scc: ‘device’ utili anche nell’anziano? - sigg...inappropriate therapy (madit-rit) atp:...
TRANSCRIPT
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SCC: ‘device’ utili anche nell’anziano? Stefano Fumagalli
Aritmologia Geriatrica, SOD Cardiologia e Medicina Geriatrica,
AOU Careggi e Università di Firenze
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SCC: ‘device’ utili anche nell’anziano?
La terapia di resincronizzazione
cardiaca (CRT)
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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
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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
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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
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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%
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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
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Class III – CRT IS NOT recommended for patients
…
1. … with NYHA class I or II symptoms and non-
LBBB pattern (QRS duration
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SCC: ‘device’ utili anche nell’anziano?
Il defibrillatore impiantabile (ICD)
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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
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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
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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
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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
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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
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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
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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
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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
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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/
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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
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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
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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
-
79827666753872437139
73299
55578
47909
42701
36777
2249019450
180171642715805
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
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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) ?