Simposio NUOVE TECNOLOGIE IN CARDIOLOGIA … · Diuretici (%) 87 89 88 0.415 Nitrati (%) 17 23 46...

Terapia di resincronizzazione nello scompenso cardiacoStefano FumagalliUnità di Cura Intensiva - SOD Cardiologia e Medicina GeriatricaAOU Careggi e Università di Firenze

Simposio

NUOVE TECNOLOGIE IN CARDIOLOGIA GERIATRICA

Giovedì 2 Dicembre 2010

Patie

nts

Free

of D

eath

fr

om A

ny C

ause

(%)

Days

Cardiac resynchronization (N=409, Age: 67 years)

Medical Therapy(N=404, Age: 66 years)

29.4 months

20%

30%

HR=0.64 - 95%CI=0.48-0.85 p<0.002

LVEF: 25%; NYHA III / IV

Cleland JGF et al., 2005

Patient Population ClassCRT-P / CRT-D is recommended to reduce MORBIDITY & MORTALITY

NYHA function Class III / IVLVEF <35%, QRS >120 ms, SROptimal Medical Therapy(Class IV pts ambulatory)

I A

CRT, preferentially by CRT-D, is recommended to reduce MORBIDITY or to prevent disease PROGRESSION

NYHA function Class IILVEF <35%, QRS >150 ms, SROptimal Medical Therapy

I A

CRT-P / CRT-D SHOULD be considered to reduce MORBIDITY

NYHA function Class III / IVLVEF <35%, QRS >130 ms, AFPacemaker dependency induced by AV nodal ablation

IIa B

Slow ventricular rate and frequent pacing IIa C

Dickstein K et al., 2010

Prob

abili

ty o

f Eve

nt-fr

ee

Surv

ival

Death or Hospitalization for HF Death

Mean Follow-up: 40±20 months

Prob

abili

ty o

f Sur

viva

l

Years of Follow-up Years of Follow-up

HR=0.75 – 95%CI=0.64-0.87; p<0.001 HR=0.75 – 95%CI=0.62-0.91; p=0.003

ICD-CRTN=297 (33.2%)

ICDN=364 (40.3%)

ICD-CRTN=186 (20.8%)

ICDN=236 (26.1%)

ICD-CRT (N=894)Age: 66 yrs; Males: 84.8%; LVEF: 22.6%; NYHA II: 79.2%

ICD (N=904)Age: 66 yrs; Males: 81.0%; LVEF: 22.6%; NYHA II: 80.8%

Tang ASL for the RAFT Investigators, 2010

19-79(N=22193)

Adm

issi

ons

(N)

80-85(N=3702)

>85(N=992)

Age-groups

CRT-D

ICD

CRT-P

PREMIER’s Perspective Comparative Database (2004-2005)N=26887 - Mean Age=70 yearsAge >80 years – N=4694 (17.5%)

Swindle JP, Arch Intern Med, 2010

0

Leng

th o

f Sta

y (M

edia

n, d

ays)

1-2 >3Charlson Comorbidity Index

19-79 years

80-85 years

>85 years

Swindle JP, Arch Intern Med, 2010

P=0.09

P<0.001

P<0.001

Length of Stay in Hospital by Age and Comorbidity in CRT-D Patients

19-79(N=14456)

Com

plic

atio

ns -

Freq

uenc

y (%

)

Age-groupsSwindle JP, Arch Intern Med, 2010

80-85(N=2583)

>85(N=765)

P=0.03

19-79(N=14456)

Mor

talit

y (%

)

Age-groups

80-85(N=2583)

>85(N=765)

P<0.001

0

Perc

enta

ge m

orta

lity

(%)

Follow-up (days)

180 360 540 7200

5

10

15

20

25

70 159 123 87 67Patients at risk

>70 yearsN=68

<70 yearsN=102

17%

10%

1 year

P=NS

Age: 66±11 yrsN=170

Bleeker GB, 2005

Caratteristiche cliniche della popolazione del Registro Italiano InSync / InSync ICD, per gruppi di età

Gruppi di età (anni) <65

(N=571) 65-74

(N=740) >75

(N=476) P

Età (anni) 57 ± 7 70 ± 3 78 ± 3 / Uomini (%) 84 81 76 0.003 BPCO (%) 5 7 6 0.088 Diabete (%) 8 9 6 0.312 IRC (%) 3 8 4 0.001 >2 patologie (%) 2 4 3 0.099 CAD (%) 39 50 50 <0.001 LVEDD (mm) 70 ± 10 69 ± 9 68 ± 9 0.015 LVESD (mm) 60 ± 12 58 ± 10 57 ± 11 0.016 FE (%) 26 ± 8 26 ± 7 27 ± 8 0.123 Durata QRS (ms) 167 ± 33 165 ± 31 162 ± 32 0.136 Ricoveri (n) 1.6 ± 1.4 1.6 ± 1.5 1.7 ± 1.4 0.256 FA permanente (%) 11 18 21 <0.001 Diuretici (%) 87 89 88 0.415 Nitrati (%) 17 23 46 0.001 AA Classe III (%) 34 38 34 0.312

IRC: insufficienza renale cronica; CAD: cardiopatia ischemica; Ricoveri: ricoveri per CHF nei 12 mesi precedenti; AA: antiaritmici Fumagalli S. EHJ, 2009

45

37

60

0

15

30

45

60

75P <0.001

<65 65–74 >75

Gruppi di età (anni)

Terapia con β-bloccanti e ACE-inibitori o sartani, per gruppo di età. I risultati del Registro Italiano InSync / InSync ICD

79

71 70

0

20

40

60

80

Gruppi di età (anni)

P=0.001

Uso

di A

CE-

I e a

nti-A

TII (

%)

<65 65–74 >75

Uso

di β

‐blo

ccan

ti (%

)

Fumagalli S. EHJ, 2009

Variazioni dei diametri e della frazione di eiezione del ventricolo sinistro (VS) con CRT durante il follow-up, per gruppo di età. I risultati del Registro Italiano InSync / InSync ICD

Base 6 mesi 12 mesiFollow-up

Dia

met

ri VS

(mm

)

Telediastolico

Telesistolico

**

****

****

**

****

**

******

**: p<0.001 vs. Base

6666

64

6970

68

5354

51

5860

57


Base 6 mesi 12 mesi

Follow-up

(%)

FE VS

****

**

******

2627

26

3437

34

<65 65 – 74 >75Gruppi di età (anni)

Cla

sse

NYH

A

2.9

1.9 2

3

2 2.1

3

22.2

0

1

2

3

4

P = NS

<65 65–74 >75

Base

Classe NYHA in condizioni di base e durante il follow-up, per gruppo di età. I risultati del Registro Italiano InSync / InSync ICD

<65 65–74 >75

6 mesi<65 65–74 >75

12 mesi

** * ** *

<65 anni – p per trend <0.00165 – 74 anni – p per trend <0.001>75 anni – p per trend <0.001

*: p<0.001 vs. Base


Res

pond

eral

la C

RT

(%)

58 60 62

0

20

40

60

80

100

P = NS

<65 65–74 >75Gruppi di età

Responder alla CRT ed utilizzo della CRT-D, per gruppo di età. I risultati del Registro Italiano InSync / InSync ICD

<65 65–74 >75

4843

29

0

20

40

60

80

Gruppi di età

P <0.001

Util

izzo

CR

T-D

(%)

CRT-D - CRT + ICDResponder alla CRT: volume telesistolico VS >10% a 6 mesi


Res

pond

eral

la C

RT

(%)

58 60 62

0

20

40

60

80

100

P = NS

<65 65–74 >75Gruppi di età

Responder alla CRT ed utilizzo della CRT-D, per gruppo di età. I risultati del Registro Italiano InSync / InSync ICD

<65 65–74 >75

4843

29

0

20

40

60

80

Gruppi di età

P <0.001

Util

izzo

CR

T-D

(%)

CRT-D - CRT + ICDResponder alla CRT: volume telesistolico VS >10% a 6 mesi


CRT-D – HR=0.9495%CI=0.70-1.25;

p=0.664

Responder alla CRTNon Responder alla CRT

<65 anni

0.00.20.40.60.81.0

0 500 1000 1500 2000Follow-up (giorni)

Sopr

avvi

venz

a

p=0.003

65-74 anni

0 500 1000 1500 2000Follow-up (giorni)

P<0.001

>75 years

0.00.20.40.60.81.0

0 500 1000 1500 2000Follow-up (giorni)

Sopr

avvi

venz

a

P<0.001Responder alla CRT: riduzione del volume telesistolico del VS >10% nella valutazione a 6 mesi

Sopravvivenza durante il follow-up, per risposta alla CRT & gruppo di età. I risultati del Registro Italiano InSync / InSync ICD


Σ -10.5%

Σ -13.6%

Σ -11.6%

HR (95% CI) p Value

Età <65 anni 1 /65-74 anni 1.17 (0.80-1.69) NS>75 anni 1.57 (1.06-2.35) 0.026

Uomini 1.38 (0.90-2.12) NS

Insufficienza renale 1.29 (0.75-2.22) NS

Cardiopatia ischemica 1.18 (0.87-1.60) NS

FE VS, per ∆ % 0.96 (0.94-0.98) <0.001

FA permanente 1.63 (1.16-2.30) 0.005

ACE-I / ARB 0.72 (0.52-0.98) 0.038

β-bloccanti 0.49 (0.35-0.67) <0.001Responder CRT 0.37 (0.27-0.51) <0.001

Variabili cliniche correlate alla prognosi durante CRT nel Registro Italiano InSync / InSync ICD. Risultati del modello di Cox


ICD Better

HR=0.72 (0.58-0-89), p=0.003

HR=0.65 (0.50-0-83), p<0.001

IRIS, 2009DINAMIT, 2004

ICD Trials that Enrolled Early After Acute MI

OVERALLSCD-HeFT, 2005MADIT-II, 2002DEFINITE, 2004

ICD Trials Relevant to the Current Practice

OVERALL

Medical Therapy BetterHR (95% CI)

Younger patients – N=3232

Santangeli P, Di Biase L, 2010

ICD Better

HR=0.72 (0.58-0-89), p=0.003

HR=0.65 (0.50-0-83), p<0.001

IRIS, 2009DINAMIT, 2004


OVERALLSCD-HeFT, 2005MADIT-II, 2002DEFINITE, 2004


OVERALL

Medical Therapy BetterHR (95% CI)

Younger patients – N=3232

Santangeli P, Di Biase L, 20100.5

IRIS, 2009 *DINAMIT, 2004 * *


OVERALLSCD-HeFT, 2005 *MADIT-II, 2002 * *DEFINITE, 2004*


OVERALL HR=0.97 (0.78-1.19), p=0.075

HR=0.81 (0.62-1.05), p=0.11

1 2

Elderly patients – N=2551

*/** = >65 / >60 yrs oldSantangeli P, Di Biase L, 2010

Age-groupsEpstein AE, Heart Rhythm, 2009

2-ye

ar M

orta

lity

(%)

18-39 40-49 50-59 60-69 70-79 >80

P=0.05vs 18-39 yrs

The Advancement in ICD Therapy (ACT) Registry – N=4566

Sudden Cardiac Death

Non Sudden Cardiac Death

Non Cardiac Death

P=0.05vs 18-39 yrs

B

1-ye

ar L

engt

h of

Sta

y fo

r CH

F (d

ays)

Delnoy PPHM, Am Heart J, 2008

6-M

in W

alki

ng T

est D

ista

nce

(m)

Study period

1-yr FU

B

<75 (N=159)

B 3-Mo 1-Yr 2-Yr

Age <75 years

P=0.003

1-yr FU

>75 (N=107)

P<0.001

Age >75 years

* **

**

*: p<0.01 vs. Baseline**: p<0.01 vs. >75 years

Hoth KF, Clin Interv Aging, 2008

B 3m

SF-3

6 (s

core

)

Physical Function

0

10

20

30

40

50

60

70

Age: 68±8 yrs (range: 56-84)– N=21EF: B=30% - 3m=39%, p<0.016-mWT : B=351 m - 3m=381 m, p<0.05

B 3m B 3m B 3m B 3m B 3m B 3m B 3m

Role-Physical Function

Pain Index

General Health

Perception

Vitality Score

Social Function

Role-Emotional Function

Mental Health Index

80

90

B: baseline3m: 3 months

F n

Vitality Score

P<0.01

Hoth KF, Clin Interv Aging, 2008

B 3m

SF-3

6 (s

core

)

Physical Function

0

10

20

30

40

50

60

70

Age: 68±8 yrs (range: 56-84)– N=21EF: B=30% - 3m=39%, p<0.016-mWT : B=351 m - 3m=381 m, p<0.05

B 3m B 3m B 3m B 3m B 3m B 3m B 3m

Role-Physical Function

Pain Index

General Health

Perception

Vitality Score

Social Function

Role-Emotional Function

Mental Health Index

80

90

B: baseline3m: 3 months

P<0.01 F n

Vitality Score

P<0.01

79.3

79.4

79.5

79.6

79.7

79.8

79.9

80.0

80.1

<2.54 2.54-2.92 >2.92

Adju

sted

mea

n To

tal B

rain

Vol

ume

(%)

N=501 N=502 N=501

-0.36 -p=0.04

-0.35 -p=0.04

Cardiac Index (L·min·m2) Tertiles

Age: 61±9 yrs - Female: 54%

Jefferson AL, Circulation, 2010

Brain MRI (% of cranial volume)Total brain volume: 79.66%White matter hyperintensity: 0.09%

Baseline Follow-up6-months

40

50

60

10

20

30

40

Mea

n ve

loci

ty (c

m/s

)

Responders*

Patients - Age: 68 yrs; LVEF: 29%; QRS: 152 msControls - Age: 66 yrs; LVEF: 32%; QRS: 110 ms

Van Bommel RJ, 2010

Cerebral blood flow -Transcranial Doppler ofthe right middle cerebral artery

Controls

Non-responders

Cerebral blood flow

*/°: p<0.01 / p<0.05 vs Controls & Non-responders

Baseline Follow-up6-months

MLHFQ

Non-responders

Responders°

(sco

re)

Responders – 6-month reduction >15% of LV end-systolic volume

MLHF – Minnesota Living with Heart Failure Questionnaire

P=0.005vs Baseline

P<0.001vs Baseline

(N=16)

(N=14)

(N=16)

Dixit NK, Clin Cardiol, 2010

5662

B 3-monthAge

& E

duca

tion

Conv

erte

d T-

scor

es

AttentionDigit Span

0

10

20

30

40

50

60

70 P=0.015

47

55

B 3-month

Speed ofProcessingDigit Symbol

P<0.001

47 49

B 3-month

ExecutiveFunctionTMT Part B

P=NS

4751

B 3-month

LanguageCOWA

P=0.004

Age: 55±12 – N=20Baseline (B) EF: 17%3-month EF: 30%

79827666753872437139

73299

55578

4790942701

36777

2249019450

180171642715805

0

20000

40000

60000

80000

55

∆Q

ualit

y ad

just

ed li

fe y

ears

(QAL

Ys)

Starting Age (years)

3.16

3.624.08

4.394.72

4.38

5.25

6.06

6.867.42

4.73

5.78

6.75

7.72

8.54

0

1

2

3

4

5

6

7

8

9

Incr

emen

tal C

ost p

er Q

ALY

(€)

60 65 70 75

CRT + ICD (CRT-D)CRTMedical Therapy (MT)

55

Starting Age (years)60 65 70 75

CRT-D vs. CRTCRT-D vs. MTCRT vs. MT

Estimates from individual patient data from the CARE-HF & the COMPANION trials

Yao G, Eur Heart J, 2007

Conclusioni

La CRT determina il miglioramento della geometria e della funzione del VS in pazienti di tutte le etàI benefici della CRT sono apprezzabili anche in termini di capacità funzionale e qualità della vitaL’aumento della perfusione cerebrale, indotto dalla CRT, potrebbe rallentare il deterioramento cognitivo dei pazienti di età avanzata con scompenso cardiacoL’ undertreatment farmacologico costituisce un problema reale, soprattutto nei più anziani L’uso della CRT in età avanzata è vantaggioso anche in termini economiciSono necessari studi clinici per confermare questi risultati ottenuti da registri di ampie proporzioni

1997

Car

diac

Dev

ice

Impl

anta

tion

US

Nat

iona

l Est

imat

es(N

)

Years

CRT-D

CRT-P

AICD

Zhan C, J Gen Intern Med, 2008

1998 1999 2000 2001 2002 2003 2004

Primary source of data: The Healthcare Cost and Utilization Project Nationwide Inpatient Samples(by the Agency for Healthcare Research and Quality)

0

10

20

30

40

1-year 2-year

Mor

talit

y (%

)

22.4

3-year

Left-BB/CAD

Left-BB/non-CAD

Right-BB/CAD

Right-BB/non-CAD41.9

HR=1.99 95%CI=1.75-2.26

Medicare ICD Registry (2005-6)Mean Follow-up: 40 monthsAge: 73 years - N=14946

Bilchick KC, Circulation, 2010

50-59 60-69 70-79 >80Age (years)

0.97

1.23

1.75

0.5

1

1.5

2

2.5

3-ye

ar M

orta

lity

(HR)

Diabetes

Left atrium >47 mm

Renal dysfunction

NYHA IVMR jet area >10 cm2

LVDD >74 mm

QRS <120 ms

Age >65 years

OR0 1 5 10 15 20

0.473

0.391

0.128

0.038

0.020

0.004

0.749

0.758

OR=13.80

OR=4.83

OR=4.62

Antonio N, J Interv Card Electrophysiol, 2010

LVDD: left ventricular end-diastolic diameter

MR: mitral regurgitation

Age: 62±11; Age >65 yrs: 36 (41%)Men: 55 (63%)LVEF: 24% - (N=87)Predictors of non-response to cardiac

resynchronization therapy

Diabetes

Left atrium >47 mm

Renal dysfunction

NYHA IVMR jet area >10 cm2

LVDD >74 mm

QRS <120 ms

Age >65 years

OR0 1 5 10 15 20

0.473

0.391

0.128

0.038

0.020

0.004

0.749

0.758

OR=13.80

OR=4.83

OR=4.62

Antonio N, J Interv Card Electrophysiol, 2010

LVDD: left ventricular end-diastolic diameter

MR: mitral regurgitation

Age: 62±11; Age >65 yrs: 36 (41%)Men: 55 (63%)LVEF: 24% - (N=87)Predictors of non-response to cardiac

resynchronization therapyOR=0.79

0.5

0.6

0.7

0.8

0.9

0 2

Even

t Fre

e Pr

obab

ility

4 6 8 10

1.0

12Months post Implant

Q1-0-92% N=467

Q4-100% N=362P<.001 vs Q1

Q3-98-99% N=509P=.0004 vs Q1

Q2-93-97% N=474P=.0013 vs Q1

N=1812 - Age: 72±11Men: 72%Follow-up: 10.7% months

Death & HF hospitalization by percentage of biventricular pacing (quartiles)Q2-Q4 vs Q1 – HR=0.56, p<0.00001

Koplan BA, J Am Coll Cardiol, 2009

18-39(120)

ICD

–C

RT-

D Im

plan

tatio

ns (%

)

Age-groups

Epstein AE, Heart Rhythm, 2009

November 2004 – March 2006

2-ye

ar M

orta

lity

(%)

Age-groups

40-49(394)

50-59(918)

60-69(1260)

70-79(1326)

>80(548)(N)

18-39 40-49 50-59 60-69 70-79 >80

P=0.05 P=0.03

The Advancement in ICD Therapy (ACT) Registry – N=4566

Simposio NUOVE TECNOLOGIE IN CARDIOLOGIA … · Diuretici (%) 87 89 88 0.415 Nitrati (%) 17 23 46...

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Transcript of Simposio NUOVE TECNOLOGIE IN CARDIOLOGIA … · Diuretici (%) 87 89 88 0.415 Nitrati (%) 17 23 46...