SCC: ‘device’ utili anche nell’anziano? Stefano Fumagalli

Aritmologia Geriatrica, SOD Cardiologia e Medicina Geriatrica,

AOU Careggi e Università di Firenze

SCC: ‘device’ utili anche nell’anziano?

La terapia di resincronizzazione

cardiaca (CRT)

Despite the compelling findings from several CRT trials, it must be recognized that patients enrolled in these

studies were highly selected

Specifically, few patients >75 were enrolled …

Thus, RCT evidence for efficacy of CRT in patients

>75 years is lacking and, as previously noted, extrapolation of data from trials in much younger

patients to the very elderly may not be justified due to

age-related alterations in both the risks (higher) and benefits (potentially lower) in older patients

2011

0.0

0.2

0.4

0.6

0.8

1.0

0 500 1000 1500 2000

Follow-up (days)

Su

rviv

al

75 years – p=0.080

75 years – p=0.005

Survival in the InSync Registry by age-group

Results of the Kaplan-Meier analysis

Mean length of follow-up:

19±13 months

Fumagalli S,

2011

Responder alla CRT

Non Responder alla CRT

NYHA III-IV

Atrial fibrillation

Ischaemic aetiology

CRT-P vs. CRT-D

Age groups

QRS durations

Women

0.50 1.00 1.50 2.00 2.50 3.00 3.50

Odds Ratio

1.91 *

1.81 *

1.75 *

1.65 *

1.05

0.96

0.63

Mortality

N=2111 (median age: 70 years)

>75 years: 30.6%

*: p

Follow-up (days)

Su

rviv

al p

rob

ab

ilit

y

0 1000 2000 3000 4000

0.0

0.2

0.4

0.6

0.8

1.0

Beta-blockers - YES

Beta-blockers - No

Influence of beta-blocker therapy on survival

Multivariate analysis

HR (95%CI) = 2.3 (1.6-3.8)

P=0.003

CRT-D; N=239; EF: 26%; FU: 43 months;

died: 25% - age: 69; survived: 75% - age: 66

Kreuz J et al, 2012

81.1 80.277.2

0

20

40

60

80

100

6 Min Walk Test

(Change, m)

Peak VO2

(Change,

mL/min)

MIRACLE N=453, III-IV

MUSTIC SR N=58, III

MIRACLE ICD N=369, III-IV

CONTAK CD N=227, II-IV

60

40

20

0

-20

3

2

1

0

(N, NYHA Class)

Improvements in exercise capacity in patients with moderate-to-severe

heart failure by CRT. A review of the results of clinical trials

Linde C et al,

2012

CRT Control

P

Bogale N et al., 2012

% o

f P

ati

en

ts

Much

better

A little

better

No

change

A little

worse

Much

worse

Dead

Patient self-reported global assessment and

rate of death during follow-up

81%

Class I – CRT IS indicated for patients …

1. … who have LVEF 150 ms), and NYHA

class II, III, or ambulatory IV symptoms on GDMT

Class IIa – CRT CAN be useful for patients …

1. … who have LVEF

Class III – CRT IS NOT recommended for patients

…

1. … with NYHA class I or II symptoms and non-

LBBB pattern (QRS duration

SCC: ‘device’ utili anche nell’anziano?

Il defibrillatore impiantabile (ICD)

Annual Mortality

Su

dd

en

Death

as %

of

To

tal M

ort

ali

ty

Sudden death as a percentage of total mortality by gender and Seattle Heart

Failure Model (SHFM) scores (N=8337, women: 20%, age: 63+11 years, NYHA II Class: 51%, LVEF: 25+6%)

PRAISE, UWMD HF Cohort, Val-Heft,

COMET, IN-CHF

Important Differences in Mode of Death Between Men and Women

with Heart Failure Who Would Qualify For a Primary Prevention ICD

Rho RW, 2012

Follow-up: 2.4 years

Annual Mortality

Pu

mp

Fail

ure

Death

as %

of To

tal

Mo

rtali

ty

Pump Failure death as a percentage of total mortality by gender and Seattle

Heart Failure Model (SHFM) scores (N=8337, women: 20%, age: 63+11 years, NYHA II Class: 51%, LVEF: 25+6%)

PRAISE, UWMD HF Cohort, Val-Heft,

COMET, IN-CHF

Important Differences in Mode of Death Between Men and Women

with Heart Failure Who Would Qualify For a Primary Prevention ICD

Rho RW, 2012

Follow-up: 2.4 years

N=7

27-63%

N=12

13-50%

N=6

15-49%

N=30

8-75%

N=7

10-36%

N=10

8-38%

N=6

10-33%

N=30

5-75%

Time post-implant (months) Time post-implant (months)

Pre

vale

nce (

%)

Symptoms of Anxiety Symptoms of Depression

45 Studies assessing >5000 patients through 2009 Magyar-Russell G, 2011

N = number

of studies

N = number

of studies

ATP ICD shocks

STAI-ST NS NS

STAI-TR NS NS

BAI NS NS

BDI NS NS

FQ NS NS

P & A NS NS

AD NS NS

ATP ICD shocks

NS NS

NS 0.01

NS 0.001

NS 0.03

NS 0.01

NS NS

NS 0.01

Psychometric variables assessed before ICD-

implantation as predictors of later frequency

of ATPs and ICD-shocks and …

… frequency of ATPs and ICD-

shocks as predictors of

psychometric variables at 12

months

ATP: anti-tachycardia-pacing (N); ICD shock: ICD shocks (N); STAI-ST / STAI-TR: Spielberger State Trait

Anxiety Inventory – State anxiety / Anxiety as a trait; BAI: Beck Anxiety Inventory; BDI: Beck’s Depression Inventory; FQ: Fear Questionnaire; P & A: Panic and Agoraphobia Scale; AD: Anxiety Disorder

N = 54; Age: 57+14 years; MMSE score: 29.4 Schulz SM, 2012

Arm A

Conventional

Arm B

High-Rate

Arm C

Duration-Delay

Zone 1:

>170 bpm, 2.5 s delay

Onset/stability detection

ATP + Shock

Zone 1:

170 bpm

Monitor only

Zone 1:

>170 bpm, 60 s delay

Rhythm ID Detection

ATP + Shock

Zone 2:

>200 bpm, 1 s delay

Quick convert ATP

Shock

Zone 2:

>200 bpm, 2.5 s delay

Quick convert ATP

Shock

Zone 2:

>200 bpm, 12 s delay

Rhythm ID Detection

ATP + Shock

Zone 3:

>250 bpm, 2.5 s delay

Quick convert ATP

Shock

Summary of ICD programming in the three treatment arms

in the Multicenter Automatic Defibrillator Implantation Trial – Reduce

Inappropriate Therapy (MADIT-RIT)

ATP: anti-tachycardia pacing Moss AJ, 2012

Cumulative Probability of First Occurrence of Inappropriate Therapy by

Treatment Group in the Multicenter Automatic Defibrillator Implantation

Trial – Reduce Inappropriate Therapy (MADIT-RIT)

Years of Follow-up

Cu

mu

lati

ve P

rob

ab

ilit

y o

f

Fir

st

Occu

rren

ce o

f

Inap

pro

pri

ate

Th

era

py Unadjusted P

Cumulative Probability of Death According to Treatment Group in

the Multicenter Automatic Defibrillator Implantation Trial – Reduce

Inappropriate Therapy (MADIT-RIT)

Years of Follow-up

Cu

mu

lati

ve P

rob

ab

ilit

y o

f

Death

Unadjusted P=0.03

N=21/486 (4.3%)

44%, p=0.06

N=34/514 (6.6%)

N=16/500 (3.2%)

55%, p=0.01

Moss AJ, 2012

Age 65

Duration-Delay

better

Conventional

better

Average Follow-up:

1.4 years

Age 65

High-rate

better

Conventional

better

0 0.5 1 1.5 2 2.5 3

Years since randomization

KC

CQ

Overa

ll S

um

mary

90

85

80

75

70

Average Overall Summary Score (95% CI) in the Kansas City Cardiomyopathy

Questionnaire by Treatment Status Among LBBB Patients

Veazie PJ, 2012 CRT-ICD

ICD

* * * * *

*: P

Years since randomization

Pro

babili

ty o

f H

F o

r D

eath

0 0.5 1 1.5 2 2.5 3 3.5

Unadjusted P=0.401

0.0

0.1

0.2

0.3

0.4

0.5

0.6

ICD Age

1,62

2,95

4,14

12,6

14,5

VVI DDD CRT VVI

ICD

DDD

ICD

CRT-D

9,5

Tipo di stimolatore

(€∙1

000)

124

1159

114 118

471

2167

0

500

1000

1500

2000

2500

Costo dei pacemaker, per tipo di

stimolazione, nella Regione Toscana (2012)

Spesa complessiva, per

tipo di stimolazione (AOU Careggi, 2012)

Per cortesia: Dr.ssa S. Asaro,

SOD Farmacia, AOUC Careggi

VVI: stimolatore monocamerale

DDD: stimolatore bicamerale

CRT: stimolazione biventricolare

ICD: def ibrillatore impiantabile

Device per lo SCC

Fumagalli S, 2011 Follow-up (mesi) 0 40 50 60 10 20 30

So

pra

vv

ive

nza

(%

)

0.6

0.8

0.0

0.2

0.4

1.0

HR p

Age (D·year) /

AF (Yes vs. No) 2.05 0.017

CAD (Yes vs. No) 2.55

Low Inter-

mediate

High Very

High

Mortality Risk

ICD

Recip

ien

ts (%

)

The MADIT Score

Age >70 years

NYHA Class >II

AF or atrial flutter

BUN >26 mg/dL

QRS Length >120 ms

Inappropriate ICD – 24%

Low risk: low mortality risk

Very High Risk: high risk of

nonsudden events

The National Cardiovascular Data Registry (2006-2008) – N= 44,805

Tsai V, J Am Geriatr Soc 2011

Mortalità per gruppi di età e per MADIT Score, nel

Clinical Service® Project (Medtronic, Italia)

HR=1.31, p75

Pazienti da sottoporre

ad impianto di ICD /

CRT-D

75 anni

Base

MMSE

Trail Making Test A / B

Scala HADS / SF-12

SPPB / 6MWT

+ Valutazione cardiologica standard

6-

1. Differenze età-correlate nella risposta

alla stimolazione (CRT-D vs. ICD)

2. Con la CRT-D, i pazienti più anziani

hanno una migliore risposta funzionale

rispetto agli altri gruppi di età? 3. Il profilo funzionale e le sue variazioni

influenzano la risposta alla terapia e la

prognosi dei pazienti con CRT-D?

12 mesi

Endpoint Valutazione

Una proposta di Studio …

http://aiac.it/

QoL Score

(MLWHF)

(Change)

Change

>1 NYHA

Class (%)

MIRACLE N=453, III-IV

MUSTIC SR N=58, III

MIRACLE ICD N=369, III-IV

CONTAK CD N=227, II-IV

0

-5

-10

-15

-20

80

60

40

0

(N, NYHA Class)

Improvements in health related quality of life and NYHA functional class

ranking in patients with moderate-to-severe heart failure by CRT. A review

of the results of clinical trials

CRT Control

20

Linde C et al,

2012

P

Pedersen SS, 2011

Psychotropic drugs

ICD shocks

ICD concerns

Type D personality

Smoking

Diabetes

Atrial fibrillation

NYHA III-IV

Heart failure

No partner

Age > 65

Men

2.73

7.98

2.95

1.49 (0.41-5.48)

Demographic, clinical & psychological correlates of persistent depressive

symptoms (HADS – D >8; 14%) after 3 months from ICD implantation (N=386, age: 58+12 years, LVEF

Pre-ICD

Post Implant Recovery & Adjustment

End of Life

Possible Crucial ICD

Events

Shock Worsening

Disease

Recall ICD

Complications

Trajectory of ICD

patient experiences

Dunbar SB, 2012

Symptom

stability

Symptom

frequency

Symptom

burden

Physical

limitation

HRQL Social

limitation

Overall

summary

score

Basic scales

D S

core

s (

CR

T-D

- IC

D)

5

3

1

-1

-3

0

CRT-D better

ICD better

Differences (95%CI) in the Kansas City Cardiomyopathy Questionnaire (MADIT-CRT; N=1699, Age: 64 years, EF

0 0.5 1 1.5 2 2.5 3

Years since randomization

Pro

babili

ty o

f H

F o

r D

eath

3.5

Unadjusted P=0.003

0.0

0.1

0.2

0.3

0.4

0.5

0.6

Age >75

Age

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73299

55578

47909

42701

36777

2249019450

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0

20000

40000

60000

80000

55

D Q

uali

ty a

dju

ste

d l

ife y

ears

(Q

ALY

s)

Starting Age (years)

3.16

3.62

4.084.39

4.72

4.38

5.25

6.06

6.86

7.42

4.73

5.78

6.75

7.72

8.54

0

1

2

3

4

5

6

7

8

9

Incre

men

tal C

ost

per

QA

LY

(€)

60 65 70 75

CRT + ICD (CRT-D)

CRT

Medical Therapy (MT)

55

Starting Age (years)

60 65 70 75

CRT-D vs. CRT

CRT-D vs. MT

CRT vs. MT

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

Yao G, Eur Heart J, 2007

MIRACLE – ICD (2003)

CONTAK – CD (2003)

MIRACLE – ICD II (2004)

REVERSE (2008)

-6.0 (-6.5, -5.5)

-12.0 (-12.3, -11.6)

-2.6 (-9.6, 4.4)

-1.7 (-4.5, 1.1)

Total -6.0 (-10.6, -1.5)

Favours CRT-D Favours ICD

Weighted Mean

Difference

(95% CI)

CRT-D – N=936, ICD – N=719

Age: 62-67 years; LVEF: 22-27% Follow-up: 6-12 months

Meta-analysis of included randomized controlled studies for quality

of life enrolling patients with New York Heart Association class I–IV

Minnesota Living with Heart

Failure Questionnaire (MLHFQ)

NYHA

Class III-IV

Chen S, Europace 2012

0 4 6 8 2 Years

ICD – N=409

Non ICD –

N=237

P3 RF)

Age: 59

Age: 66

Age: 74

RF: risk factor(s)

Follow-up: 7.6 years

NNT for Low & Intermediate

Risk = 6

Barsheshet A, JACC 2012

Califf RM et al., 2002

The Great Circle - a model to integrate quality measures into

the development cycle for therapeutics

Outcomes

Concept

Clinical Research

Guidelines

Quality Indicators

Performance

measures

(Education, Feedback) ?