Date post: | 22-Jan-2016 |
Category: |
Documents |
Upload: | michael-hood |
View: | 214 times |
Download: | 0 times |
Dr. Maurizio GaspariniDr. Maurizio Gasparini UO Elettrofisiologia ed ElettrostimolazioneUO Elettrofisiologia ed Elettrostimolazione
Istituto Clinico HumanitasIstituto Clinico Humanitas,, IRCCS, Rozzano-Milano IRCCS, Rozzano-Milano
ADVANCES IN CRT ADVANCES IN CRT
What Is The Patient Profile Who What Is The Patient Profile Who Can Benefit from CRT-P only? Can Benefit from CRT-P only?
Progressi nella CRTProgressi nella CRT
Quale è il profilo del paziente che può Quale è il profilo del paziente che può beneficiare della sola CRT ?beneficiare della sola CRT ?
Eur Heart J 2007; 28: 2256-95Eur Heart J 2007; 28: 2256-95
Cardiac resynchronization therapy Cardiac resynchronization therapy guidelines published for the first time in 2007 guidelines published for the first time in 2007 ……
Few months later , American GL Few months later , American GL published…published…
So very simple and clear indications So very simple and clear indications for CRT-P in HF patients !for CRT-P in HF patients !
Thank you for your attention Thank you for your attention
NYHA III-IV pts on OPTNYHA III-IV pts on OPT
LV EF LV EF << 35% 35%
QRS ≥ 120 msecQRS ≥ 120 msec Sinus rhythmSinus rhythm
However reading carefully…. However reading carefully….
The ESC and AHA/ACC/HRS Guidelines on indications for The ESC and AHA/ACC/HRS Guidelines on indications for device therapydevice therapy do not clearly indicate which patients are do not clearly indicate which patients are candidates tocandidates to CRT-P onlyCRT-P only
Solved dilemma by recent HF Solved dilemma by recent HF Guidelines ??!!Guidelines ??!!
……Once Once againagain
On the other hand,On the other hand, following GL in the clinical following GL in the clinical practice, it is mandatory to control if in the practice, it is mandatory to control if in the same field (i.e. ICD therapy) some other same field (i.e. ICD therapy) some other guidelines existguidelines exist ::
in patients within patients with severely compromised severely compromised left ventricular functionleft ventricular function
regardless of underlyingregardless of underlying etiologyetiology… …
in primary as well as in secondary in primary as well as in secondary preventionprevention
as clearly demonstrated by several studiesas clearly demonstrated by several studies
ICDICD therapy has been demonstrated to be therapy has been demonstrated to be particularly effective in preventing sudden particularly effective in preventing sudden cardiac death (SD) and thus reducing total cardiac death (SD) and thus reducing total mortality :mortality :
COMPANIONIsch/non EF ≤ 35%; NYHA III- IV; CRT-D mortality by 36%
NE
JM 2
004;
350:
2140
-50
SCD-HeFTIsch/non isch;EF ≤ 35%; NYHAII-III ICD mortality by 23%
NE
JM 2
005;
352:
225-
37
NE
JM 2
004;
350:
2151
-8
DEFINITENon isch DCM; NYHA I/III; EF Non isch DCM; NYHA I/III; EF ≤ 36%; ICD mortality by 35%
MADIT IIPost-MI, FE ≤ 30%, any NYHAICD mortality by 31%
NE
JM 2
002;
346
(12
); 8
77-8
3
ICD decreases total mortality in pts with systolic dysfunction of any etiology regardless NYHA functional class
How to combine both these 2 statements?
85% of CRT
candidates are in
NYHA III !!
Maurizio Gasparini Istituto Clinico Humanitas - Rozzano, Milano
(Italy)
Long-term follow up after cardiac Long-term follow up after cardiac resynchronization therapy: resynchronization therapy: poor clinical outcome in patients poor clinical outcome in patients enrolled in advanced NYHA class IVenrolled in advanced NYHA class IV
Presented at AHA Congress 2003 Published on theHeart.org
268 268 consecutiveconsecutive CRT pts CRT pts
October 1999 / July 2003October 1999 / July 2003
NYHA II: 34 pts (13%)NYHA II: 34 pts (13%)
NYHA III: 194 pts (72%)NYHA III: 194 pts (72%)
NYHA IV: 40 pts (15%)NYHA IV: 40 pts (15%)
Kaplan Meier survival estimatesaccording to NYHA at baseline
follow-up time (months)0 6 12 18 24 30 36
0.00
0.25
0.50
0.75
1.00nyha 2
nyha 3
nyha 4
.00.0011
H.R. 3-4 = 1.7H.R. 3-4 = 1.7
H.R. 2-4 = 4.5H.R. 2-4 = 4.5
Log rank p= .002Log rank p= .002
Total mortality rate according to NYHA class at baselineTotal mortality rate according to NYHA class at baseline
.04.04
.0.011
m.r. 0%
m.r. 5.7%
m.r. 16.6%
NYHA IV: 40 pts
33 pts IV33 pts IV
No ev amine
No mechanical ventilation
7 pts IV advanced
4 ev amine + mech. vent
3 ev amine no mech. vent
deaths :3/33 deaths :5/7
NYHA IV pt into details :NYHA IV pt into details :
Kaplan Meier cardiac survival estimates according to NYHA at baseline
follow-up time (months) 0 6 12 18 24 30 36
0.00
0.25
0.50
0.75
1.00 nyha 2
nyha 3
nyha 4
Advanced nyha 4
Cardiac mortality rate according to NYHA class at baseline
Log rank p= .00001
ns
.02
All p= .00001
Non advanced NYHA IV survival rate:similar to NYHA III !!
ns
m.r. 0%m.r. 4.7%
m.r. 7.8%
m.r. 80.8%
Which pts are candidates to CRT-P only ??
So ambulatory NYHA IV behaviour is like NYHA III patients
Which data in the literature?
Clealand NEJM 2005
Care HF
CRT-P 37% mortality with respect to OPT
Bristow NEJM 2004
COMPANION:Risk of secondary endpoint
death from any cause 24 % CRT (p=0.059) vs OPT 36 % CRT-D (p=0.003) vs
OPT
Inclusion criteria :
NYHA III-IV, EF< 35%, QRS > 120
191 pts CRT-D
120 primaryprevention
71 secondary prevention
Results ( fu:2 yrs):
• at least 1 appropriate therapy
35% secondary prevention
21% primary prevention
• No predictors
All cause mortality reduction by 17%
Sudden death reduction by 96%
1303 pts
4 European Centers
MILOS STUDY
Data from metanalisis
ICD with respect to OPT mortality by 31%
CRT-P with respect to OPT mortality by 34%
CRT-D with respect to OPT mortality by 43% Further 9% of mortality reduction with CRT-D!!!
IBIB IA IA IA even in the upcoming European IA even in the upcoming European
GLGL
Which is the behaviour in real world ?
1303 pts
Progressive dramatic increase in % of CRT-D in Europe !!
CRT-D allows all cause mortality reduction by 17%
Avg = 88Avg = 76
USAItaly
NetherlandsGermanyBelgium
DenmarkAustria
SwedenWestern Europe
FranceUK
SwitzerlandNorwayIrelandSpain
PortugalFinland
0 50 100 150 200 250 300
CRT-D CRT-P 2007 WE Average 2006 WE Average
CRT-P
Similar behaviour in USA
(small rate of CRT-P implant with respect to CRT-D)
disadvantages of CRT-D systems in CRT disadvantages of CRT-D systems in CRT candidatescandidates
Aside from costs considerationsAside from costs considerations
1) No significant increased risk of 1) No significant increased risk of complications (implant - related)complications (implant - related)
2) No significant increased complications 2) No significant increased complications during follow upduring follow up
If ICD back up seems reasonable… we should If ICD back up seems reasonable… we should consider the possibility of….consider the possibility of….
No major technical differences between CRT and CRT D implantation
1 a1 a ComplicationsComplications ((COMPANION trial, Bristow et al., NEJM 2004)COMPANION trial, Bristow et al., NEJM 2004)
ParameterParameter OPTOPT
n=308n=308
OPT +OPT +CRTCRT
n=617n=617
OPT + OPT + CRT-DCRT-D
n=595n=595
Implant Success (%)Implant Success (%) –– 88.388.3 92.092.0
Total Implant Time (minTotal Implant Time (minSD)†SD)† –– 200200
116116
213213
131131
Moderate or Severe Adverse Events (% Moderate or Severe Adverse Events (% of total patients)of total patients)
5555 5858 6060
30 day crude mortality (%), from 30 day crude mortality (%), from randomization or implantationrandomization or implantation
1.01.0
{–}{–}
1.81.8
{2.1}{2.1}
0.90.9
{0.7}{0.7}
Absolutely Absolutely no differences in severe implant-related in severe implant-related adverse events between device typeadverse events between device type adverse events adverse events are mainly associated to LV lead positioning...are mainly associated to LV lead positioning...
1 b Complications related to defibrillation testing (DT)1 b Complications related to defibrillation testing (DT)1) DFT can be avoided
2) DFT can be safely delayed
So…at this point … which arguments for So…at this point … which arguments for not associate ICD function to CRT-P?not associate ICD function to CRT-P?
The CARE-HF The CARE-HF && CARE-HF extension phase data CARE-HF extension phase data
It has been postulated that It has been postulated that CRT-P per se CRT-P per se mortalitymortality due to due to sudden deathsudden death … …
…especially in the “long term” f.u. …especially in the “long term” f.u.
COMPANION - Bristow NEJM 2004;350:2140-50
Scissors CRT-P / OPT at 240 days
Scissors CRT-D /CRT at 120-240 days
CompanionCompanion Does CRT-P really Does CRT-P really sudden sudden
death ?death ?
Mean f.u. = 29,4
months
NEJM 2005;352:1539-49
Care HFCare HF
CRT-P diverges from OPT only at 240 days !!
Clealend NEJM 2005
COMPANION - Bristow NEJM 2004
COMPANION: same behaviour of CRT-P of
CARE-HF !!!!
Between day 120 and 240 gg CRT-D begins to saves lifes……
The identical behaviour is The identical behaviour is based on based on the the typical temporal pattern typical temporal pattern of of thethe “reverse “reverse remodeling”remodeling” processprocess conferred by CRT conferred by CRT……
0
10
20
30
40
50
60
1 2 3 4 5 6
Lef
t ve
ntr
icu
lar
ejec
tio
n
frac
tio
n (
%)
-15
-10
-5
0
5
1 2 3 4 5 6
Left
Ven
tric
ular
End
Dia
stol
ic
Dia
met
er C
hang
e (%
)
Baseline 6 12 24 36 48 mos Baseline 6 12 24 36 48
mos
SR
AF + AVJ Ablation
AF no AVJ Ablation
(Gasparini et al., JACC 2006)
Mode of death in CRT-PMode of death in CRT-P
SD in HF patients treated with CRT-P
COMPANIONCOMPANION
CARE-HFCARE-HF
OPTOPT CRT-PCRT-P
Sudden death21%
CHF47%
Other32%
Sudden death32%
CHF45%
Other22%
2 different studies 2 different studies with SAME CRT-P with SAME CRT-P curve behaviourcurve behaviour
-with SAME SD % in -with SAME SD % in CRT-PCRT-P
1/3 pts die for SD1/3 pts die for SDin CRT-Pin CRT-P
What about the earlier phases of CRT when What about the earlier phases of CRT when reverse remodeling has still to take place?reverse remodeling has still to take place?
SCD in HF patients treated with CRT
Would you take the Would you take the CRT leap…CRT leap…
With a parachute With a parachute (ICD)(ICD)
or without a or without a parachute… parachute…
1)1) Would it be worthwhile to stratify Would it be worthwhile to stratify arrhythmic risk?arrhythmic risk?
(“ethical” issue this day and age)(“ethical” issue this day and age)
2) Simply implant a CRT-D 2) Simply implant a CRT-D system !!system !!
COMPANION
6 mos Benefits from ICD back up to protect from SD between 120 and Benefits from ICD back up to protect from SD between 120 and 240 days after CRT clearly demonstrated by Care HF and 240 days after CRT clearly demonstrated by Care HF and Companion Companion
CARE HFJohn G.F. ClelandN Engl J Med 2005;352:1539-49
CARE HF extension phaseJohn G.F. Cleland
EHJ (2006) 27, 1928–1932
Mean f.u. = 37,4 months
Mean f.u = 29,4 months
Does Does really really CRT-P CRT-P sudden death in sudden death in the long term follow up ?!the long term follow up ?!
Mean f.u = 29,4 months
CAREfully looking inside CARE HF extended
At the end of the study:
n of deaths:
200 pts
Due to the demonstrated benefit of CRT-P CRT-P strongly recommanded at the end of CARE HF for pts randomized in OPT group
Recommendation letterRecommendation letter• CRT-P strongly recommended at the end of
CARE HF for pts randomized in OPT group !!!!
However…..
Optimal drug therapy
404 pts / 154 deaths:
CRT
409 pts / 101 deaths:
• Risk reduction of death from HF by 45% ( HR = 0,55)
32%35%
• Risk reduction of death from SCD by 46% ( HR = 0,54)
statistically significant and statistically statistically significant and statistically correct…correct… but clinically but clinically
uncorrect…uncorrect…
DoesDoes really really CRT-P CRT-P sudden death in the long term sudden death in the long term f.u.? f.u.?
Why such a big Why such a big spaceball ?! spaceball ?!
CARE HF extended
Mean f.u. = 37,4 months
8 months longer than CARE HF… BUT CONSIDER that n of pts is LOWER due to the 200 deaths..
Considering pts still alive… for them LONGER f.u (~ 10 months) WITHOUT protection of CRT: ETHICAL ???
CAREfully looking inside CARE HF extended
SDOPT: 54/404 (13.4%) 4.3% / y
2.5%
1 yr
2.5%
2 yr 3 yr
2.5%
CRT: 32/409 (7.8%) 2.5%/y SD: 32% in CRT
2.5%
4 yr
2.5%
1 yr
2.5%
2 yr 3 yr
8 %8%
4 yr
CAREfully looking inside CARE HF extended
CRT arm
409 pts
82 † (29.4 months) 20% mortality
102 † (37.4 months) 25% mortality
OPT arm
404 pts
120 † (29.4 months) 29.7% mortality
154 † (37.4 months) 38% mortality
95 OPT CONVERTED to CRT:22 † 23.2% mortalityBUT…404 pts
42.7% mortality
309 pts: 132 † (DESPERATE OPT!!)
DESPERATE OPT
CARE HF investigators postulated that CRT-P SCD during long term f.u
but SD rate in CRT-P REMAIN THE SAME over time !!
Pts left on OPT (despite recommendations!) continues to dramatically die like flies… that the only reason for
the supposed reduction of SD with CRT !!!If CRT-P would protect from SD this would be the pattern
of the survival curve
I honestly think that it is not true
In conclusions….In conclusions….1) 1) CRT-DCRT-D undeniably reduce mortality with respect to undeniably reduce mortality with respect to OPTOPT
2) All studies comparing CRT-P and 2) All studies comparing CRT-P and CRT-D, CRT-DCRT-D, CRT-D armarm has shown greater benefit with respect to CRT-P in has shown greater benefit with respect to CRT-P in terms of SD reductionterms of SD reduction
4) We should offer to any HF pt the best possible 4) We should offer to any HF pt the best possible therapy, i.e complete therapy therapy, i.e complete therapy CRT-DCRT-D
5) Last but not least, more than 85% of CRT candidates 5) Last but not least, more than 85% of CRT candidates satisfy a class satisfy a class IAIA indication for ICD !!! indication for ICD !!!
3) Metanalisys data undeniably shown that CRT-D 3) Metanalisys data undeniably shown that CRT-D saves more lives than CRT-P (9% more!!)saves more lives than CRT-P (9% more!!)
Is there still place for CRT-P ?Is there still place for CRT-P ?
CRT-P FOR WHOM?
considerconsider
1) LIFE EXPECTANCY1) LIFE EXPECTANCY if life expectancy < 1 yrif life expectancy < 1 yr
Aim of the intervention: Aim of the intervention: QOL for the remaining life QOL for the remaining life
very advanced anagraphic age (at least > 80 years)very advanced anagraphic age (at least > 80 years)
very advanced biological agevery advanced biological age
Reasonable NOT to provide an ICD back-upReasonable NOT to provide an ICD back-up
due to severe comorbidities due to severe comorbidities cachexiacachexia
neurological diseasesneurological diseases severe COPD / severe renal/epatic insufficiencysevere COPD / severe renal/epatic insufficiency
complicated insulin dependent diabetescomplicated insulin dependent diabetes peripheral vascular diseaseperipheral vascular disease
2) PREVIOUS VVI or DDD PM CAUSING “IATROGENIC” LV DYSFUNCTION at a reasonably 2) PREVIOUS VVI or DDD PM CAUSING “IATROGENIC” LV DYSFUNCTION at a reasonably advanced age (>75 yrs)advanced age (>75 yrs)
Often rapid clinical /echo improvement after upgrading to CRT-POften rapid clinical /echo improvement after upgrading to CRT-P
Not infrequent venous access difficulties in those settingsNot infrequent venous access difficulties in those settings
A rapid response after CRT may reduce the arrhythmic risk A rapid response after CRT may reduce the arrhythmic risk
Increased risks of complications if LV lead Increased risks of complications if LV lead AND AND RV defib coil insertion necessaryRV defib coil insertion necessary
3) PREVIOUS DDD pm with two unipolar leads3) PREVIOUS DDD pm with two unipolar leads
Unipolar lead
Unipolar lead
PM DDD
Risk/benefit ratio evaluation-> which is better : CRT-D with 3 Risk/benefit ratio evaluation-> which is better : CRT-D with 3 more leads or CRTP with only one more LV lead ???more leads or CRTP with only one more LV lead ???
CS lead
Subclavian vein occlusion is not an unusual finding after lead insertion
Collateral vessels
Collateral vessels
Subclavian vein occlusion
Mr. A.I. After Mr. A.I. After 17 years17 years of device history… of device history…
1994: VVI1994: VVI
1996: DDD1996: DDD
1989: Epi-ICD1989: Epi-ICD
1997: ICD-DDD1997: ICD-DDD
2003: CRT-D2003: CRT-D
Lead burden of the VentricleLead burden of the Ventricle Subclavian vein occlusionSubclavian vein occlusion
The problem of lead burden” is not uncommon… and The problem of lead burden” is not uncommon… and upgrading from CRT-P to CRT-D may involve technical upgrading from CRT-P to CRT-D may involve technical problemsproblems
After several decubitus, lead surgical extraction… and After several decubitus, lead surgical extraction… and right sided new implant right sided new implant
New ICD
New RV lead
New RA lead
New LV epi lead
CONCLUSIONSIn summary, aside from costs considerations
indication to CRT-P should be limited to life expectancy < 1 yrlife expectancy < 1 yr (advanced age, comobidities) (advanced age, comobidities)
HF due to iatrogenic asynchronous RV pacingHF due to iatrogenic asynchronous RV pacing
difficult venous accessdifficult venous access
Since all patients eligible for CRT presentSince all patients eligible for CRT present aa CLASS IACLASS IA indication for an ICD deviceindication for an ICD device
New technology to contain costsNew technology to contain costs
InSync III Protect: InSync III Protect:
a full-feature Cardiac Resynchronization System + a full-feature Cardiac Resynchronization System + “simplified programmable “ICD“simplified programmable “ICD
allows to reduce costs by around allows to reduce costs by around 30-40%30-40%
(240)
Shocks 1 ATP + Shocks
Protect RescueSetProtect RescueSetTMTM
VF/VT treatment window: 270, 300, 330 (nom.), VF/VT treatment window: 270, 300, 330 (nom.), 360, 400 ms360, 400 ms
VT monitor only window: 370 ms (fixed)VT monitor only window: 370 ms (fixed)
400
Results Results (Recorded episodes)(Recorded episodes)
Total episodes recorded on device memory
884in 126 patients
330 episodes 554 episodes
20 INAPP. episodes
310 APP. episodes
242 INAPP. episodes
312 APP. episodes
PROTECTPROTECT CONTROLCONTROL
RELEVANTRELEVANT
Dramatically lower inapp. detections in Dramatically lower inapp. detections in PROTECTPROTECT
SameSame number of number of appropriate detectionsappropriate detections
RELEVANT StudyRELEVANT StudyPrincipal investigator: M GaspariniPrincipal investigator: M Gasparini
Presented at HRS 2008Presented at HRS 2008