device therapy in heart failure teresa m. menendez hood, m.d., f.a.c.c

Device Therapy in Device Therapy in Heart FailureHeart Failure

Teresa M. Menendez Hood, M.D., F.A.C.C.

Heart FailureHeart Failure

400,000 5.0 million 250,000

Annual Incidence

Heart Failure Prevalence

Annual Mortality

U.S.

Up to 30 % of HF patients have an IVCD (80% with a Up to 30 % of HF patients have an IVCD (80% with a LBBB) which has been linked to increases in mortality LBBB) which has been linked to increases in mortality and morbidity.and morbidity.

HF is the HF is the leading cause of hospitalizationsleading cause of hospitalizations in the US in the US and uses up 5% of the health care costs and uses up 5% of the health care costs

2% of the population and 6% of the population >65 2% of the population and 6% of the population >65 Prevalence is on the rise.Prevalence is on the rise.

Heart Failure BackgroundHeart Failure BackgroundAt Risk for Heart At Risk for Heart

FailureFailureHeart FailureHeart Failure

Stage A Stage A

At high risk of HF but At high risk of HF but without structural heart without structural heart disease or HF symptomsdisease or HF symptoms

Stage CStage C

Structural heart Structural heart disease with prior or disease with prior or current HF symptomscurrent HF symptoms

Stage BStage B

Structural heart disease Structural heart disease but without signs or but without signs or symptoms of HFsymptoms of HF

Stage DStage D

Refractory HF Refractory HF requiring specialized requiring specialized interventionsinterventions

Class I

Asymptomatic heart failure

ejection fraction (EF) <40%

Class II

Mild symptomatic heart failurewith ordinary

exertion

Class IV

Symptomatic heart failure

at rest

Class III

Moderatesymptomatic heart failure

with less thanordinary exertion

NYHA Class-evaluates the disability NYHA Class-evaluates the disability imposed on the patient who already has imposed on the patient who already has

structural heart diseasestructural heart disease

Stages of Heart FailureStages of Heart Failure

Leading Causes of Death in the Leading Causes of Death in the U.S.U.S.

National Vital Statistics Report. Oct. 12, 2001;49(11).MMWR. State-specific mortality from sudden cardiac death – US 1999. Feb 15, 2002;51:123-126.

0% 5% 10% 15% 20% 25%

Septicemia

Nephritis

Alzheimer’s Disease

Influenza/pneumonia

Diabetes

Accidents/injuries

Chronic lower respiratory diseases

Cerebrovascular disease

Other cardiac causes

All cancers

You must combine deaths from all cancers to outnumber the deaths from SCA each year.

All other causes

Sudden cardiac arrest (SCA)

17

8

20

15

9

19

76

4

11

0

10

20

30

CHF-STAT GESICA SOLVD V-HeFT I MERIT-HF CIBIS-II CARVEDILOL-US

Con

trol

Gro

up M

orta

lity

Total Mortality

Sudden Death

SCD accounts for ~50% of the total deaths.

12 months 16 months41.4 months 27 months 13 months45 months 6 months

SCD Rates in CHF Patients with LV SCD Rates in CHF Patients with LV DysfunctionDysfunction

60%

70%

80%

90%

100%

0 60 120 180 240 300 360

Days

Cu

mu

lati

ve S

urv

ival

Duration (msec)

<90

90 120

120 170

170 220

• QRS duration is an independent predictor of mortality (>140 ms)

• Other factors are: age, creatinine, EF, and HR

.

-

-

-

QRS

-

-

-

>220

SCD in Heart FailureSCD in Heart Failure

Degree of SCD risk by classDegree of SCD risk by classMortality in NYHA class II is 5 to 15% Mortality in NYHA class II is 5 to 15%

50 to 80%50 to 80% of the deaths are of the deaths are SuddenSudden

Mortality in NYHA class III is 20 to 50% Mortality in NYHA class III is 20 to 50% Up to Up to 50%50% of the deaths are of the deaths are SuddenSudden

Mortality in NYHA class IV is 30 to 70%Mortality in NYHA class IV is 30 to 70%5 to 30%5 to 30% of deaths are of deaths are SuddenSudden (more deaths from (more deaths from

pump failure)pump failure)

SCD in Heart FailureSCD in Heart Failure

Right Ventricular PacingRight Ventricular Pacing

RV apex pacing is harmful RV apex pacing is harmful in patients in patients with LV dysfunctionwith LV dysfunction. Became evident . Became evident in multiple pacer and ICD trials that it in multiple pacer and ICD trials that it increases HF by producing a “paced” increases HF by producing a “paced” LBBB.LBBB.

Abnormal LV activationAbnormal LV activationReduced stroke volume Reduced stroke volume

Detrimental RV pacingDetrimental RV pacing

MADIT II (2002) had a survival benefit MADIT II (2002) had a survival benefit with the ICD but in a subgroup analysis, with the ICD but in a subgroup analysis, there was an increase in heart failure there was an increase in heart failure morbidity (more hospitalizations) felt morbidity (more hospitalizations) felt due to forced RV pacing compared to due to forced RV pacing compared to controls in which no pacing was controls in which no pacing was present.present.

MADIT II: ComplicationsMADIT II: Complications

New or Worsening HFNew or Worsening HF

14.9%

19.9%

0.00%

10.00%

20.00%

Conventional Therapy ICD Therapy

(p= 0.09)

N= 490 N= 742

•RV pacing causes ventricular RV pacing causes ventricular dysynchrony and may lead to dysynchrony and may lead to worsening HF.worsening HF.

• Intrinsic ventricular activation Intrinsic ventricular activation is better for ICD patients with is better for ICD patients with left ventricular dysfunction left ventricular dysfunction who do not “need” pacing.who do not “need” pacing.

•<<10% of ICD patients have a 10% of ICD patients have a Class I pacing indication at the Class I pacing indication at the time of implant…they do not time of implant…they do not NEED pacing.NEED pacing.

•Physicians, when appropriate, Physicians, when appropriate, should consider programming should consider programming of ICDs to avoid frequent RV of ICDs to avoid frequent RV pacing.pacing.

ICD indication but ICD indication but nono indication for a indication for a pacemakerpacemaker

EF < 40%EF < 40% DDDR @ 70BPM DDDR @ 70BPM

versus VVI 40 BPMversus VVI 40 BPM

DAVID — Dual Chamber and VVI DAVID — Dual Chamber and VVI Implantable Defibrillator Trial : 2002Implantable Defibrillator Trial : 2002

Search AV Extension and Managed Search AV Extension and Managed Ventricular Pacing for Promoting Ventricular Pacing for Promoting

Atrioventricular Conduction (SAVE PACe) Atrioventricular Conduction (SAVE PACe) Trial : 2007Trial : 2007

1065 patients with sinus-node disease, intact AV 1065 patients with sinus-node disease, intact AV conduction and normal QRS intervalconduction and normal QRS interval

Randomized to conventional dual-chamber pacing Randomized to conventional dual-chamber pacing (n=535) or dual-chamber minimal ventricular pacing (n=535) or dual-chamber minimal ventricular pacing (n=530)(n=530)

―― study tests new pacing algorithm that avoids study tests new pacing algorithm that avoids ventricular pacing except during periods of high-grade ventricular pacing except during periods of high-grade AV blockAV block

With dual-chamber pacing, ↓ frequency RV pacing (9.1% With dual-chamber pacing, ↓ frequency RV pacing (9.1% vs. 99%; p<0.001) and 40% relative risk ↓ in incidence of vs. 99%; p<0.001) and 40% relative risk ↓ in incidence of persistent AFpersistent AF

TheThe ConceptConcept

In In mostmost patients with an IVCD (QRS > 130 ms) , patients with an IVCD (QRS > 130 ms) , the presence of atrial-biventricular (RV + LV) the presence of atrial-biventricular (RV + LV) pacing will provide early stimulation to an pacing will provide early stimulation to an otherwise late segment of electrical activation in otherwise late segment of electrical activation in the LV.the LV.

This This shouldshould translate into an increase in the EF, translate into an increase in the EF, decrease of the LV dimension, improvement in decrease of the LV dimension, improvement in the QOL and NYHA class. the QOL and NYHA class.

This This maymay translate into an decrease in CHF translate into an decrease in CHF exacerbations , hospitalizations and a decrease exacerbations , hospitalizations and a decrease in mortality.in mortality.

The ProofThe Proof

1994 –19971994 –1997: Mechanistic and both short and : Mechanistic and both short and longer term longer term observationalobservational studies. Studies studies. Studies initially used epicardial leads placed by initially used epicardial leads placed by thoracotomy or thorascope. thoracotomy or thorascope. The first BiV pacer was implanted in The first BiV pacer was implanted in 19941994

1998 –19991998 –1999: : Randomized, controlled studiesRandomized, controlled studies to assess exercise capacity, functional status, to assess exercise capacity, functional status, and quality of life.and quality of life. There was development of There was development of transvenoustransvenous leads via leads via

the coronary sinus in to get to the LV.the coronary sinus in to get to the LV.

Cohen TJ, Klein J. J Inva2002;14:48-53.

The ProofThe Proof

2000 – 20062000 – 2006: Randomized, controlled trials to assess : Randomized, controlled trials to assess combined combined mortality and CHF hospitalizationmortality and CHF hospitalization. Also . Also evaluated the evaluated the combined combined benefit of ICD’s with CRT.benefit of ICD’s with CRT.

2006-20082006-2008: Trials to identify patients who will benefit : Trials to identify patients who will benefit from CRT. This uses echocardiographic markers of from CRT. This uses echocardiographic markers of dyssynchrony and the QRS measurement.dyssynchrony and the QRS measurement. 20% of patients do 20% of patients do notnot respond to therapy in clinical trials with a respond to therapy in clinical trials with a

wide QRS and 50% patients with a narrow QRS/CHF have wide QRS and 50% patients with a narrow QRS/CHF have dyssynchrony on echo and may benefit from this therapy.dyssynchrony on echo and may benefit from this therapy.

If the QRS is < 150 ms, then the chance of responding to BiVP If the QRS is < 150 ms, then the chance of responding to BiVP is ~5%. It will be in this patient group of QRS of 120-150 ms is ~5%. It will be in this patient group of QRS of 120-150 ms where preselection of responders would be where preselection of responders would be mostmost valuable. valuable.

The Cardiac The Cardiac Resynchronization Clinical Resynchronization Clinical

TrialsTrials

PATH-CHF, MUSTIC, MIRACLE, PATH-CHF, MUSTIC, MIRACLE, COMPANION, and CARE-HF*COMPANION, and CARE-HF*

*This is not a complete list of all the CRT trials and the dates given *This is not a complete list of all the CRT trials and the dates given are when the trial results were published.are when the trial results were published.

Cumulative Enrollment in Cardiac Cumulative Enrollment in Cardiac Resynchronization Randomized Resynchronization Randomized

TrialsTrials

0

1000

2000

3000

4000

1999 2000 2001 2002 2003 2004 2005

Results Presented

Cum

ulat

ive

Pati

ents

PATH CHF

MUSTIC SR

MUSTIC AF

MIRACLE

CONTAK CD

MIRACLE ICD

PATH CHF II

COMPANION

MIRACLE ICD II

CARE HF

This was the This was the first multicenter trialfirst multicenter trial and used the standard endocardial and used the standard endocardial RV lead and an RV lead and an epicardialepicardial LV lead via thoracotomy or thorascope LV lead via thoracotomy or thorascope

Single blinded RCTSingle blinded RCT 53 centers in 53 centers in EuropeEurope 41 41 patientspatients

PATH-CHF: 1999PATH-CHF: 1999Pacing Therapy for Congestive Heart Failure

PATH-CHFPATH-CHF

Primary endpointsPrimary endpoints Peak VO2Peak VO2 Six-minute walk distanceSix-minute walk distance

Secondary endpointsSecondary endpoints Minnesota Living with Heart Failure score (QOL)Minnesota Living with Heart Failure score (QOL) NYHA classNYHA class EFEF Trend towards decrease in HospitalizationsTrend towards decrease in Hospitalizations

Acute hemodynamic testing revealed that the lateral and Acute hemodynamic testing revealed that the lateral and posterolateral walls were the best target sites.posterolateral walls were the best target sites. The best responders were those with QRS>150 , long PR and dP/dt < 700 The best responders were those with QRS>150 , long PR and dP/dt < 700

mm Hg/smm Hg/s

MUSTIC: 2001MUSTIC: 2001Multicenter Stimulation in CMMulticenter Stimulation in CM

European study with 67 patientsEuropean study with 67 patients QRS>150, CHF, EF <35%QRS>150, CHF, EF <35% BiVP versus backup VVI pacing at 40 BPMBiVP versus backup VVI pacing at 40 BPM Increase in 6 minute walk time , QOL and Peak Increase in 6 minute walk time , QOL and Peak

VO2 with BiVP and persisted for up to 12 monthsVO2 with BiVP and persisted for up to 12 months 60% decrease in CHF hospitalizations 60% decrease in CHF hospitalizations First to use endocardial LV leadsFirst to use endocardial LV leads via the CS via the CS No significant change in mortality, but a trend No significant change in mortality, but a trend

towards an improvement.towards an improvement. Acute hemodynamic studies showed the Acute hemodynamic studies showed the mid mid

lateral walllateral wall to be the best site to be the best site

MIRACLE:2002MIRACLE:2002Multi-center In Sync Randomized Clinical Multi-center In Sync Randomized Clinical

Evaluation TrialEvaluation Trial

Double blinded RCTDouble blinded RCT FirstFirst US trialUS trial Class 3 or 4, on OPT, QRS >130 ms, EF<35%Class 3 or 4, on OPT, QRS >130 ms, EF<35%Enrollment of 453 patientsEnrollment of 453 patients

MIRACLEMIRACLENYHA class III-IVLVEDD > 60 mmQRS > 130 ms

Stable 3 month regimen of beta-blocker/ACE inhibitorEF < 35%

Randomization

CRT on

CRT on

1- and 3-month follow-up

6-month follow-up

CRT off

1- and 3-month follow-up

6-month follow-up

Long-term follow-up

Nonresponders:Nonresponders: older, ischemic CM, no MR, QRS<150 older, ischemic CM, no MR, QRS<150Responders: Responders: had shorter duration on CHF and longer had shorter duration on CHF and longer QRS>155QRS>155

MIRACLEMIRACLE

39%39%34%34%

27%27%

67%67%

17%17% 16%16%

0%0%

20%20%

40%40%

60%60%

ImprovedImproved No ChangeNo Change WorsenedWorsened

Pro

port

ion

Pro

port

ion

Control N=225Control N=225 CRT N=228CRT N=228

P < 0.001P < 0.001

MIRACLEMIRACLE

There was a decrease in hospitalizations of 50% at 6 There was a decrease in hospitalizations of 50% at 6 months and a months and a trend towardstrend towards a decrease in mortality. a decrease in mortality.

All other primary and secondary endpoints were met: 6 All other primary and secondary endpoints were met: 6 minute walk time, peak Vo2, QOL, EF , NYHA class, minute walk time, peak Vo2, QOL, EF , NYHA class, LVEDDLVEDD

Magnitude of improvement Magnitude of improvement notnot influenced by degree of QRS influenced by degree of QRS shortening with BiVP (average in all was –20msec)shortening with BiVP (average in all was –20msec)

FDA ApprovalFDA Approval

The The first CRT devicefirst CRT device was was approved by the FDA in approved by the FDA in

September 2001September 2001 . .

The The first CRT with an ICDfirst CRT with an ICD was was approved by the FDA in approved by the FDA in

May 2002May 2002 . .

MADIT 1MADIT 1 1996 required a positive EP 1996 required a positive EP study;ischemicsstudy;ischemics

MUSTTMUSTT 1999 required a positive EP study; 1999 required a positive EP study; ischemics; EF<40%ischemics; EF<40%

MADIT 2MADIT 2 2002 prior MI (ischemic cardiomyopathy) 2002 prior MI (ischemic cardiomyopathy) and EF<30% (no EP study required) ;60% had CHF and EF<30% (no EP study required) ;60% had CHF and 50% had QRS > 120 ms; resulted in a 31% and 50% had QRS > 120 ms; resulted in a 31% decrease risk of death and halted prematurely due to decrease risk of death and halted prematurely due to the positive effect of the ICD: resulted in the FDA the positive effect of the ICD: resulted in the FDA approving the ICD for primary prevention this patient approving the ICD for primary prevention this patient population, but only those with a QRS > 120 ms.population, but only those with a QRS > 120 ms.

The Primary ICD Prevention TrialsThe Primary ICD Prevention Trials

The Primary ICD Prevention TrialsThe Primary ICD Prevention Trials

SCD-HeftSCD-Heft - - 2005 2005 The SCD-Heft trial The SCD-Heft trial resulted in resulted in FDA approval of the ICD FDA approval of the ICD January 2005January 2005 in patients with CHF and in patients with CHF and EF<35 % that included EF<35 % that included bothboth ischemic ischemic and nonischemic cardiomyopathy for and nonischemic cardiomyopathy for primary prevention primary prevention withoutwithout a positive a positive EP study EP study oror ventricular ectopy . ventricular ectopy . NoNo QRS cutoff was required.QRS cutoff was required.

COMPANION:2004COMPANION:2004

• OPT1

• OPT

• CRT+

2

• OPT

• CRT-D+

2

Randomization

Comparison of Medical Therapy, Pacing and

Defibrillation in Heart Failure

COMPANIONCOMPANION Enrolled 1520 patients class 3 and 4, QRS >120msEnrolled 1520 patients class 3 and 4, QRS >120ms Primary endpointPrimary endpoint: death or hospitalization for any : death or hospitalization for any

causecause CRT CRT metmet the primary endpoints and the CRT +/- ICD the primary endpoints and the CRT +/- ICD

significantly reduces mortalitysignificantly reduces mortality This was the This was the first to show mortality benefitfirst to show mortality benefit from CRT from CRT

alonealone Showed that patients with CRT also benefit from ICD Showed that patients with CRT also benefit from ICD

therapytherapy OPT had SCD in OPT had SCD in 36%,36%, 23%23% in CRT and in CRT and 3%3% in CRT+ICD in CRT+ICD

• CRT arm had 20% reduction in mortality and CRT arm had 20% reduction in mortality and hospitalization over OPT arm but it was not hospitalization over OPT arm but it was not statistically significantstatistically significant

• Significant reduction in CRT-ICD arm of 40% for Significant reduction in CRT-ICD arm of 40% for mortality over OPT arm (19% in OPT and 11% in mortality over OPT arm (19% in OPT and 11% in CRT-ICD group)CRT-ICD group)

• Study was halted prematurely due to its positive Study was halted prematurely due to its positive benefit.benefit.

• Mean follow up was 16 monthsMean follow up was 16 months

COMPANIONCOMPANION

CARE-HFCARE-HFCACArdiac rdiac REREsynchronization synchronization

in in HHeart eart FFailureailure 2005 2005

The effect of cardiac resynchronization on morbidity The effect of cardiac resynchronization on morbidity and mortality in heart failure in 813 patients in and mortality in heart failure in 813 patients in EuropeEurope ( prospective multicenter RCT) with ( prospective multicenter RCT) with completed enrollment by 2002completed enrollment by 2002

Large patient size and length of trial (average follow Large patient size and length of trial (average follow up of up of 29 months29 months) allowed ability to asses effects of ) allowed ability to asses effects of CRTCRT

Looked at CRT alone (Looked at CRT alone (no ICDno ICD)) Patients with class 3 or 4, EF < 35%, QRS >120 msPatients with class 3 or 4, EF < 35%, QRS >120 ms There was a There was a 37%37% reduced mortality reduced mortality oror first first

hospitalization for a cardiac cause compared to OPT hospitalization for a cardiac cause compared to OPT

CARE-HFCARE-HF All endpoints were met : EF, NYHA, QOL, BNP, Echo All endpoints were met : EF, NYHA, QOL, BNP, Echo

and hemodynamic parametersand hemodynamic parameters 33%33% of the deaths in the CRT group were due to SCD of the deaths in the CRT group were due to SCD For every 9 devices, one death and 3 hospitalizations For every 9 devices, one death and 3 hospitalizations

were preventedwere prevented Echo criteria in patients with QRS Echo criteria in patients with QRS 120-149ms120-149ms to look for to look for

dyssynchrony (had to have 2 of 3)…the “gray area dyssynchrony (had to have 2 of 3)…the “gray area group”group” Aortic pre-ejection delay of > 140 ms ( onset of QRS to Aortic Aortic pre-ejection delay of > 140 ms ( onset of QRS to Aortic

ejection)ejection) Interventricular mechanical delay of >40 ms ( RV-LV)Interventricular mechanical delay of >40 ms ( RV-LV) Delayed activation of the postero-lateral LV wall (>50ms)Delayed activation of the postero-lateral LV wall (>50ms)

Primary EndpointPrimary Endpoint(All-cause Mortality or Unplanned Hosp. (All-cause Mortality or Unplanned Hosp.

for Major CVS Event)for Major CVS Event)

CRT : 159 pts (39%)

334848118118232232292292404404Medical TherapyMedical Therapy

776868166166273273323323409409CRTCRT

Number at riskNumber at risk0 500 1000 1500

0.00

0.25

0.50

0.75

1.00HR 0.63 (95% CI 0.51 to 0.77)

Eve

nt-

free

Su

rviv

al

Days

P < .0001

Medical : 224 ptsTherapy (55 %)

ConclusionsConclusions Conclusive results from CARE-HF demonstrate that CRT Conclusive results from CARE-HF demonstrate that CRT

should be considered as part of should be considered as part of routineroutine therapy for therapy for patients with moderate to severe HF due to LVSD with patients with moderate to severe HF due to LVSD with evidence (ECG supported by Echo) of cardiac evidence (ECG supported by Echo) of cardiac dyssynchrony to*:dyssynchrony to*:

Improve cardiac function and efficiencyImprove cardiac function and efficiency

Improve symptoms and QoLImprove symptoms and QoL

Reduce morbidityReduce morbidity

Prolong survivalProlong survival

These benefits are in addition to those of optimal These benefits are in addition to those of optimal pharmacological therapy (OPT)pharmacological therapy (OPT)

The The ReResynchronization synchronization ThTherapy erapy iin n NNormal ormal

QQRS (RethinQ) StudyRS (RethinQ) Study20072007

BackgroundBackground

Currently, indications for cardiac resynchronization therapy (CRT) Currently, indications for cardiac resynchronization therapy (CRT) include QRS duration include QRS duration >> 120ms, LVEF 120ms, LVEF << 35% and NYHA 35% and NYHA

Class III-IV.Class III-IV. 20-30% of patients do not respond to CRT despite application of 20-30% of patients do not respond to CRT despite application of

established selection criteria. established selection criteria.

Patients with normal conduction or a slightly prolonged QRS Patients with normal conduction or a slightly prolonged QRS duration also exhibit mechanical abnormalities due to duration also exhibit mechanical abnormalities due to intraventricular dyssynchrony.intraventricular dyssynchrony.

Myocardial Tissue Doppler Imaging (TDI) allows both the velocity Myocardial Tissue Doppler Imaging (TDI) allows both the velocity and timing of regional longitudinal motion to be measured.and timing of regional longitudinal motion to be measured.

LV dyssynchrony may also be useful in predicting the benefit of LV dyssynchrony may also be useful in predicting the benefit of

CRT before implantation of the pulse generator. CRT before implantation of the pulse generator.

HypothesisHypothesis

We hypothesized that patients with NYHA We hypothesized that patients with NYHA class III, left ventricular ejection fraction class III, left ventricular ejection fraction less than or equal to 35%, narrow QRS less than or equal to 35%, narrow QRS duration < 130 ms, and evidence of duration < 130 ms, and evidence of mechanical dyssynchrony on mechanical dyssynchrony on echocardiography may benefit from cardiac echocardiography may benefit from cardiac resynchronization therapy.resynchronization therapy.

Mechanical dyssynchrony considered present if either

M-Mode - Septal posterior wall mechanical delay (SPWMD) ≥ 130 ms

OR

Tissue Doppler Imaging (TDI) of the basal ventricular segments in apical 4/2/3 chamber views - Septal to lateral delay ≥ 65ms OR - Antero-septal to posterior delay ≥ 65ms

Echo Criteria for LV DyssynchronyEcho Criteria for LV Dyssynchrony

Summary:RethinQSummary:RethinQThis prospective, multi-center, randomized trial was This prospective, multi-center, randomized trial was

designed to evaluate the effectiveness of CRT therapy designed to evaluate the effectiveness of CRT therapy in a HF population with narrow QRS duration and in a HF population with narrow QRS duration and evidence of mechanical dyssynchrony.evidence of mechanical dyssynchrony.

There was no statistical significant difference in the There was no statistical significant difference in the change in Peak VOchange in Peak VO22 between the treatment and control between the treatment and control group during cardiopulmonary exercise testing.group during cardiopulmonary exercise testing.

No improvement in other objective parameters including No improvement in other objective parameters including 6-minute walk test, LV reverse remodeling, and 6-minute walk test, LV reverse remodeling, and secondary endpoint - quality of life score .secondary endpoint - quality of life score .

Conclusion:RethinQConclusion:RethinQ CRT did not improve Peak VOCRT did not improve Peak VO22 during exercise in patients with NYHA during exercise in patients with NYHA

Class III heart failure, QRS duration <130ms, EF ≤ 35% and Class III heart failure, QRS duration <130ms, EF ≤ 35% and mechanical dyssynchrony as specified in this trial. mechanical dyssynchrony as specified in this trial.

While there was a statistically significant improvement of NYHA class, While there was a statistically significant improvement of NYHA class, a secondary endpoint, there was no improvement in quality-of-life, 6-a secondary endpoint, there was no improvement in quality-of-life, 6-minute walking test, or echocardiographic measures of reverse LV minute walking test, or echocardiographic measures of reverse LV remodelingremodeling

A subgroup of patients with QRS duration between A subgroup of patients with QRS duration between 120 ms and 130 ms demonstrated an improvement from CRT, however 120 ms and 130 ms demonstrated an improvement from CRT, however

patients with QRS duration < 120 ms did not demonstrate improvementpatients with QRS duration < 120 ms did not demonstrate improvement

The subgroup of patients stratified on the basis of cardiomyopathy The subgroup of patients stratified on the basis of cardiomyopathy etiology did not demonstrate an improvement in peak VO2.etiology did not demonstrate an improvement in peak VO2.

PROSPECT TRIAL 5/2008PROSPECT TRIAL 5/2008

Predictors of response to CRTPredictors of response to CRT 53 centers worldwide, 426 patients53 centers worldwide, 426 patients Patients had standard CRT indications (OMT, Patients had standard CRT indications (OMT,

EF < 35%, Class III-IV, QRS > 130)EF < 35%, Class III-IV, QRS > 130) 12 ECHO parameters of dyssynchrony 12 ECHO parameters of dyssynchrony 69% of patients clinically improved and 56% 69% of patients clinically improved and 56%

showed a decrease in LVESV of >15%showed a decrease in LVESV of >15% No single ECHO measure of dyssynchrony No single ECHO measure of dyssynchrony

could help select responders to CRTcould help select responders to CRT

RAO is best to

distinguish BASE

position from APEX

BASE

APEX

Posterior

Anterior

LAO is best to

distinguishLATERAL

position from

SEPTAL

ANTERIOR

INFERIOR

LATERAL

SEPTAL

Anterior

PosteriorLateral

LAOLAO

The 3 levels of DyssynchronyThe 3 levels of Dyssynchrony

1.1. IntraventricularIntraventricular dyssynchrony is best treated dyssynchrony is best treated by by placing the LV lead in the best anatomicplacing the LV lead in the best anatomic locationlocation-usually the lateral or posterolateral -usually the lateral or posterolateral (proven my multiple studies). Get the LV (proven my multiple studies). Get the LV working.working.

2.2. InterventricularInterventricular dyssynchrony is dealt with by dyssynchrony is dealt with by adjusting the adjusting the V-VV-V interval. Get the RV and the interval. Get the RV and the LV to work together.LV to work together.

3.3. A-V A-V dyssynchrony is dealt with by adjusting dyssynchrony is dealt with by adjusting the the A-VA-V interval. Get the atria and the interval. Get the atria and the ventricles working together.ventricles working together.

Change in LVEF [%]

2%

9%

0%

2%

4%

6%

8%

10%P=0.04

-9.2

-28.4

-30

-25

-20

-15

-10

-5

0

P=0.04

Change in LV End-systolic Volume [ml]

Imp

rov

em

en

t

Posterolateral or Lateral walls are the best with Posterolateral or Lateral walls are the best with LBBB where the septum contracts first and then the LBBB where the septum contracts first and then the

lateral wall last.lateral wall last.

Paced at any other LV site

Paced at most mechanically delayed LV site

CRT and Tissue Doppler Imaging -a measure of CRT and Tissue Doppler Imaging -a measure of intraventricular delayintraventricular delay

• Measures dyssynchronous (delayed) contraction patterns @ different areas of the ventricle•Measure from the onset of the QRS to the peak systolic shortening of that segment•Defined as a segment with > 50 ms delay: this indicates intraventricular delay or asynchrony by ECHO criteria

•Colors: green-yellow-red (the longest delay of >300 ms)

V-V Timing: synchronize the RV V-V Timing: synchronize the RV and the LVand the LV

The best V-V setting by measuring the RVOT and LVOT The best V-V setting by measuring the RVOT and LVOT via PW Dopplervia PW Doppler

V-V above > 40 ms is considered abnormalV-V above > 40 ms is considered abnormal

In normalsIn normals, the RV will contract before the LV in the , the RV will contract before the LV in the heart by -20 msheart by -20 ms

LV and RV have different outputs in the newer devices LV and RV have different outputs in the newer devices that allow that allow sequentialsequential instead of instead of simultaneoussimultaneous delivery delivery of output and thus allow for this to be programmable.of output and thus allow for this to be programmable.

AV Delay Optimization MethodsAV Delay Optimization Methods

1.1. ElectrocardiographicElectrocardiographicCOMPANION trial methodCOMPANION trial method

2.2. Echocardiographic (combined)Echocardiographic (combined)Aortic velocity time integral (VTI) methodsAortic velocity time integral (VTI) methodsMitral velocity Doppler methods:E and A wavesMitral velocity Doppler methods:E and A wavesRitter formulaRitter formula

3.3. Hemodynamic measurements Hemodynamic measurements Pulse pressure methodPulse pressure methoddP/dtdP/dtmaxmax method method

Cardiac Resynchronization Therapy in Patients With Cardiac Resynchronization Therapy in Patients With Severe Severe SystolicSystolic Heart Failure:2008 Guidelines Heart Failure:2008 Guidelines

For patients who have left ventricular ejection fraction For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and than or equal to 0.12 seconds, and sinus rhythmsinus rhythm, cardiac , cardiac resynchronization therapy (CRT) with or without an ICD resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart is indicated for the treatment of New York Heart Association (NYHA) functional Class III or ambulatory Association (NYHA) functional Class III or ambulatory Class IV heart failure symptoms on optimal Class IV heart failure symptoms on optimal recommended medical therapy. recommended medical therapy.

For patients who have LVEF less than or equal to 35%, a For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and QRS duration greater than or equal to 0.12 seconds, and AFAF, CRT with or without an ICD is reasonable for the , CRT with or without an ICD is reasonable for the treatment of NYHA functional Class III or ambulatory treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms on optimal Class IV heart failure symptoms on optimal recommended medical therapy. recommended medical therapy.

For patients with LVEF less than or equal to 35% with For patients with LVEF less than or equal to 35% with NYHA functional Class III or ambulatory Class IV NYHA functional Class III or ambulatory Class IV symptoms who are receiving optimal recommended symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable. ventricular pacing, CRT is reasonable.

I IIa IIb III

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII


Cardiac Resynchronization Therapy in Patients Cardiac Resynchronization Therapy in Patients With Severe With Severe SystolicSystolic Heart Failure : 2008 Heart Failure : 2008

GuidelinesGuidelines

For patients with LVEF less than or equal to 35% with For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are receiving NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and who are optimal recommended medical therapy and who are undergoing implantation of a permanent pacemaker undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent ventricular pacing, and/or ICD with anticipated frequent ventricular pacing, CRT may be considered. CRT may be considered.

CRT is not indicated for asymptomatic patients with CRT is not indicated for asymptomatic patients with reduced LVEF in the absence of other indications for reduced LVEF in the absence of other indications for pacing. pacing.

CRT is not indicated for patients whose functional status CRT is not indicated for patients whose functional status and life expectancy are limited predominantly by chronic and life expectancy are limited predominantly by chronic noncardiac conditions. noncardiac conditions.




Indications for ICD Therapy Indications for ICD Therapy

20082008

Implantable Cardioverter-Implantable Cardioverter-Defibrillators Defibrillators

ICD therapy is indicated in patients who are survivors of ICD therapy is indicated in patients who are survivors of cardiac arrest due to ventricular fibrillation or hemodynamically cardiac arrest due to ventricular fibrillation or hemodynamically unstable sustained VT after evaluation to define the cause of unstable sustained VT after evaluation to define the cause of the event and to exclude any completely reversible causes. the event and to exclude any completely reversible causes.

ICD therapy is indicated in patients with structural heart ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether disease and spontaneous sustained VT, whether hemodynamically stable or unstable. hemodynamically stable or unstable.

ICD therapy is indicated in patients with syncope of ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological significant sustained VT or VF induced at electrophysiological study. study.




All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.

ICD therapy is indicated in patients with LVEF less than or ICD therapy is indicated in patients with LVEF less than or equal to 35% due to prior MI who are at least 40 days post-equal to 35% due to prior MI who are at least 40 days post-MI and are in NYHA functional Class II or III. MI and are in NYHA functional Class II or III.

ICD therapy is indicated in patients with nonischemic DCM ICD therapy is indicated in patients with nonischemic DCM who have an LVEF less than or equal to 35% and who are who have an LVEF less than or equal to 35% and who are in NYHA functional Class II or III. in NYHA functional Class II or III.

ICD therapy is indicated in patients with LV dysfunction due ICD therapy is indicated in patients with LV dysfunction due to prior MI who are at least 40 days post-MI, have an LVEF to prior MI who are at least 40 days post-MI, have an LVEF less than or equal to 30%, and are in NYHA functional Class less than or equal to 30%, and are in NYHA functional Class I. I.

ICD therapy is indicated in patients with nonsustained VT ICD therapy is indicated in patients with nonsustained VT due to prior MI, LVEF less than or equal to 40%, and due to prior MI, LVEF less than or equal to 40%, and inducible VF or sustained VT at electrophysiological study. inducible VF or sustained VT at electrophysiological study.







ICD implantation is reasonable for patients with unexplained ICD implantation is reasonable for patients with unexplained syncope, significant LV dysfunction, and nonischemic DCM. syncope, significant LV dysfunction, and nonischemic DCM.

ICD implantation is reasonable for patients with sustained VT and ICD implantation is reasonable for patients with sustained VT and normal or near-normal ventricular function. normal or near-normal ventricular function.

ICD implantation is reasonable for patients with HCM who have 1 ICD implantation is reasonable for patients with HCM who have 1 or more majoror more major†† risk factors for SCD. risk factors for SCD.

ICD implantation is reasonable for the prevention of SCD in ICD implantation is reasonable for the prevention of SCD in patients with arrhythmogenic right ventricular patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) who have 1 or more risk dysplasia/cardiomyopathy (ARVD/C) who have 1 or more risk factors for SCD. factors for SCD.

ICD implantation is reasonable to reduce SCD in patients with long-ICD implantation is reasonable to reduce SCD in patients with long-QT syndrome who are experiencing syncope and/or VT while QT syndrome who are experiencing syncope and/or VT while receiving beta blockers.receiving beta blockers.

I IIaIIbIII


† See Section 3.2.4, “Hypertrophic Cardiomyopathy,” in the full-text guidelines for definition of major risk factors.

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII


ICD implantation is reasonable for nonhospitalized patients ICD implantation is reasonable for nonhospitalized patients awaiting transplantation. awaiting transplantation.

ICD implantation is reasonable for patients with Brugada ICD implantation is reasonable for patients with Brugada syndrome who have had syncope. syndrome who have had syncope.

ICD implantation is reasonable for patients with Brugada ICD implantation is reasonable for patients with Brugada syndrome who have documented VT that has not resulted in syndrome who have documented VT that has not resulted in cardiac arrest. cardiac arrest.

ICD implantation is reasonable for patients with ICD implantation is reasonable for patients with catecholaminergic polymorphic VT who have syncope and/or catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta blockers. documented sustained VT while receiving beta blockers.

ICD implantation is reasonable for patients with cardiac ICD implantation is reasonable for patients with cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. sarcoidosis, giant cell myocarditis, or Chagas disease.

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII



ICD therapy may be considered in patients with nonischemic ICD therapy may be considered in patients with nonischemic heart disease who have an LVEF of less than or equal to 35% heart disease who have an LVEF of less than or equal to 35% and who are in NYHA functional Class I. and who are in NYHA functional Class I.

ICD therapy may be considered for patients with long-QT ICD therapy may be considered for patients with long-QT syndrome and risk factors for SCD. syndrome and risk factors for SCD.

ICD therapy may be considered in patients with syncope and ICD therapy may be considered in patients with syncope and advanced structural heart disease in whom thorough invasive advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to define a cause. and noninvasive investigations have failed to define a cause.

ICD therapy may be considered in patients with a familial ICD therapy may be considered in patients with a familial cardiomyopathy associated with sudden death. cardiomyopathy associated with sudden death.

ICD therapy may be considered in patients with LV ICD therapy may be considered in patients with LV noncompaction. noncompaction.

III IIaIIaIIa IIbIIbIIbIIIIIIIIIIII IIaIIaIIa IIbIIbIIbIIIIIIIIIIII IIaIIaIIa IIbIIbIIbIIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII

I IIaIIbIII



ICD therapy is not indicated for patients who do not have a ICD therapy is not indicated for patients who do not have a reasonable expectation of survival with an acceptable reasonable expectation of survival with an acceptable functional status for at least 1 year, even if they meet ICD functional status for at least 1 year, even if they meet ICD implantation criteria specified in the Class I, IIa, and IIb implantation criteria specified in the Class I, IIa, and IIb recommendations above. recommendations above.

ICD therapy is not indicated for patients with incessant VT or ICD therapy is not indicated for patients with incessant VT or VF. VF.

ICD therapy is not indicated in patients with significant ICD therapy is not indicated in patients with significant psychiatric illnesses that may be aggravated by device psychiatric illnesses that may be aggravated by device implantation or that may preclude systematic follow-up. implantation or that may preclude systematic follow-up.

ICD therapy is not indicated for NYHA Class IV patients with ICD therapy is not indicated for NYHA Class IV patients with drug-refractory congestive heart failure who are not drug-refractory congestive heart failure who are not candidates for cardiac transplantation or cardiac candidates for cardiac transplantation or cardiac resynchronization therapy defibrillators (CRT-D). resynchronization therapy defibrillators (CRT-D).







ICD therapy is not indicated for syncope of undetermined ICD therapy is not indicated for syncope of undetermined cause in a patient without inducible ventricular cause in a patient without inducible ventricular tachyarrhythmias and without structural heart disease. tachyarrhythmias and without structural heart disease.

ICD therapy is not indicated when VF or VT is amenable ICD therapy is not indicated when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias to surgical or catheter ablation (e.g., atrial arrhythmias associated with the Wolff-Parkinson-White syndrome, RV associated with the Wolff-Parkinson-White syndrome, RV or LV outflow tract VT, idiopathic VT, or fascicular VT in or LV outflow tract VT, idiopathic VT, or fascicular VT in the absence of structural heart disease). the absence of structural heart disease).

ICD therapy is not indicated for patients with ventricular ICD therapy is not indicated for patients with ventricular tachyarrhythmias due to a completely reversible disorder tachyarrhythmias due to a completely reversible disorder in the absence of structural heart disease (e.g., in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, or trauma). electrolyte imbalance, drugs, or trauma).






SummarySummary

Large number of patients studied in multiple Large number of patients studied in multiple RCTs.RCTs.

CRT improves quality of life, exercise capacity, CRT improves quality of life, exercise capacity, functional capacity, EF, peak VO2.functional capacity, EF, peak VO2.

CRT reduces the risk of mortality, worsening HF, CRT reduces the risk of mortality, worsening HF, and hospitalizations for CHF.and hospitalizations for CHF.

CRT + ICD significantly reduces risk of mortality.CRT + ICD significantly reduces risk of mortality.

device therapy in heart failure teresa m. menendez hood, m.d., f.a.c.c

Documents

heart failure slide

class mortality

lv pacing

hf patients

heart failure morbidity

heart failure teresa

heart failure background

sudden mortality