Transcript 2 - Livemedia

ICD THERAPIES:
are they harmful or just high risk markers ?
Konstantinos P. Letsas, MD, PhD, FESC
LAB OF CARDIAC ELECTROPHYSIOLOGY
EVANGELISMOS GENERAL HOSPITAL
ATHENS
ICD therapies are common
• In a meta-analysis of 7 major ICD trials, appropriate ICD
therapy (including both ATP and shock) occurred in up to 64%
and inappropriate therapies occurred in up to 24% during 20
to 45 months of follow-up.
• Among the 194 000 patients included in the ALTITUDE
survival study, appropriate and inappropriate shock rates at
5 years were 23% and 17%, respectively.
• In MADIT-RIT, in conventional therapy arm, the incidence of
appropriate and inappropriate therapies was 22% and 20%,
respectively.
Am J Cardiol. 2006;97:1255-1261
Circulation. 2010;122:2359-2367
N Engl J Med 2012;367:2275-83.
Are ICD shocks simply a marker of risk or
the shocks themselves cause harm ???
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Shock-induced damage of the myocardium
• Experimental studies have shown that the occurrence of
biophysical injury with electrical shocks leads to
electroporation of cellular membrane and cellular necrosis
(Pakhomov et al. Arch Biochem Biophys 2007;465:109-18. Lee
• et al. Ann Rev Biomed Eng 2000;2:477-509).
Shocks after ventricular arrhythmia can contribute to
intracellular calcium overload, maintaining a vicious cycle of
• arrhythmia promotion and electrical storm (Tsuji Y, et al.
Circulation 2011;123:2192-203).
ICD shocks >9 J delivered during sinus rhythm or VF result in a
10-15% reduction in the cardiac index and increase the risk of
HF (J Cardiovasc Electrophys 1998;9:791–797).
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Shock-induced impact on mortality
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
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Figur e
vs no shock.
(C) Forest plot for hazard ratio of mortality: any shock vs no shock. (D) Forest plot for hazard ratio of mortality: eboth types of
for hazard
ratio of mortality:
2.
shock
vs
no
shock. Cl, confidence interval: CRT, cardiac resynchronization therapy; HR, hazard ratio; ICD, implantable cardioverter-
ro
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Predictors o f M o rt al it y i n P a tients W
h Ca nard i a e fibrillator: ••
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A Systematic R e v
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iew a n d M
SE
1.35.1
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Hazard Ratio
IV R ando m
ht
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Hazard Ratio
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vs. no shocks
Bhavnani 2010
Saxon CRT-D 2010
Saxon ICD 2010
van Rees 2011
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(95% C l)
Heterogeneity:
Test for overall
Wei
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effect: Z = 4.73
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3%
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1.16 [0.78, 1.72)
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--• A n y t ype
of ( a p pro p riate a n d i propriate) was an--ependent
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types of shocks showed that the
• Th e c o m p ar i s o n of
risk a s s oc i a ted w ith a p pr o p shocks (HR, 1.8
d if fem
r e nt
- •4•) was
1.35.2
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vs. no shocks
Bhavnani2010
Panotopoulos 1997
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Test for overall effect: Z = 4.79 (P < 0.00001)
1.35.3
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ap prop ria te
Saxon CR T-0
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ks
Saxon
2010
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20 1 0 (95% Cl)
Heterogen eit y: Ta u 2
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19.7%
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2.09
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0 .3 3, df
1 (P
0 .57 );
n o t s i g= n if ic a nr= ti al yted i=ff e r=e n t the mortality risk associated with
o r t ality
(HR, 1.55), electrical storm (HR, 2.4), or
f r o= mi n a p p r oZ p= r i at e
a p p ro p r i a t a n
ri a t eshocks (HR, 2.34).
s h o cks
~
d
p ri a t e
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in aa p
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op
=
=
=
=
Z
• T h e AT P th e
uring follow-up were not associated with
r a p i einscdre a sed m rt a lit y ( h i g h t o m o d confidence).
e r a te
0.0 0 ;
Ch i2
Test for ov e ral l
eff ec t:
4 .3 1 ( P <
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0 %
Any s ho cks
(A pp ro p ria te
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o r
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I napp rop ria te)
napp2010
rop ria te)
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Subtotal
(95% Cl)
Heterogeneity: Tau2
Test for ov era ll
0.761
v s. no s ho c ks
v s. n
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1 (P
eff ec t:
= 1 0.8 5
0%
1.35.6
( 3 o r more th an
(P < Elec
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01 l ) sto rm
Exner 2001
0.875
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ho u rs) (95% Cl)
Not applicable
Heterogeneity:
Test for overall effect: Z = 2.93 (P = 0.003)
-•
o s ho c
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0.104
57.2%
42.8%ks
100.0%
O. 70); 12 =
3 app r opr ia te
0.299
2.14 [1.79, 2.55)
2.03 [1.66, 2.49)
2.09 (1.83, 2.39]
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100.0%
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in 24
2.40 [1.34, 4.31)
2.40 [1.34, 4.31]
0.5
ADlbaIACeELEt al.CTCanaROPHdian
og0.2
29therapy
;2013
LAB OF CAR
YSIOLJourOGYnal, EVofANCarGELdiolI0.1
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ICD NE
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no ICD therapy
Effect of appropriate ICD Therapies on
mortality: the OMNI Trial
• For patients who experienced only appropriate therapy
compared with patients experiencing no episodes, after
adjusting for baseline predictors HR was
– 1.46 (p = 0.023) in the ATP-treated group;
– 2.11 (p < 0.001) for SSE patients;
– 2.55 (p = 0.002) for MSE patients (>1 shock).
• Thus, all groups receiving appropriate therapy had
significantly increased mortality compared to those with
no episodes.
J Cardiovasc Electrophysiol. 2016;27:192-9.
Effect of inappropriate therapies on
mortality: the OMNI Trial
• The HR for mortality for patients who experienced only
inappropriate therapy compared with patients experiencing no
episodes, after adjusting for baseline predictors, was
– 0.99 (p= 0.984) for the inappropriate ATP group;
– 1.52 (p = 0.052) for the inappropriate SSE group;
– 1.15 (p= 0.734) for the inappropriate MSE group.
• None of the groups receiving inappropriate therapy had a
significant increase in mortality compared with those with no
episodes.
J Cardiovasc Electrophysiol. 2016;27:192-9.
The shock burden
ICD shocks are associated with increased mortality risk,
and the burden of shocks plays a role in this association
•
Patients with 1–5 shock days did not
have a significantly increased risk of
death (HR 1.30), while those with 6–
10 shock days (HR 2.22) and 10 shock
days (HR 3.66) had increasingly higher
risk.
•
Likewise, patients who received one to
five total shocks did not have an
increased risk of death (HR 1.08),
while those receiving 6–10 shocks (HR
2.07), or >10 shocks (HR 2.31) had a
greater than twofold increased risk of
death as compared with patients who
received no shocks.
Heart Rhythm 2011;8:1881–1886
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Data from the MADIT-RIT trial
Circ Arrhythm Electrophysiol. 2014;7:785-792
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Data from the MADIT-RIT trial:
are ATP therapies harmful?
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Data from the MADIT-RIT trial:
are ATP therapies harmful?
• The significant reduction in appropriate and
inappropriate ATP in the high rate and delayedtherapy groups may have contributed to the
observed mortality reduction of 44 to 55% seen in
this study, and the findings raise questions about the
need for and safety of empirical ATP.
• Are ATP therapies pro-arrhythmic (AF, VT, VF)?
N Engl J Med 2012;367:2275-83.
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
All types of ICD therapies have been
associated with increased mortality
• Appropriate and inappropriate shocks
• Appropriate and inappropriate ATP therapies
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Can we uncouple the effect of
arrhythmia from the effect of therapy?
Can we uncouple the effect of
arrhythmia from the effect of therapy?
• Each VT, FVT and VF episode increased risk by 4%, 2% and
15%, respectively.
• Each episode of VT treated with ATP was associated with an
approximately 3% increased risk of death, whereas shocked
FVT increased risk by 31% and shocked VF by 16%.
• Patients who died had 5-6 times more VAs (VT,FVT,VF) than
survivors.
• Patients with more VA episodes and more shocks have
higher mortality than patients with less of both;
• Inappropriate shocked episodes were not associated with
increased mortality risk.
Sweeney MO et al. Heart Rhythm 2010;7:353–360.
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Can we uncouple the effect of
arrhythmia from the effect of therapy?
Sweeney MO et al. Heart Rhythm 2010;7:353–360.
Risk of death by VA type and therapy
• ATP-terminated VT was not associated with an increased
mortality, whereas shocks for similar arrhythmias were
associated with a worse outcome.
• This possibly indicates a direct detrimental effect of ICD
shocks on mortality.
Sweeney MO et al. Heart Rhythm 2010;7:353–360.
Does ICD therapies reduction decrease
mortality ?
• The answer should be YES…
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Impact of Programming Strategies Aimed at
Reducing Nonessential ICD Therapies on Mortality:
A Systematic Review and Meta-Analysis
• Therapy reduction programming
was associated with a significant
30% lower risk of death versus with
conventional programming.
• Similar reductions in mortality were
observed when only the 4 RT were
included (26% relative reduction).
Circ Arrhythm Electrophysiol. 2014;7:164-170
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Implantable cardioverter-defibrillator shock
prevention does not reduce mortality:
A systemic review
• The 17 trials included in this meta-analysis
enrolled a total of 5875 patients.
– 9 antiarrhythmic medications studies included 2428
patients
– 3 catheter ablation studies enrolled 256 patients
– 5 ICD programming studies enrolled 3191 patients.
Heart Rhythm 2012;9:2068–2074
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Effect of interventions on ICD shocks
• Antiarrhythmic medications and catheter ablation of
VT significantly reduced the number of patients
receiving shocks by 41% (OR 0.59) and 65% (OR 0.35),
respectively.
• Of the ICD programming trials, only the PAINFREE-II
(Pacing Fast Ventricular Tachycardia Reduces Shock
Therapies) trial demonstrated a significant reduction
in shocks (OR 0.38).
Heart Rhythm 2012;9:2068–2074
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Study
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OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITALfa, vAoTuHrsEN S
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ICD shocks are simply an adverse prognostic
marker: limitations of the studies
• The lack of survival benefit observed with these therapies could
suggest that ICD shocks are simply an adverse prognostic
marker and that they do not contribute to the increased risk of
• death among patients experiencing shocks.
Most of the trials included in this review had a mean follow-up
of only 1 to 2 years. This may be too short to observe a
reduction in mortality, particularly for interventions such as
• catheter ablation, which have early,periprocedural risks.
Overtime, repeated ICD shocks can produce cumulative
injury;explanation
thus,the mortality
of preventing
• myocardial
Another possible
for the benefits
lack of survival
benefit in
ICD
shocks
more manifest
as time passes.
these
trials could
is the be
relatively
modest reduction
in ICD shocks
that was achieved.
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
ICD shock is the innocent bystander in the
equation and not the guilty suspect
• Inappropriate shocks associated with AF or atrial flutter
increase mortality, whereas inappropriate shocks
associated with sinus tachycardia, artifacts, or noises were
not associated with increased mortality (J Am Coll Cardiol
2013;62:1674-9).
• ICD shocks delivered after noninvasive electrophysiological
study were not associated with an increase in mortality
compared with shocks occurred after spontaneous VT/VF
(Heart Rhythm 2010;7:755-60).
•
This evidence supports the concept that it is the condition
underlying the myocardium and not the shock that causes
damage.
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
The occurrence of appropriate or inappropriate
shocks may be a marker of HF progression:
Data from the SCD-HeFT and MADIT II trials
• Thirty percent of deaths occurred within 24 h of an appropriate
shock, a sign of impending death.
• The most common cause of death during follow-up among shock
recipients was progressive HF.
• The risk of first and recurrent HF hospitalization increased by 90%
and 74%, respectively, after appropriate shocks.
• Triggers for ventricular arrhythmias include myocardial ischemia,
catecholamines, electrolyte abnormalities, and ventricular
remodeling.
• These arrhythmogenic factors can be precipitated by the onset of
HF decompensation. The same factors can cause AF either causing
or worsening HF.
N Engl J Med 2008;359:1009 –1017.
Circulation 2006;113:2810 –2817.
Anxiety and stress following ICD shocks
• Patients with ICD shocks have increased levels of
psychological distress, anxiety, anger, post-traumatic
stress disorder, and depression as compared with
patients who do not receive shocks, and these
psychological sequelae may be a contributing factor to
the increased mortality seen in patients who receive
ICD shocks.
Int J Cardiol 2011; 147:420–423
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
ICD THERAPIES:
are they harmful or just high risk markers ?
• Both answers are possibly correct.
• ICD therapies themselves are likely to only be
partially responsible for the increased mortality
associated with their use, and that therapies
themselves are often a marker for more severe
cardiac disease.
EHRA Young EP Group
European Society of Cardiology
• The Young Electrophysiologists Committee has been
formed by EHRA to facilitate, enhance and accelerate
the development of early career electrophysiologists.
• Electrophysiologists until the age of 40 or those older
than 40 but no more than 3 years out of training are
directly targeted by this new EHRA initiative.
• Apply for EHRA young EP Group at :
https://www.formstack.com/forms/escardioehra_young_ep_data
LAB OF CARDIAC ELECTROPHYSIOLOGY , EVANGELISMOS GENERAL HOSPITAL , ATHENS
Networking and education among
Young EPs across all countries
• We are planning to promote networking and education among
Young EPs across all member countries.
• Requirements in your country to have a Young EP come for a
1-2 week observership in a particular centre.
• Potential centres that would have a Young EP contact and
would be willing to accept other members of the Young EP
community for a 1-2 week observership.
• Strengths/skills of each centre.
• If there are particular “extra” requirements for a particular
centre, the Young EP contact there should specify it.
Thank you very much for your attention