRS group 5x greater QRS group 5x greater than narrowest ( >200ms than narrowest ( >200ms vsvs< 90ms )< 90ms )

11 GottipatyGottipaty V, V, KrelisKrelis S, et al. ACC 1999 [Abstr];847S, et al. ACC 1999 [Abstr];847--4.4.

Animation Animation –– Ventricular Ventricular DysynchronyDysynchrony

Etiology of Ventricular Etiology of Ventricular DysynchronyDysynchrony

•• What Causes Ventricular Dysynchrony?What Causes Ventricular Dysynchrony?11

–– InterInter-- or or intraventricularintraventricular conduction delays usually conduction delays usually manifested as left bundle branch blockmanifested as left bundle branch block

–– Regional wall motion abnormalities with increased Regional wall motion abnormalities with increased workload and stressworkload and stress——compromising ventricular mechanicscompromising ventricular mechanics

–– Disruption of myocardial collagen matrix impairing electrical Disruption of myocardial collagen matrix impairing electrical conduction and mechanical efficiencyconduction and mechanical efficiency

•• Estimated that 15% of all HF patients have Estimated that 15% of all HF patients have ventricular dysynchronyventricular dysynchrony22

11 TavazziTavazzi L. L. EurEur Heart J 2000;21:1211Heart J 2000;21:1211--1214.1214.22 ShenkmanShenkman et al. et al. CirculationCirculation 2000; 102(18):Suppl II, abstract 2293.2000; 102(18):Suppl II, abstract 2293.

Clinical Consequences of Clinical Consequences of Ventricular Ventricular DysynchronyDysynchrony

•• Abnormal Abnormal interventricularinterventricularseptalseptal wall wall motionmotion11

•• Reduced Reduced dP/dtdP/dt33

•• Reduced Reduced diastolic filling diastolic filling timetime1,21,2

•• Prolonged MR Prolonged MR durationduration1,21,2

11 GrinesGrines CL, CL, BashoreBashore TM, TM, BoudoulasBoudoulas H, et al. H, et al. CirculationCirculation 1989;79:8451989;79:845--853.853.2 2 Xiao, HB, Lee CH, Gibson DG. Xiao, HB, Lee CH, Gibson DG. Br Heart J Br Heart J 1991;66:4431991;66:443--447.447.33 Xiao HB, Xiao HB, BreckerBrecker SJD, Gibson DG. SJD, Gibson DG. Br Heart J Br Heart J 1992;68:4031992;68:403--407.407.

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

•• The therapeutic intent of The therapeutic intent of atrialatrial--synchronized, biventricular pacing synchronized, biventricular pacing is to restore ventricular synchronyis to restore ventricular synchrony

•• Complements drug therapyComplements drug therapy

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

GoalsGoals

•• Improve Improve hemodynamicshemodynamics

•• Improve Quality of LifeImprove Quality of Life

•• Reduce death Reduce death

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

•• Cardiac resynchronization, Cardiac resynchronization, in association with an in association with an optimized AV delay, optimized AV delay, improves improves hemodynamichemodynamicperformance by forcing the performance by forcing the left ventricle to complete left ventricle to complete contraction and begin contraction and begin relaxation earlier, allowing relaxation earlier, allowing an increase in ventricular an increase in ventricular filling time.filling time.

•• Coordinate activation of the Coordinate activation of the ventricles and septum.

ECG depicting IVCDECG depicting IVCD

ECG depicting cardiac resynchronizationECG depicting cardiac resynchronization

ventricles and septum.

Achieving Cardiac ResynchronizationAchieving Cardiac ResynchronizationMechanical Goal: Pace Right and Left VentriclesMechanical Goal: Pace Right and Left Ventricles

•• TransvenousTransvenous ApproachApproach–– Standard pacing leads in RA and RVStandard pacing leads in RA and RV–– Specially designed left heart lead placed in a left ventricular Specially designed left heart lead placed in a left ventricular cardiac vein cardiac vein

via the coronary sinusvia the coronary sinus

Cardiac Resynchronization SystemCardiac Resynchronization System

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• Improved Improved Contraction Contraction PatternPattern

•• AV Interval AV Interval OptimizationOptimization

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• Improved Contraction Improved Contraction PatternPattern

–– Improves Improves interventricularinterventricularsynchronysynchrony1,2,31,2,3

–– Reduces paradoxical Reduces paradoxical septalseptal wall motionwall motion

–– Improves LV regional Improves LV regional wall motionwall motion

–– Lowers endLowers end--systolic systolic volumesvolumes

–– Improves LV Improves LV dP/dt

LV WallLV WallEndocardiumEndocardium

RVRVSeptumSeptum

LVLV

dP/dt

ResynchResynch OFF OFF ResynchResynch ONONCourtesy of Ottawa Heart InstituteCourtesy of Ottawa Heart Institute

1 1 KerwinKerwin et al.et al. JACC 2000; 35:1221JACC 2000; 35:1221--1227. 1227. 22 Le Rest et al. J Le Rest et al. J NuclNucl CardiolCardiol. 1999;6:651. 1999;6:651--656.656.33 Saxon et al. J Saxon et al. J CardiovascCardiovasc ElectrophysiolElectrophysiol 1998;9:131998;9:13--21.21.

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• Improved Contraction Improved Contraction PatternPattern–– Improves Improves

interventricularinterventricularsynchronysynchrony1,2,31,2,3

–– Reduces paradoxical Reduces paradoxical septalseptal wall motionwall motion

–– Improves LV regional Improves LV regional wall motionwall motion

–– Lowers Lowers endend--systolic systolic volumesvolumes1,2,31,2,3

–– Improves LV Improves LV dP/dt

Adapted from Adapted from KassKass et al.et al.

0

40

80

120

0 100 200 300

0

40

80

120

0 100 200 3000

40

80

120

0 100 200 300

0

40

80

120

0 100 200 300

LV P

ress

ure

(mm

Hg)

LV P

ress

ure

(mm

Hg)

LV Volume (mL) LV Volume (mL)

RV Apex RV Septum

LV Free Wall Biventricular

----- NSR Control - - - VDD Pacing

dP/dt

11 KassKass et al. Circulation. 1999;99:1567.et al. Circulation. 1999;99:1567.22 Walker et al. Walker et al. EuropaceEuropace 2000;I(suppl D):abstract 212/5.2000;I(suppl D):abstract 212/5.33 PorcianiPorciani et al. et al. EurEur Heart J Heart J SupplSuppl 2000;2:J232000;2:J23--J30.J30.

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• Improved Contraction PatternImproved Contraction Pattern–– Improves Improves interventricularinterventricular

synchronysynchrony–– Reduces paradoxical Reduces paradoxical

septalseptal wall motionwall motion–– Improves LV regional wall Improves LV regional wall

motionmotion–– Lowers endLowers end--systolic systolic

volumesvolumes–– Improves Improves

LV dP/dtLV dP/dt1,21,2

•• AV Interval OptimizationAV Interval Optimization–– Reduces Reduces mitralmitral

regurgitationregurgitation–– Increases diastolic filling Increases diastolic filling

timetime–– Improves Improves

LV dP/dtLV dP/dt1,2

0

6

12

18

24

30

0 0.25 0.5 0.75 1

AV delay / (PR-30 ms)

% C

hang

e LV

+dP

/dt

RVLVBV

Adapted from Adapted from AuricchioAuricchio et alet al1,2

11 KassKass et al. Circulation. 1999;99:1567.et al. Circulation. 1999;99:1567.22 AuricchioAuricchio et al. Circulation. 1999;99:2993.et al. Circulation. 1999;99:2993.

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• AV Interval OptimizationAV Interval Optimization–– Reduces Reduces mitralmitral

regurgitationregurgitation1,2,31,2,3

–– Increases diastolic Increases diastolic filling timefilling time

–– Improves LV Improves LV dP/dtdP/dt

11 Nishimura et al. J Am Nishimura et al. J Am CollColl CardiolCardiol.. 1995; 25:281.1995; 25:281.22 Walker et al. Walker et al. EuropaceEuropace 2000;I(suppl D): abstract 212/5. 2000;I(suppl D): abstract 212/5. 33 BreckerBrecker et al.et al. Lancet. 1992;340:1308.Lancet. 1992;340:1308.

Proposed Mechanisms of Proposed Mechanisms of Cardiac ResynchronizationCardiac Resynchronization

•• AV Interval OptimizationAV Interval Optimization–– Reduces Reduces mitralmitral

regurgitationregurgitation–– Increases diastolic Increases diastolic

filling timefilling time1,2,31,2,3

–– Improves LV Improves LV dP/dtdP/dt

11 PorcianiPorciani et al. et al. EurEur Heart J Heart J SupplSuppl 2000; 2: J232000; 2: J23--J30.J30.22 Duncan et al. J Am Duncan et al. J Am CollColl CardiolCardiol.. 2001; ACC abstract.2001; ACC abstract.33 Walker et al. Walker et al. EuropaceEuropace 2000;I(suppl D): abstract 212/5.2000;I(suppl D): abstract 212/5.

CRT Improves Cardiac Function at CRT Improves Cardiac Function at Diminished Energy CostDiminished Energy Cost

0.14

0.16

0.18

0.20

0.22

0.24

500 600 700 800 900 1000

dP/dtmax (mmHg/s)

MVO

2/H

R (R

elat

ive

Uni

ts)

LV Pacing

Dobutamine

p< 0.05

Nelson et al. Nelson et al. CirculationCirculation 2000;102:30532000;102:3053--3059.3059.

Is Cardiac Resynchronization Is Cardiac Resynchronization ProPro--arrhythmic?arrhythmic?

0.010.0187 87 ±± 14214217 17 ±± 2020Ventricular Arrhythmia Ventricular Arrhythmia Duration (min)Duration (min)

0.020.0276 76 ±± 1471471 1 ±± 33PVC RunsPVC Runs

NSNS3,394 3,394 ±± 2,9702,9701,255 1,255 ±± 1,5351,535PVC CountPVC Count

PPWithout CRWithout CRWith CRWith CRSinus Rhythm Group; N=12Sinus Rhythm Group; N=12

Walker, et al. Walker, et al. Am J Am J CardiolCardiol 2000;86:2312000;86:231--3.3.

Randomized Clinical TrialsRandomized Clinical Trials

•• MIRACLEMIRACLE–– MulticenterMulticenter InSyncInSync Randomized Clinical EvaluationRandomized Clinical Evaluation

•• MUSTICMUSTIC–– MultisiteMultisite Stimulation in Stimulation in CardiomyopathyCardiomyopathy

Data from these trials document symptomatic improvement and Data from these trials document symptomatic improvement and increased exercise capacity in patients who have moderate to increased exercise capacity in patients who have moderate to severe heart failure and ventricular severe heart failure and ventricular dysynchronydysynchrony when treated with when treated with cardiac resynchronization therapy.cardiac resynchronization therapy.

Measurable OutcomesMeasurable Outcomes

•• NYHA functional classification NYHA functional classification •• Quality of LifeQuality of Life•• 66--Minute Hall Walk DistanceMinute Hall Walk Distance•• Peak VOPeak VO22

MIRACLEMIRACLEMulticenterMulticenter InSyncInSync Randomized Clinical EvaluationRandomized Clinical Evaluation

Abraham WT, Fisher WG, Smith AL. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346:1845-1853

IntroductionIntroduction

•• Early studies of CRT have demonstrated Early studies of CRT have demonstrated improvement in patient symptoms and improvement in patient symptoms and exercise capacity, but exercise capacity, but have been limited byhave been limited by–– Small numbers of enrolled patientsSmall numbers of enrolled patients–– Uncontrolled or poorly controlled study designsUncontrolled or poorly controlled study designs–– UnblindedUnblinded or singleor single--blinded nature of followblinded nature of follow--upup

MIRACLE Study PurposeMIRACLE Study Purpose

•• To compare the effect of CRT versus To compare the effect of CRT versus no CRT on Quality of Life and functional no CRT on Quality of Life and functional capacity in patients with chronic heart capacity in patients with chronic heart failure and ventricular failure and ventricular dysynchronydysynchrony

•• To assess the safety of CRT using the To assess the safety of CRT using the Medtronic Medtronic InSyncInSync®® System in patients System in patients with moderate to severe heart failure with moderate to severe heart failure (NYHA functional Class III/IV)(NYHA functional Class III/IV)

MIRACLE Study MethodologyMIRACLE Study Methodology

CRT CRT

BaselineBaseline ImplantImplantAttemptAttempt

SuccessfulSuccessfulImplantImplant

PrePre--dischargedischargeRandomizationRandomization

≤≤ 11week

StableStableMedicalMedicalTherapyTherapy

weekControlControl DoubleDouble

BlindedCRT CRT

Blinded

1, 3, 61, 3, 6Month Month

FollowupFollowup

•• Control: VDI mode, 30 Control: VDI mode, 30 bpmbpm

•• Treatment (CRT): VDD mode, 30 Treatment (CRT): VDD mode, 30 bpmbpm

•• Intent to treat analysesIntent to treat analyses

•• Heart Failure staff and patients blindedHeart Failure staff and patients blinded

•• EP staff EP staff unblindedunblinded

•• Early crossover prohibited, except for Early crossover prohibited, except for development of development of bradycardiabradycardia pacing pacing indicationindication

1, 3, 61, 3, 6Month Month

FollowupFollowup

CRT CRT

LongLong--term Followterm Follow--up up every 6 Months every 6 Months

..

MIRACLE Study PopulationMIRACLE Study Population

•• Symptomatic patients with heart failureSymptomatic patients with heart failure•• ≥≥ 18 years of age18 years of age•• NYHA Functional Class III or IVNYHA Functional Class III or IV•• QRS duration QRS duration ≥≥ 130 130 msecmsec•• LVEF LVEF ≤≤ 35% by echocardiography35% by echocardiography•• LVEDD LVEDD ≥≥ 55 mms (echo measure)55 mms (echo measure)•• Stable HF medical regimen for Stable HF medical regimen for ≥≥ 11--monthmonth

–– ACEACE--I or substitute, if toleratedI or substitute, if tolerated–– ββ--blocker blocker -- stable regimen for stable regimen for ≥≥ 33--monthsmonths

MIRACLE Pivotal Phase MIRACLE Pivotal Phase Primary Safety and Implant Success ResultsPrimary Safety and Implant Success Results

•• Implant success rate Implant success rate -- 93%93%(536/579 patients)(536/579 patients)

•• Exceeded all device, leads, and system Exceeded all device, leads, and system safety performance criteriasafety performance criteria

..

MIRACLE Pivotal Phase MIRACLE Pivotal Phase CRT Improves 6CRT Improves 6--Minute Hall Walk DistanceMinute Hall Walk Distance

250

300

350

Met

ers

Base-line

1 Month

3Months

6Months

P=0.033P=0.004P=0.032

CRTN=121

ControlN=116

MIRACLE Pivotal Phase MIRACLE Pivotal Phase CRT Improves Quality of LifeCRT Improves Quality of Life

30

40

50

60

70Baseline 1 Month 3 Months 6 Months

Control N=114 CRT N=121

P=0.013P=0.051P=0.020

Total Score

Impr

ovem

ent

MIRACLE Pivotal Phase MIRACLE Pivotal Phase CRT Improves NYHA ClassCRT Improves NYHA Class

93%

64%

90%

32%

27%

52%

13%

0%

20%

40%

60%

80%

100%

Baseline 6-Months Baseline 6-Months

IIIIIIIV

P < 0.001

Control (N = 117) CRT(N = 124) Chi-square test

Class

MIRACLE Pivotal Phase MIRACLE Pivotal Phase Effects of CRT on Metabolic Exercise TestingEffects of CRT on Metabolic Exercise Testing

Peak VO2

1213

1415

1617

ControlN=80

CRTN=87

ml/k

g/m

in

Baseline 6-Months

P=0.056

Total Exercise Time

360420

480540

600660

ControlN=80

CRTN=88

Seco

nds

Baseline 6-Months

P<0.001

MIRACLE Pivotal Phase MIRACLE Pivotal Phase Effects of CRT on Effects of CRT on EchocardiographicEchocardiographic ParametersParameters

LVEDD

6.50

6.75

7.00

7.25

7.50

ControlN=63

CRTN=61

Cen

timet

ers

Baseline 6-Months

P<0.001

LVEF

1015

2025

3035

ControlN=81

CRTN=63

Perc

enta

ge

Baseline 6-Months

P<0.001

MIRACLE Pivotal PhaseMIRACLE Pivotal PhaseEffect of CRT on Composite ResponseEffect of CRT on Composite Response

38%

63%

0%

10%

20%

30%

40%

50%

60%

70%

Improved No Change Worsened

Prop

ortio

n

Control N=132 CRT N=134Chi-square test

P < 0.001

33%

15%

29%22%

MIRACLE Pivotal Phase MIRACLE Pivotal Phase ConclusionsConclusions

•• In NYHA Class III and IV heart failure In NYHA Class III and IV heart failure patients with patients with intraventricularintraventricular conduction conduction delays who are on stable, optimal medical delays who are on stable, optimal medical therapy, cardiac resynchronization therapytherapy, cardiac resynchronization therapy–– is safe and well toleratedis safe and well tolerated–– improves quality of life, functional class, and exercise capacitimproves quality of life, functional class, and exercise capacityy–– improves cardiac structure and functionimproves cardiac structure and function–– improves heart failure composite responseimproves heart failure composite response

Kaplan-Meier Estimates of the Time to Death or Hospitalization for Worsening Heart Failure in the Control and Resynchronization Groups

Abraham, W. T. et. al. N Engl J Med 2002;346:1845-1853

MUSTIC Trial

Change in outcome measures with active pacing in MUSTIC Change in outcome measures with active pacing in MUSTIC

Outcome Outcome measure

p valuep value

HospitalizationsHospitalizations <0.05<0.05

measure% change

Cazeau et al. N Engl J Med 2001; 344: 873-80.

<0.001<0.001

Quality of life Quality of life score

Mean (Mean (++SD) SD) distance distance walked

+23%walked

+32%+32% <0.001score

+8% <0.03Peak oxygen uptake

-66%

COMPANION Trial COMPANION Trial

•• Comparison of Medical Therapy, Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trialHeart Failure (COMPANION) trial

•• a parallel, randomized clinical trial in a parallel, randomized clinical trial in 1600 patients with moderate or 1600 patients with moderate or severe heart failure with QRS >120 severe heart failure with QRS >120 ms and Pms and P--R interval >150 msR interval >150 ms

COMPANION TrialCOMPANION Trial

•• allall--cause death and allcause death and all--cause cause hospitalizations (> 12 months ) hospitalizations (> 12 months ) reduced by 19 % for both the CRT reduced by 19 % for both the CRT and CRTand CRT--D arms . D arms .

•• AllAll--cause mortality reduction to cause mortality reduction to 43.4%43.4%----CRTCRT--D armsD arms

•• allall--cause, cardiovascular, or heart cause, cardiovascular, or heart failure hospitalizations was likely due failure hospitalizations was likely due to CRTto CRT

CRT on death and hospitalization

•• A metaA meta--analysis of 4 randomized analysis of 4 randomized controlled clinical trials controlled clinical trials

•• CONTAK CD, CONTAK CD, InSyncInSync ICD, MIRACLE, and ICD, MIRACLE, and MUSTIC trialsMUSTIC trials

•• reduces mortality from progressive heart reduces mortality from progressive heart failure by 51%failure by 51%

cardiac resynchronization on death and hospitalization

0.71 0.71 (0.53(0.53--0.96)0.96)

17.417.413.013.0HF hospitalizationHF hospitalization

0.77 0.77 (0.51(0.51--1.18)1.18)

6.36.34.94.9AllAll--cause mortalitycause mortality

1.15 1.15 (0.65(0.65--2.02)2.02)

2.82.83.23.2NonNon--HF mortalityHF mortality

0.49 0.49 (0.25(0.25--0.93)0.93)

3.53.51.71.7ProgressiveProgressiveHF mortalityHF mortality

OR OR (95% CI)(95% CI)

No CR No CR (%)(%)

CR (%)CR (%)EventEvent

CR=cardiac resynchronizationOR=odds ratio

Bradley DJ et al. JAMA 2003; 289:730-740.

CRT Also effective in narrow QRSCRT Also effective in narrow QRS

•• asynchrony can also occur in heartasynchrony can also occur in heart--failure failure patients with an incomplete left bundle patients with an incomplete left bundle branch block (or "narrow QRS").branch block (or "narrow QRS").

•• improvements in NYHA functional class, improvements in NYHA functional class, left ventricular ejection fraction, left left ventricular ejection fraction, left ventricular endventricular end--diastolic and enddiastolic and end--systolic systolic diameter, and diameter, and mitralmitral regurgitation arearegurgitation area

•• Better tools needed to measure Better tools needed to measure synchrony !synchrony !

J Am Coll Cardiol 2003 Dec 17; 42(12):2117-24.

Is left ventricular pacing just as Is left ventricular pacing just as good? good?

•• compared during a threecompared during a three--month month period of active (period of active (univentricularuniventricular) ) pacing and a threepacing and a three--month period of month period of inactive pacing.inactive pacing.

•• exercise tolerance, heartexercise tolerance, heart--failure failure severity, and quality of life all severity, and quality of life all significantly improvedsignificantly improved

J Am Coll Cardiol 2003 Dec 17; 42(12):2109-16.

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

Patient Selection,Patient Selection, Implant Implant and Followand Follow--up Careup Care

Indications for the Cardiac Indications for the Cardiac Resynchronization SystemResynchronization System

•• indicated for the reduction indicated for the reduction of symptoms in patients that of symptoms in patients that meet the following criteria:meet the following criteria:–– Symptomatic despite stable, optimal Symptomatic despite stable, optimal

medical therapymedical therapy–– Moderate to severe heart failure Moderate to severe heart failure

(NYHA Class III/IV)(NYHA Class III/IV)–– QRS QRS ≥≥ 130 ms130 ms–– LV ejection fraction LV ejection fraction ≤≤ 35%35%

Implant Process OverviewImplant Process Overview

Implant success rates from the MUSTICImplant success rates from the MUSTIC11and and MIRACLEMIRACLE22 Trials were 92% and 93% respectivelyTrials were 92% and 93% respectively

•• Insertion of three leads (RV, LV, RA) Insertion of three leads (RV, LV, RA) –– Left heart lead placement in a left ventricular cardiac vein viaLeft heart lead placement in a left ventricular cardiac vein via the the

coronary sinuscoronary sinus

•• Implantation of cardiac resynchronization Implantation of cardiac resynchronization devicedevice–– Similar to standard pacemaker implant procedureSimilar to standard pacemaker implant procedure

•• Measurement of final thresholds and Measurement of final thresholds and programming of deviceprogramming of device

11 CazeauCazeau S, S, LeclercqLeclercq C, et al. C, et al. N N EnglEngl J MedJ Med 2001; 344:8732001; 344:873--880.880.22 Abraham WT, et al. ACC 2001 Scientific Sessions.Abraham WT, et al. ACC 2001 Scientific Sessions.

Animation Animation –– LV Lead PlacementLV Lead Placement

Implant Dissection/Perforation EventsImplant Dissection/Perforation Events579 Implant Procedures579 Implant Procedures**

6 (1.0)6 (1.0)

2 (0.3)2 (0.3)

4 (0.7)4 (0.7)

ComplicationComplicationN ( %)N ( %)

35352929TotalTotal

12121010Cardiac Cardiac vein/CS vein/CS PerforationPerforation

23231919CS CS DissectionDissection

TotalTotalNN

ObservationObservationN

EventEventN

All events were resolved without further All events were resolved without further sequelaesequelae. . **Includes patient attempts from all study phases.Includes patient attempts from all study phases.

FollowFollow--up Careup Care

•• Standard medical management of HF as Standard medical management of HF as defined by practice guidelinesdefined by practice guidelines

•• Standard device followStandard device follow--up as defined by up as defined by practice guidelinespractice guidelines–– Goal is to achieve 100% biventricular pacing to deliver therapyGoal is to achieve 100% biventricular pacing to deliver therapy–– AV interval optimization is recommended to achieve maximum AV interval optimization is recommended to achieve maximum

diastolic filling timediastolic filling time

In SummaryIn Summary

Cardiac Resynchronization therapy offers an Cardiac Resynchronization therapy offers an adjunctive approach for treating patients with adjunctive approach for treating patients with ventricular ventricular dysynchronydysynchrony in the setting of in the setting of moderate to severe heart failure who are on moderate to severe heart failure who are on optimal, stable medical therapy.optimal, stable medical therapy.

Thank youThank you