2006 orvieto, giornate cardoilogiche orvietane. il trattamento non farmacologico dello scompenso...

Giornate Cardiologiche OrvietaneGiornate Cardiologiche OrvietaneIl trattamento non farmacologico dello Il trattamento non farmacologico dello

SCOMPENSO CARDIACOSCOMPENSO CARDIACOStefano Nardi, MD, PhD

AZIENDA OSPEDALIERA SANTA MARIA TERNI AZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLARE DIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA

STRUTTURA SEMPLICE DI ARITMOLOGIA STRUTTURA SEMPLICE DI ARITMOLOGIA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE

CHFCHF: non pharmacological approach: non pharmacological approach

Reduced Mortality in HFACE-I & Beta Blockade

Reduce Mortality

11.5%

15.6%12.4%

7.8%

0%4%8%

12%16%

SOLVD-T MERIT-HF+ CIBIS II

1 Ye

ar M

orta

lity

Placebo Treatment


Digossina, Diuretici, Idralazina ACE-I

ß-blocker and ACE-I

SOLVD CONCENSUS da -16 a -31% CIBIS II

COPERNICUS - 35%

Mortalità

Mortality Mortality

too Hightoo High

Mortalità ad 1 annoITALIAN NETWORK CHF

4,1 %4,1 %

11,7 %11,7 %

24,8 %24,8 %

36,7 %36,7 %

15,1 %15,1 %

(%)(%)

NYHA I1

NYHA II2,14

[1,33-3,44]

NYHA III3,77

[2,32-6,12]

NYHA IV5,54

[3,23-9,48]

TotaleRischio Relativo

• 600.000 CHF pts• 87.000 morti / anno• Mortalità a 5 anni >70%• 44% CHF re-hospitalization

a 6 mesi dal primo evento• % della spesa sanitaria per

CHF: 1,5 - 2% • CHF prima causa di

ospedalizzazione nella popolazione > 65 anni di età

• CHF prima patologia per durata della degenza ospedaliera

1 Framingham Heart Study (‘48 – ‘88) in Atlas of Heart Diseases.2 AHA. Heart Disease and Stroke Statistics—’03 Update.

CHF Patients Survival Results1CHF Patients Survival Results1


a Vicious Cycle

Abnormal RV-LV sequence

Mitral Regurgitation

Segmental Dyskinesia

Dysynchronous Contraction

Abnormal LV activation sequence

↑ Neurohormones

↓ LVEF

Dissynchrony RV/LV

filling flow


Burkhoff D, Am J Phys ‘87

Different Pacing-site in CANINE model

What does it mean What does it mean Asynchronus activation ? Asynchronus activation ?


http://circ.ahajournals.org/content/vol94/issue4/images/large/0030f2.jpeg

http://ajpheart.physiology.org/content/vol285/issue5/images/large/h41132622005.jpeg

Spragg DD, Circulation ’03

Regional Alterations of Protein Expression in CHF dogs


http://circ.ahajournals.org/content/vol108/issue8/images/large/16FF1.jpeg

http://circres.ahajournals.org/content/vol96/issue5/images/large/1FF1.jpeg

SinusSinusnodenode

AVAVnodenode

BundleBundlebranch orbranch or

diffuse blockdiffuse block

Delayed conductionDelayed conduction

• Abnormal RV-LV sequence• Abnormal LV activation

sequence• Segmentary dyskinesia• Aggravation of mitral

regurgitation• Disynchrony of RV and LV

filling flows

Dyssynchrony Ventricular ContractionDyssynchrony Ventricular Contraction

What is abnormal in the HF pts?What is abnormal in the HF pts?• Delayed AV sequence• Mitral regurgitation• Decreased filling time


What does it means DYSSYNCHRONYSM ?

0

5

10

15

20

25

301 Year-Mortality

Total Sudden Death

LBBBNo LBBB

Study pop

11.9

16.1

10.5

5.5 4.97.3

p<0.001

p<0.001

60%

70%

80%

90%

100%

0 60 120 180 240 300 360Days in Trial

Cu

mu

lati

ve S

urv

ival

QRS Duration (msec)

<9090-120

120-170170-220

>220

Adapted from Gottipaty et al. JACC 1999; 33(2):145A (abstract 847-4)

INCHF

• VEST study analysis• NYHA Class II – IV pz


Di Donato M, Circulation ‘04

Which is the relationship between Dysshynchronysm and QRS duration ?

60%

70%

80%

90%

100%

0 60 120 180 240 300 360Days in Trial

Cu

mu

lati

ve

Su

rv

iva

l

Ole-A. Breithardt, MD

ALTERED WORK-LOAD


• Radionuclide • MRI • ECHO-cardiography

Which technique for Patients selection ??

INTER-VCD (CARE HF) Conventional Echo-Doppler (Q-efflux Ao –Q-efflux Po >40 ms)

INTRA-VCD M-mode (validate only in QRS wide) PW-TDI Strain Rate Echo 3D


• Optimizes AV contraction sequence

• Reduces pre-systolic mitral regurgitation

• Improves atrial preloading of the ventricle

• Increases filling time

Mechanism IMechanism IAtrio-Ventricular SynchronyAtrio-Ventricular Synchrony

Rationale for CRTRationale for CRT What does pacing changeWhat does pacing change??


• Optimizes ventricular activation• Increases pumping effectiveness• Reduces regional wall stress (WMSI)• Decreases mitral regurgitation• Resynchronizes ventricular filling flows• Decreases filling pressures

Mechanism IIMechanism IIVentricular CoordinationVentricular Coordination

Rationale for CRTRationale for CRT What does pacing changeWhat does pacing change??


OAVD Restores AV Synchrony

PP RR

INTRINSICINTRINSICAorticAortic

pressurepressure

LVLVpressurepressure

PPPP

PeakPeakatrial systoleatrial systole

Start ofStart ofLV systoleLV systole

DiastolicMitral

Regurgitation

MaximumEffective Preload

PP VV

PACEDPACEDPPPP

SynchronizedSynchronizedLV and atrialLV and atrial

systolessystoles

Auricchio, PACE `98


Kass et al, Kass et al, Circulation 99Circulation 99

IntrinsicIntrinsicPacedPaced

00 100100 200200 30030000

4040

8080

120120RV SeptumRV Septum

00 100100 200200 30030000

4040

8080

120120BiventricularBiventricular

00 100100 200200 30030000

4040

8080

120120RV ApexRV Apex

00 100100 200200 30030000

4040

8080

120120LV FreewallLV Freewall

LV Volume LV Volume (mL)(mL)

LV P

ress

ure

LV P

ress

ure

(mm

Hg)

(mm

Hg)

LV P

ress

ure

LV P

ress

ure

(mm

Hg)

(mm

Hg)

LV Volume LV Volume (mL)(mL)

Acute studiesCHFCHF: non pharmacological approach: non pharmacological approach

Cumulative Enrollment in C.R. Cumulative Enrollment in C.R. Randomized TrialsRandomized Trials

0

1000

2000

3000

4000

1999 2001 2003 2005

Result s Present ed

Cum

ulat

ive

Pati

ents

PATH CHF

MUSTIC SRMUSTIC AF

MIRACLE

CONTAK CD

MIRACLE ICD

PATH CHF II

COMPANION

MIRACLE ICD II

CARE HF

DOUG SMITHDOUG SMITH


Auricchio et al., NASPE ‘99

PATH-CHF: Inclusion Criteria (42 pts)

• Dilated cardiomyopathy of any etiology• NYHA Class III (> 6 months) or NYHA IV• Optimal individual drug therapy • QRS duration >120 msec • PR Interval >150 msec• Sinus rate > 55 bpm• No conventional pacemaker indication

PATH CHF


325

350

375

400

425

450

475

pre-implantn=20

4 weeksn=20

8 weeksn=20

12 weeksn=20

6 monthsn=20

12 monthsn=20

Meter

s

Long Term Benefit PATH CHF


0

10

20

30

40

50

60

pre-implantn=20

4 weeksn=20

8 weeksn=20

12 weeksn=20

6 monthsn=20

8 monthsn=20

10 monthsn=20

12 monthsn=20

Minnes

ota Sc

ore

Quality of Life6 - MWT


Long Term Benefit: Peak Oxygen Uptake

0.9

1

1.1

1.2

1.3

1.4

0 1 2 3 4 5 6 7 8 9 101112

Months

Peak

VO2

(l/min)

PATH CHF


0

10

20

30

40

days

of

hosp

italiz

ation

1 Year1 YearPre-ImplantPre-Implant

1 Year1 YearPost-ImplantPost-Implant

P P == .003 .003


MIRACLE Inclusion Criteria (571 pts)

• Moderate or severe HF (NYHA III-IV)• Stable optimal HF medical therapy regimen

for >1month - Diuretics (93-94%) - ACE-I or ARB (90-93%) if tollerated - β-blocker (55-62%) at stable regimen for>3 months

• QRS duration ≥150 msec • LVEF ≤35% or LVEDD ≥55mm (echo measure)• Sinus rate > 55 bpm • 6 MWT <450m

Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853


Benefits Sustained Through 2 yr: MIRACLE Study Program

0100200300400500

Mean 6-MWT(m)

1

2

3

4

020406080

100

6 (N=1124) 12 (N=693) 18 (N=320) 24 (N=68)

Months of Active CRT

Mean NYHAFunctional Class

Mean QoL Score Improvement ↓

Baseline Follow-up

PairedDataDisplayed

P<0.001 P<0.001 P<0.001 P=0.01

P<0.001 P<0.001 P<0.001 P<0.001

P<0.001 P<0.001 P<0.001 P<0.001

Source: Abraham, WT et al. AHA 2003


Change in MR Jet AreaChange in MR Jet Area

-4-4-3-3-2-2-1-10011

ControlControl(n=118)(n=118)

CRTCRT(n=116)(n=116)

cmcm22

P<0.001P<0.001 P=0.009P=0.009

Change in LVEDDChange in LVEDD

-6-6

-4-4

-2-2

00

22



mmmm P<0.001P<0.001

Absolute Change in LVEFAbsolute Change in LVEF

-2-2

00

22

44

66

88



%%

Baseline (mm)Baseline (mm)69 ± 10

70 ± 10Baseline (cmBaseline (cm 2)

7.2 ± 4.9

7.6 ± 6.4Baseline (%)Baseline (%)

22 ± 6

22 ± 6

Paired median change from baseline at 6 months

Cardiac Function and StructureMIRACLE


Effects on Cardiac Function and Oxidative Stress

0,14

0,16

0,18

0,20

0,22

0,24

500 600 700 800 900

dP/ dt max ( mm/ Hg/ s)

MVO

2/HR

(Rel

ative

Unit

s) Dobutamin

LV Pacing

P< 0.05

Nelson et al. Circulation 2000

Myocardial Oxidative Metabolism

0

0,02

0,04

0,06

LV RV

k mon

o(min

-1)

p=0.86

p=0.62

n=8

Myocardial Efficiency Work Metabolic Index

0

2

4

6

8

10

12

mm

HG

·L·m

-2

Baseline CRT

p =0.024

Ukkonen et al. Circulation 2003

n=7

MIRACLE


Mortality/Morbidity from Published Randomized, Controlled Trials

Risk reduction with CRT

Study (n random.) FU

Mor-tality & Hosp.

Mortal. & HF Hosp.

Mor-tality

HF Mort.

HF Hosp.

MIRACLE (n=453)

6 Mo NR 39%* 27% NR 50%*

MIRACLE ICD (n=369)

6 Mo 2% 0% 0% NR NR

Contak CD (n=490)

3-6 Mo NR NR 30% NR 18%

Meta-analysis (n=1634)

3-6 Mo NR NR 23% 51%* 29%*

* P < 0.05


RandomizeRandomize1:2:21:2:2

• Optimal Optimal Pharmacologic Pharmacologic Therapy (OPT)Therapy (OPT)

• OPTOPT

• BV pacingBV pacing +

• OPTOPT

• BV pacingBV pacing

• DefibrillationDefibrillation

+

CoComparison of mparison of MMedical Therapy, edical Therapy, PPacing acing anand d DefibrillatDefibrillationion in Chronic Heart Failure in Chronic Heart Failure ((COMPANIONCOMPANION))


COMPANION CARE - HF

Cleland J. G.F, NEJM ‘05Bristow, NEJM ‘04


• Reduced LVEF remains the single most important risk factor for overall mortality and SCD.1

• Increased risk is measurable at EF above 30%, but an EF ≤30% is the single most powerful independent predictor for SCD.2

1Prior SG, Aliot E, Blonstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J, Vol. 22; 16; August 2001.2 Myerburg RJ, Castellanos A. Cardiac Arrest and Sudden Cardiac Death, in Braunwald E, Zipes DP, Libby P, Heart Disease, A textbook of Cardiovascular Medicine. 6th ed. 2001. W.B. Saunders, Co., p. 895.

Relationship of SCD Relationship of SCD and LV Dysfunctionand LV Dysfunction


Several RANDOMIZED studies have demonstrated that ICD reduce MORTALITY (~30-50%), both in primary and in secondary prevention


• 126 pts underwent CRT • If criteria for ICD

(US guidelines, including MADIT) CRT-D

• If no, CRT-P

CRT-D vs CRT-P in Severe LV dysf. Ermis et al. JCE, ‘04

Miglioramento del 41% (p =0,01)

I pazienti che non presentano rischi noti di Morte Improvvisa li sviluppano col passare del tempo …ecco perché necessitano di un ICD di back-up


Mortalità totale

Frazione di eiezione

Morte per causa aritmica

Diss. E-M ElettricaInfettiva

NeoplasticaNeurologica

Ecc. All’aumentare della LVEF si riduce la mortalità per CHF ma aumenta quella per causa aritmica

Challenges in electrical management of CHF

NYHA II

Other24%

CHF12%

Sudden death64%

N=103

NYHA III

Sudden death59%

CHF26%

Other15%

N=232

NYHA IV

Sudden death33%

CHF56%

Other11%

N=27 MERIT-HF


ACE-I & Beta Blockade Reduce Mortality

11,5%

15,6%12,4%

7,8%

0%4%8%

12%16%

SOLVD-T MERIT-HF+ CIBIS II

1 Ye

ar M

orta

lity

Placebo Treatment

Further Reduction with CRT + ICD

for Higher Risk PatientsHF

Mortality

SuddenCardiac Death

CRT

ICD

Weight of Evidence: CRT


Digossina, Diuretici, Idralazina ACE-I

ß-blocker and ACE-I ß-blocker,

ACE-I and CRT-D

COMPANION - 36%

SOLVD CONCENSUS da -16 a -31% CIBIS II

COPERNICUS - 35%

Mortalità

CONCLUSIONSCONCLUSIONS


D’Ascia C, Eu Heart J ‘06

CRT

Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk

100

125

150

175

200

225

**

*

*

†

* *

*

†

Left

ven

tric

ular

vol

ume

(mL) *

VO2

(ml/

min

/mVO

2 (m

l/m

in/m

22 ))

DODO22 (ml/min/m (ml/min/m22))

Critical DOCritical DO2 2

DISOXIADISOXIA

Critical VOCritical VO22

NormalNormal

ReverseRemodelling

TNF-alpha expressionApoptosisFibrosis


2002 Classe IIa: Symptomatic pts, Class NYHA III or IV, DCM (hydiopatic or ischemic) prolonged QRS interval (≥ 130 ms), LVEDD≥ 55 mm, LVEF ≤ 35%.

News 2005Classe I:Symptomatic pts, Class NYHAIII, Synus Rhythm, OMT forCHF, Dyssynchrony

(Level of Evidence A)

Aggiornamento delle linee guida ACC/AHA (2002 2005) →

Terapia CRT


ESC 2005 Classe IIa: Symptomatic pts in NYHA Class III or IV in OMT for CHF, Dyssinchrony and reduced LVEF

ACC/AHA 2005Classe I:Symptomatic pts, Class NYHAIII, Synus Rhythm, OMT forCHF, Dyssynchrony

(Level of Evidence A)

Confronto tra LINEE GUIDA ESC e ACC/AHA (2005)

Terapia CRT

CRT for improve symptoms and CHF-H (Level of Evidence A)

CRT for improve risk of death (Level of Evidence B)


CLASS I SR, LVEF ≤ 35%, QRS > 120ms, NYHA III-IV, OMT

CLASS II

Atiral Fibrillation LVEF ≤ 35%, QRS > 120ms, NYHA III-IV in OMT LVEF ≤ 35%, QRS ≤ 120 ms, NYHA III-IV, OMT Dysshynchronism (Echo), SR, LVEF ≤ 35%, QRS > 120msSymptomatic NYHA class II, PM or ICD indication (in primary prevention) Chronic RVA pacing, LVEF ≤ 35%, NYHA III-IV, OMT, Severe Dyssynchronism (Up-grading),

LINEE GUIDA AIAC 2006CRT


High anatomic of CS system

Optimization of CRT

(n° vene, presenza di valvole, angolature,

tortuosità ecc.)


• Reduction of responsivity in ischemic disease (SCAR, Non contractile segment etc) (Gasparini M, PACE ’03)

• In Ischemic DCM the asynchronysm can interest each LV wall, whereas CRT is more efficacy in lateral or postero-lateral wall (Yu CM, Circulation ‘04)

• Pacing not efficacy• Comorbidity• Severe CHF or hemodinamic

instability

Why are the Non-Responders ?CHFCHF: non pharmacological approach: non pharmacological approach

• No MR (Reuter S et a. Am J Cardiol ‘02) or severe MR (Achilli A, Italian Heart J ‘04)

• Elevated LVEDV and LVESV (Bax JJ, JACC ‘04)

• Permanent AFib - controverso: ablazione NAV? Speranza di recupero RS con riduz. IM e reverse LV remodeling?

• Class NYHA IV

Why are the Non-Responders ?CHFCHF: non pharmacological approach: non pharmacological approach

CHF Population

6.5 Mio

NYHA III + IV (30 - 35%)

1.95 Mio

Wide QRS (10 - 30%)

Resynchronization Rx Target Population:195’000

650’000

Incidence = 580’000 (9.0%)Mortality = 300’000 (4.6%)

CHF Population in EuropeCHF Population in EuropeCHFCHF: non pharmacological approach: non pharmacological approach

Relative Cost of CRTCost per pat ient

$0$20$40$60

CRT+ I CD

CRT

Hip/ knee replace

PTCA

CABG

Dialysis

$ t housands

Total Annual Expenditures

$0 $5 $10 $15 $20

$ BillionsDoug Smith:

Doug Smith:

CONCLUSIONSCONCLUSIONS


0

5000

10000

15000

Baseline Post-implant

Intensive careCardiologyOthers

Patient Cost Baseline: 12,784 Euro Patient Cost (Implant included): 12,362 EuroPatient Cost Post-implant: 1,680 Euro

Hospital costs per patient

Cost EffectivenessAnalysis of Biventricular Pacing in HF

Curnis A 2001

CONCLUSIONSCONCLUSIONSCHFCHF: non pharmacological approach: non pharmacological approach

Creating Realistic patients expectations

• Approximately two-third of patients should experience improvement, but some patients may not experience immediate improvement

• Have patients set their own goals of what they would like to do following CRT: Grocery shopping, Decreasing Lasix dose, Walking to the mailbox without stopping, Lying flat to sleep


Necessari ulteriori studi con “follow-up” a più lungo termine per capire il giusto

“LINK” esistente tra efficacia in ACUTO, mantenimento del risultato in cronico e

CONSEGUIMENTO DEGLI “END POINT”

Perfezionare le conoscenze sui meccanismi della CHF

Migliorare la tecnologia, rendere le procedure sempre più fattibili

minimizzando i rischi


GRAZIE PER LA GRAZIE PER LA CORTESECORTESE

ATTENZIONEATTENZIONE


• Have patients set their own goals of what they would like to do following CRT: Grocery shopping, Decreasing Lasix dose Walking to the mailbox without stopping, Lying flat to sleep

• Encourage them to be part of the group that responds to their therapy

Creating Realistic expectations

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

DEPOSITODEPOSITO

InSync Italian Registry

QRS duration (msec) 172+32Ejection fraction (%) 25+7LV end Diast. Diameter (mm) 71+9NYHA functional class 3,15+0,616 min walking test (m) 269+142Chronic Atrial Fibrillation 17,4%

190 patients M= 82,8%; Age= 68+ 8ETIOLOGY: Ischemic 46,6%; Idiopatic 37,9%; Other 15,5%

InSyncItalianRegistry



M. Zardini et al, Eur Hear 2000

LVEF %

0

10

20

30

40

BASELINE FOLLOW-UP

%

6m HWT

0

100

200

300

400

500

BASELINE FOLLOW-UP

m

NYHA class

0

1

2

3

4

BASELINE FOLLOW-UP

QOL Score

0

10

20

30

40

50

60

70

80

BASELINE FOLLOW-UP

p < .0001

p < .0001 p < .0001

p < .0001

Clinical Outcome


Results Active pacing

Inactivepacing

p

6-min w (m) 399 ± 100 326 ± 134 .0001QOL score 29.6 ± 21.3 43.2 ± 22.8 .0002VO2 (ml/min/Kg) 16.2 ± 4.7 15 ± 4.9 0.02

S.Cazeau et al NEJM 2001;344:873-80S.Cazeau et al NEJM 2001;344:873-80

MUSTIC Results (67 pts)


VO2

(ml/

min

/mVO

2 (m

l/m

in/m

22 ))


OO22ERER


DISOXIADISOXIA


DODO22 = = QQC C X CaX CaOO22

VOVO22 = = DODO2 2 X X OO22ERER

NormalNormal

DODO22 = =QQC C x (1,34 xx (1,34 x Hb x Sa Hb x SaOO22) x 10) x 10


QOL & Functional Capacity 6 Months in Moderate to Severe HF

-20-15-10-50

P<0.001 P=0.02 P=0.017P<0.001

QoL Score(MLWHF)

Avg. Change

0%20%40%60%80%

MIRACLE MUSTIC SR MIRACLE ICD Contak CD

P<0.001 P=0.006P=0.007

Data sources:MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59

Control CRT

NYHA ClassProportionChanging 1

or more Classes

Improve. ↓

Not Reported


Exercise Capacity 6 Months in Moderate to Severe HF

-20

0

20

40

60 P<0.001 P=0.36 P=0.029P<0.001

6 Min WalkAvg. Change

(m)

000

1

2

3

MIRACLE MUSTIC SR MIRACLE ICD Contak CD

P<0.001

P=0.029

P=0.04P=0.003

Data sources:MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59

Control CRT

Peak VO2

Avg. Change (mL/kg/min)


Effect on LV Structure Effect on LV Structure 6 Months in Moderate to Severe HF

-40

-20

0

P<0.001P=0.06

LVEDVAvg. Change

(mL)

-6-4-202

MIRACLE MIRACLE ICD Contak CD

P<0.05 P=0.81 P=0.001

Control CRT

LVEDDAvg. Change

(mm)

NOT REPORTED

Data sources: MIRACLE: Circulation 2003MIRACLE ICD:JAMA 2003CONTAK CD: J Am Coll Cardiol 2003


0

2

4

6

P<0.001P=0.12

P=0.029

LVEFAvg. Change(Absolute %)

-3-2-10

MIRACLE MIRACLE ICD Contak CDP<0.001

P=0.58

Data sources: MIRACLE: Circulation 2003MIRACLE ICD:JAMA 2003CONTAK CD: J Am Coll Cardiol 2003 Control CRT

MR Jet AreaAvg. Change

(cm2)

Not Reported

Effect on LV Function Effect on LV Function 6 Months in Moderate to Severe HF


CRT Does Not Promote Ventricular Arrhythmias

• Analyzed 1,044 patients with ICDs from 2 trials:– CONTAK CD– MIRACLE ICD

• Odds ratio (CI):0.92 (0.67 – 1.27)

Patients with VT or VF during Follow-up

17,2%18,4%

No CRT CRT

Prop

orti

on

Bradley DJ, et al. JAMA 2003


Left Ventricular End Systolic Diameter

200

250

300

350

400cm3

Base 6 Mo

P=0.01

CRT Promotes Reverse Remodeling in Class II CHF

Left Ventricular End Diastolic Diameter

200

250

300

350

400cm3

Base 6 Mo

P=0.04

Left Ventricular Ejection Fraction

20

22

24

26

28

30%

Base 6 Mo

P=0.02

• Control (n=85) ♦ CRT (n=69)

MIRACLE ICD II


• Radionuclidi • RMN • ECOcardiografia

Patients selectionCardiac Resynchronization TherapyCardiac Resynchronization Therapy

INTER-VCD Eco-Doppler convenzionale (Q-efflusso Ao –Q-efflusso Po >40 msec)

INTRA-VCD Eco M-mode (validate only in QRS wide) PW-TDI Strain Rate Echo 3D

Quando isolata, BASSO VALORE PREDITTIVO

DCM - Ischemic

Advanced age

NYHA Class IV

PeAF No MR

Maggiori LVEDV LVESV

Cardiac Resynchronization TherapyCardiac Resynchronization TherapyWhy are the Non-Responders ?

Cardiac Resynchronization TherapyCardiac Resynchronization TherapyRelated Risks

Complicat ions ( 1)

4,8

3,7

1,5

1,0

1,8

0,3

10,6

10,0

2,3

2,4

1,7

0,3

0 5 10 15

Unsucess. Implant

LV Lead

Coronary Sinus

Infection

30 day mortality

Procedure death

Percent of Pat ient s

MIRACLE+CONTAKCD+MIRACLE ICD

InSync III/Attain4193

Reduced Procedure Time w it h I ncreased Exper ience (2)

60

120

180

240

300

Up t o f ir st5

Next 6 t o10

Next 11more

Cent er-based exper ienceIm

plan

t Ti

me

(min

utes

) P < 0.001

Study Period AttemptsPrimary LV Lead

MIRACLE 11/98 – 12/00 591 Attain 2187

Contak CD 2/98 – 12/00 517 EasyTrak

MIRACLE ICD 10/99 – 8/01 636 Attain 4189

InSync III 11/00 – 6/02 334 Attain 4193

1. Greenberg, et al. PACE 2003;26(4p2): 952 (Abstract 93)

2. Unpublished data. Medtronic. Inc.

Relazione di Frank-Starling

P intraventric. (mmHg)

= sviluppo di forza

50

100

150

200

250

50 100 150 200 250

Volume ventricolare sinistro (ml)= lunghezza iniziale della fibra miocardica

sistole

diastole

Definizione: entro limiti fisiologici, tanto più il cuore si riempie durante la diastole, tanto maggiore sarà la quantità di sangue pompata in aorta in sistole


1 Framingham Heart Study (1948 – 1988) in Atlas of Heart Diseases.2 American Heart Association. Heart Disease and Stroke Statistics—2003 Update.

CHF Patients Survival ResultsCHF Patients Survival Results11

1009080

70

605040

3020100

Prob

abili

ty o

f su

rviv

al, %

Men (Men (n n = 237)= 237)Women (Women (nn = 230) = 230)

Time after CHF diagnosis, years0 2 4 6 8 10

80% of men and 70% of women who have CHF will die within 8

years.2


years.2


NYHA CLASS

Ann

ual s

urvi

val (

%)

Hos

pita

lizat

ions

/ y

ear

100

75

50

25

0I II III IV

1

10Survival

Hospitalization

.1

Hospitalization / NYHA-classCardiac Resynchronization TherapyCardiac Resynchronization Therapy

Volume Volume OverloadOverload

Pressure Pressure OverloadOverload

Loss of Loss of MyocardiumMyocardium

Impaired Impaired ContractilityContractility

LV Systolic DysfunctionEF < 35%

↓↓ Cardiac Cardiac OutputOutput

Hypoperfusion Hypoperfusion

↑↑ End Systolic Volume End Systolic Volume

↑↑ End Diastolic Volume End Diastolic Volume

Pulmonary Congestion Pulmonary Congestion

LV Systolic DysfunctionCardiac Resynchronization TherapyCardiac Resynchronization Therapy

Proposed Mechanisms of Benefit

IntraventricularSynchrony

AtrioventricularSynchrony

InterventricularSynchrony

↑ dP/dt, ↑ EF, ↑ CO(↑ Pulse Pressure) ↓ MR ↓ LA

Pressure↑ LV Diastolic

Filling↑ RV Stroke

Volume

↓ LVESV ↓ LVEDV

Reverse Remodeling

Cardiac Resynchronization

Yu CM, Circulation ‘02


QoL Overall perception of health

3645

554848

525658

70

Heart Failure NYHA Class IV

Heart Failure NYHA Class III

Heart Failure NYHA Class II

Chronic Bronchitis

Valve disease symptomatic

AF symptomatic

Angina

Depression

General population

Adjusted SF 36 means Hobbs FDR, et al. Eur Heart J 2002

Cardiac Resynchronization TherapyCardiac Resynchronization TherapyQuali sono le ragioni della CRT ?

LBBB

LABB +Incomplete LBBB

NO LBBB

25.2%

67.9.%

6.9%

0

2000

4000

6000

8000

5517

3476

1771

TOTAL POPULATION

NO LBBB

LBBB + LABB +imcomplete LBBB

n°

Prevalence of wide QRS and LBBB in the Study population (N°=5517)

INCHF


Completed 6-MonthCompleted 6-MonthFollow-upFollow-up(n = 201)(n = 201)

Completed 6-MonthCompleted 6-MonthFollow-upFollow-up(n = 215)(n = 215)

16 Death 122 Heart transplant 01 Infection/explant 15 Missed 6M FU 0

Control Control (n = 225)(n = 225)

CRT CRT (n = 228)(n = 228)

Randomized Randomized 6-Month Protocol6-Month Protocol

(n = 453)(n = 453)Enrollment & “Follow Up”


MIRACLE

Submaximal ExerciseDistance Walked in 6 MinutesDistance Walked in 6 Minutes Change from Baseline*Change from Baseline*

00

1010

2020

3030

4040

5050

6060

00 33 66

Follow-up Period (Month)Follow-up Period (Month)

Met

ers

Met

ers

11

P=0.004P=0.004P=0.003P=0.003

P=0.005P=0.005

Baseline (meters)Baseline (meters)291 ± 101

305 ± 85

CRTCRT

ControlControl


MIRACLE

Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853

QOL


Change from Baseline*Change from Baseline*

00

55

1010

1515

2020

2525

00 33 66Follow-up Period (Month)Follow-up Period (Month)

Sco

re I

mp

rove

men

t (p

oin

ts)

Sco

re I

mp

rove

men

t (p

oin

ts)

11

P=0.001P=0.001P<0.001P<0.001P<0.001P<0.001

CRTCRT

ControlControl

Minnesota Living with Heart Failure Questionnaire

Baseline (score)Baseline (score)

59 ± 21

59 ± 20

MIRACLE

NYHA Functional Class

00

2020

4040

6060

8080

100100

120120

Nu

mb

er o

f P

atie

nts

Nu

mb

er o

f P

atie

nts

Improved 2 orImproved 2 ormore classesmore classes

Improved 1Improved 1classclass

No ChangeNo Change WorsenedWorsened

ControlControl CRTCRT

6%6%

32%32%

59%59%

4%4%

16%16%

52%52%

30%30%

2%2%

P<0.001P<0.001


MIRACLE

Abraham WT NEJM `02

4 weeks

4 weeks

One Year

4 weeks

Acute Testing at Implant

Randomization Prior to Discharge

Pre-OP Evaluation

Best Unichamber Biventricular

No Pace No Pace

Biventricular Best Unichamber

Best Chronic Pacing Mode

FlexStim

PATH CHF:Study Design PATH CHF


Study DesignPre-dischargePre-discharge

Random-Random-izationization

ControlControl

CRT CRT

CRT CRT Double-Double-BlindBlind

BaselineBaseline SuccessfulSuccessfulImplantImplant

——6 Months—6 Months—

≤≤ 1 week1 week

MIRACLECardiac Resynchronization TherapyCardiac Resynchronization Therapy

• Primary Efficacy NYHA Functional Class Quality of life (Minnesota Living with HF) 6-minute Walk Distance

• Secondary Efficacy Included VO2 peak, Exercise Time, LVEF, LVEDD, MR, QRS Duration, Clinical Composite Response

• Other Protocol Specified Endpoints Death or Worsening Heart Failure (Safety) # Days Spent in Hospital (Health Care Utilization)

OMTOMT

Risk of Sudden Death: Risk of Sudden Death: GISSI-2 TrialGISSI-2 Trial

Patients withoutLV Dysfunction

(LVEF >35%)Maggioni AP. Circulation. 1993;87:312-322.

Patients withLV Dysfunction

(LVEF < 35%)No PVBs1-10 PVBs/h> 10 PVBs/h

0.86

A

0.88

0.90

0.92

0.94

0.96

0.98

1.00

0 30 60 90 120 150 180

Days

Su

rviv

al

p log-rank 0.002

0.88

0.90

0.92

0.94

0.96

0.98

1.00

0 30 60 90 120 150 180

Days

Su

rviv

alB

p log-rank 0.0001

0.86


Baseline ex CPX

ImplantAttempt

SuccessfulImplant

ControlICD

CRTCRT + ICD

Pre-dischargeRandomization

6 Month Follow-up

6 Month Follow-up

CRT

DoubleBlinded

StableMedicalTherapy

≤ 1week

• Class NYHA II• Intent to treat analyses• Comparison between groups• Core labs: metabolic exercise,

echocardiography, and neurohormone data

CRT

Long term follow up every 6 months

CPX


MIRACLE ICD II

210 Class II 429 Class III/IV

98 Completed 6M FU 82 Completed 6M FU

2 Death 2

1 Missed 6M FU 1

101 Control (ICD+OPT) 85 CRT (CRT+ICD+OPT)

639 Enrolled and Implant Attempted

19 Unsuccessful 191 (91%) Successful

186 Randomized

5 not randomized- 1 death- 4 LV lead dislodge.


MIRACLE ICD II

Composite Response

36% 34% 31%

58%

22% 20%

0%

20%

40%

60%

Improved No Change Worsened

Pro

port

ion

Control (n=101) CRT (n=85) Chi-square test

P = 0.01


MIRACLE ICD II

Effect on Ventricular Arrhythmias

• 25/101 pts (Control) 89 VT/VF events

• 18/85 pts (CRT) 61 VT/VF events

25%

21%

0%

5%

10%

15%

20%

25%

Control CRT

p = 0.61During 6 Month Randomization Period


MIRACLE ICD II

79

MADIT II Marzo 2002

Precedenti Linee Guida ACC/AHA per ICDs September 2002

COMPANION Maggio 2004

SCD-HeFT Gennaio 2005

La strada alle nuove linee guida

ESC updated Maggio 2005

ACC/AHA updated Agosto2005

CARE-HF Aprile 2005


80

MADIT II Marzo 2002

Precedenti Linee Guida ACC/AHA per ICDs September 2002

COMPANION Maggio 2004

SCD-HeFT Gennaio 2005

ESC updated Maggio 2005

ACC/AHA updated Agosto2005

CARE-HF Aprile 2005


0

1000

2000

3000

4000

1999 2001 2003 2005

Result s Present ed

Cu

mu

lati

ve

Pa

tie

nts

PATH CHF

MUSTIC SR

MUSTIC AFMIRACLE

CONTAK CD

MIRACLE ICD

PATH CHF II

COMPANION

MIRACLE ICD II

CARE HF

La strada alle nuove linee guida

Hospitalization for HF

Mean Mean ±± SEM SEMN N == 16 16

0

10

20

30

40

da

ys

of

ho

sp

ita

liza

tio

n

1 Year1 YearPre-ImplantPre-Implant

1 Year1 YearPost-ImplantPost-Implant

P P == .003 .003

PATH CHF


MUSTIC Inclusion Criteria (67 pts)

• Dilated cardiomyopathy of any etiology• NYHA Class III (not Class IV) • Optimal individual drug therapy • LBBB and QRS duration >150 msec • Not mentioned AVD• LVEF<35% and LVEDD>60mm• 6-MWT<450m• SR & no conventional PM indication


Composite Response

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

por

tion

Pro

por

tion

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

Chi-square test

83

363

↓↓ 77%77%

ControlControln=34n=34

CRTCRTn=18n=18

P<0.001P<0.001

Total HF days Hospitalized


MIRACLE

NYHA Class III/IV HF*, NYHA Class III/IV HF*, EF EF ≤≤ 35%, QRS 35%, QRS ≥≥ 130 ms, 130 ms,Stable HF Medical TherapyStable HF Medical Therapy

No indicationNo indicationfor ICDfor ICD

IndicationIndicationfor ICDfor ICD

MIRACLEMIRACLE(InSync)(InSync)

MIRACLE ICDMIRACLE ICD(InSync ICD)(InSync ICD)

* Separate protocol for MIRACLE ICD Class II* Separate protocol for MIRACLE ICD Class II

Inclusion Criteria

MIRACLE ICD trials

W.T. Abraham for MIRACLE and MIRACLE ICD Investigators


BaselineBaseline ImplantImplantAttemptAttempt

SuccessfulSuccessfulImplantImplant

ControlControl CRT CRT

Pre-dischargePre-dischargeRandomizationRandomization

1, 3, 6 1, 3, 6 Month Month

Follow-upFollow-up

1, 3, 6 1, 3, 6 Month Month

Follow-upFollow-up

CRT CRT

DoubleDoubleBlindedBlinded

StableStableMedicalMedicalTherapyTherapy

≤≤ 11weekweek

CRT CRT

Long term follow up Long term follow up every 6 monthsevery 6 months

• 369 randomized patients369 randomized patients• 182 CONTROL and 187 CRT182 CONTROL and 187 CRT• Control: No pacingControl: No pacing• Treatment (CRT): atrial synched pacingTreatment (CRT): atrial synched pacing• OMT for HF stability maintainedOMT for HF stability maintained• ICD active in all patients of MIRACLE ICDICD active in all patients of MIRACLE ICD

MIRACLE ICD study design



182182 187187

369369

Survival

80%

85%

90%

95%

100%

0 1 2 3 4 5 6

Months Since Randomization

% o

f P

atie

nts

Su

rviv

ing

Control n=402 CRT n=415

P=0.42


Cardiac Resynchronization TherapyCardiac Resynchronization TherapyMIRACLE and MIRACLE ICD Trials

Control 225 214 204 197 191 179 70CRT 228 218 213 209 204 201 99

Patients At RiskPatients At Risk

70%70%

75%75%

80%80%

85%85%

90%90%

95%95%

100%100%

00 11 22 33 44 55 66

Months After RandomizationMonths After Randomization

Eve

nt

Fre

eE

ven

t F

ree

Su

rviv

al

Su

rviv

al (

%)

(%

)

CRTCRT

ControlControlP = 0.033P = 0.033Relative risk = 0.60; Relative risk = 0.60; 95% CI (0.37, 0.96)95% CI (0.37, 0.96)

Time to Death or Worsening HF requiring Hospitalization


MIRACLE

Patients selection• Which is the value of QRS within ?

- 30% pts with wide QRS no Mechanic Asinchronism (Yu, Heart ‘03)

- Which cut-off considerate for pts selection ? - Relationship between QRS duration and LV dilation ?

Ventricoli meno dilatati ma con dissincronie regionali

non alterano l’ECG di superficie (durata QRS normale)? (Auricchio A, Yu CM – Heart ‘04)


• Età avanzata• Genesi ischemica della miocardiopatia (controverso)• Assenza di insufficienza valvolare mitralica (Reuter S et a. Am J Cardiol 2002) o IM severa

(Achilli A, Italian Heart J ‘04)• Maggiori volumi telediastolici e telesistolici (Bax JJ, JACC ‘04)• FA permanente - controverso: ablazione NAV?

Speranza di recupero RS con riduz. IM e reverse LV remodeling?

• Classe NYHA IV (?)

Why are the Non-Responders ?Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

E E AA E E AA

Mitral flowMitral flowICTICT IRTIRTETET

Aortic flowAortic flow

ICT+IRT = MPIICT+IRT = MPIETET


LMPI LMPI

RMPI RMPI

1.2 ± 0.671.2 ± 0.67

1.35 ± 0.761.35 ± 0.76

0.8 ± 0.50.8 ± 0.5

0.81 ± 0.390.81 ± 0.39

0.0090.009

0.040.04

Baseline Follow-up p<




Influence of Pacing-site

Sinusnode

AVnode

Bundlebranch or

diffuse block

Delayed conduction

• Delayed AV sequence

• Mitral regurgitation

• Decreased filling time

Delayed Ventricular ActivationDelayed Ventricular Activation

What is abnormal in the HF pts?What is abnormal in the HF pts?Cardiac Resynchronization TherapyCardiac Resynchronization Therapy


Spragg DD, Circulation ‘03

Regional Alterations in Protein Expression in the Dyssynchronous Failing Heart


VO2

(ml/

min

/mVO

2 (m

l/m

in/m

22 ))


OO22ERER


DISOXIADISOXIA


DODO22 = = QQC C X CaX CaOO22

VOVO22 = = DODO2 2 X X OO22ERER

NormalNormal

DODO22 = =QQC C x (1,34 xx (1,34 x Hb x Sa Hb x SaOO22) x 10) x 10


Physiologic pacing in ICDPhysiologic pacing in ICD

Spragg DD, Circulation ’03

Regional Alterations of Protein Expression

11 CHF-dyssynchronous Interstitial remodelling: fibrosis α-TNF, apoptosis


http://circres.ahajournals.org/content/vol96/issue5/images/large/1FF1.jpeg



Influence of Pacing-site

Blanc et al., Circulation 1997 23 pts mean ± SD

90

100

110

120

130

140

150

SYSTOLIC SYSTOLIC Blood PressureBlood Pressure

RVARVA LV BVRVORVOBASBAS

mm

Hg

mm

Hg

p<.01 p<.03

0

10

20

30

40

Pulmonary Capillary Pulmonary Capillary Wedge PressureWedge Pressure

RVARVA LV BVBVRVORVOBASBAS

p<.01 p<.01

Acute studiesCardiac Resynchronization TherapyCardiac Resynchronization Therapy

Kass, Circulation 99

% C

hang

e%

Cha

nge

RVSRVS LVSLVS

SYSTOLIC PressureSYSTOLIC Pressure

0

2

4

6

8

10

RVSRVS LVSLVS

Max LV Dp/DtMax LV Dp/Dt

0

10

20

30

40

meanmean±±SDSDLBBBRBBB

p<.05p<.05

p<.01p<.01

p<.01p<.01nsns

Acute studiesCardiac Resynchronization TherapyCardiac Resynchronization Therapy

Effects of Ventricular Dyssynchrony on Cardiac Function

Reduced diastolic filling time 1 Weakened contractility 2 Impaired Systolic function (depressed Dp/Dt) Protracted MR 2 Mechanical and temporal dyssynchrony Abnormal septal wall motion Post systolic regional contraction 3

1. Grines CL, et al Circulation 1989 2. Xiao HB, et al Br Heart J 1991 3. Søgaard P, et al. J Am Coll Cardiol 2002

Diminished SV


LVRV

• WHO? Which criteria ?

• WHEN? Which NYHA class ?

• WHERE? RV+LV / LV ?

• WHY? Symptoms / Mortality ?

CRT:CRT: KEY QUESTIONS KEY QUESTIONS


Cardiac Resynchronization TherapyCardiac Resynchronization TherapyWhy the need of CRT ?

Debole Contrazione

AttivazioneSistemi

Neuro-ormonali

Ritenzione idrico-salina

CHF

Attivazione Asincrona

Who are the Non-Responders ?

• STRUMENTALE parametri Eco-TDI-SR, ECO3D (no reverse remodelling)

• CLINICI Sopravvivenza, NYHA class, CHF-H, 6MWT, VO2 etc

• BIPHASIC CURVE


Who are the Non-Responders ?• Improve LVEF less then 25%

(Penicka M, Circulation ’04)• Reduction < 10% LVESV

(Yu CM, Circulation ‘05)• Reduction LVESV index <15%

(Pitzalis MV, JACC ‘02)• Class NYHA invariate or

improvement less then 25% of 6-MWT (Bax et a. JACC 2004)

• Invariate NYHA class or 6MWT, death, CHF-H, No change or improvement < 10% of VO2 peak (Lecoq G, EHJ ’05, MUSTIC, PATH-CHF, COMPANION)

• BNP plasma level, MR entity, HRV, persistence of Inter and Intra-Ventricular Conduction Delay.


Optimization of Pacing VV delayOttimizzare l’intervallo VV comporta un ulteriore incremento della FE anche nei responders (Sogaard, Circulation ‘02)

Il 50% dei paz. mostra beneficio nella preattivazione VS (20-60 msec), il 50% nella preattivazione VD (in acuto) (Porciani, Am J Card ‘05)


(Bordachar P, JACC ‘04)

• Inaccurata selezione dei pazienti sulla base degli indici predittivi

• Presenza di comorbidità elevata

• Stimolazione biventricolare tecnicamente inefficace

• Severe CHF or hemodinamic instability

Why are the Non-Responders ?Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

What does it mean wide QRS ? What does it mean wide QRS ? LBBB more prevalent with Impaired LV

Systolic Function

38%

24%

8%

Moderate/SevereHF (2)

Impaired LVSF(1)

Preserved LVSF(1)

1 Year Survival

11%

16%

QRS <120ms

QRS > 120 ms

P < 0.001

1. Masoudi, et al. JACC ‘032. Aaronson, et al. Circ 97


Long-term (45 Mo) Survival

34%

49%

QRS < 120 ms

QRS > 120 ms

Iuliano et al. AHJ 2002N=669

P < 0.001

Baldasseroni S. EHJ `02 N=5,517

What does it means DYSSYNCHRONYSM ?• VEST study analysis• NYHA Class II – IV pz• 3,654 ECGs digitally

scanned• Age, creatinine, LVEF,

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

• Relative risk of widest QRS group 5x greater than narrowest

60%

70%

80%

90%

100%

0 60 120 180 240 300 360Days in Trial

Cu

mu

lati

ve S

urv

ival

QRS Duration (msec)

<9090-120

120-170170-220

>220

Adapted from Gottipaty et al. JACC 1999; 33(2):145A (abstract 847-4)


%

Mortality rate in patients with or without LBBB (5517 pts)

0

5

10

15

20

25

301 Year-Mortality

Total Sudden Death

LBBBNo LBBB

Study population

11.9

16.1

10.5

5.5 4.97.3

p<0.001

p<0.001

No LBBBUnadjusted 1

Adjusted 1

RR of Total Death

No LBBB

Unadjusted 1

RR of Sudden Death

Adjusted 1

1.70(1.34-2.21)

1.36(1.15-1.61)

LBBB

1.58(1.21-2.06)

LBBB

1.34(1.05-1.42)

INCHF


LBBB: 25,2%

1 Framingham Heart Study (1948 – 1988) in Atlas of Heart Diseases.2 American Heart Association. Heart Disease and Stroke Statistics—2003 Update.

CHF Patients Survival ResultsCHF Patients Survival Results11

1009080

70

605040

3020100

Prob

abili

ty o

f su

rviv

al, %

Men (Men (n n = 237)= 237)Women (Women (nn = 230) = 230)

Time after CHF diagnosis, years0 2 4 6 8 10


years.2


years.2


Synchronizing the Ventricles: Separation of E- and A- Waves

Surface ECG

IVRT IVRT

A-waveA-wave

Aortic Flow

E-waveE-waveSpectral Doppler

PR PR

LVFTLVFT

Aortic Flow


Karloff, PACE ‘87

Cumulative Enrollment in C.R. Cumulative Enrollment in C.R. Randomized TrialsRandomized Trials

0

1000

2000

3000

4000

1999 2001 2003 2005Result s Present ed

Cum

ulat

ive

Patie

nts

PATH CHF

MUSTIC SR

MUSTIC AFMIRACLE

CONTAK CD

MIRACLE ICD

PATH CHF II

COMPANION

MIRACLE ICD II

CARE HF

• • Actual � ProjectedActual � ProjectedDOUG SMITHDOUG SMITH



Kerchhoffs RC, J CV Electr 03

Influence of Pacing-site in CANINE model



Cardiac Resynchronization TherapyCardiac Resynchronization TherapyInfluence of Pacing-site in CANINE model

Kerchhoffs RC, J CV Electr 03


http://circ.ahajournals.org/cgi/content/full/113/7/953/FIG5

Ansalone G, GIEC ‘05

Pts with LBBB, after CRT PW-DTI, shows an improvement of

mitralic CO respect E-A interval, with reduction of systolic

velocity peak

Patients selectionCardiac Resynchronization TherapyCardiac Resynchronization Therapy

INTRA-VCD Eco M-mode (validate in QRS wide) PW-TDI Strain Rate Echo 3D

Optimization of Pacing VV delayOttimizzare l’intervallo VV comporta un ulteriore incremento della FE anche nei responders (Sogaard, Circulation ‘02)

Il 50% dei paz. mostra beneficio nella preattivazione VS (20-60 msec), il 50% nella preattivazione VD (in acuto) (Porciani, Am J Card ‘05)


(Bordachar P, JACC ‘04)

laterale (35%) anteriore (26%) posteriore (23%) infero-settale (16%)

(Ansalone, Am Heart J ‘01)

Inferiore (45%)Laterale (30%)Posteriore (25%)Settale (16%)Anterosettale (5%)

(Yu, JACC ‘05)

Optimization of CRTCardiac Resynchronization TherapyCardiac Resynchronization Therapy

I segmenti maggiormente interessati dal ritardo sono:

If the objective of CRT is pacing the more delayed wall, the selection of the site of stimulation will be relevant

Improvement in Peak VOImprovement in Peak VO22

-0.5-0.5

0.00.0

0.50.5

1.01.0

1.51.52.02.0



ml/

kg/m

inm

l/kg

/min

P=0.009P=0.009

Improvement in Improvement in Total Exercise TimeTotal Exercise Time

00

3030

6060

9090

120120



seco

nds

seco

nds

P=0.001P=0.001

Baseline Baseline (ml/kg/min)(ml/kg/min)

13.7 ± 3.8

14.0 ± 3.5

BaselineBaseline (secondsseconds)

462 ± 217

484 ± 209

Metabolic ExerciseMIRACLE

Nelson et al. Circulation ‘00Ukkonen et al. Circulation ‘03


Current treatment of CHFFunctional improvement

Mortality reduction

– pump failure

– sudden death

DrugsDrugsLV/LV/BiVBiV Pacing Pacing ?

ICDICDDrugsDrugs

LV/LV/BiVBiVICD ?ICD ?

≈ 15% of all conventional ICD could be eligible for BVP


2006 orvieto, giornate cardoilogiche orvietane. il trattamento non farmacologico dello scompenso...

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