Transcript N Engl J Med

Device Therapy
In tachyarrhythmia and prevention of
sudden cardiac death
MAHDY HASANZADEH, MD
Interventional Electrophysiologist
MUMS-CRC
OCT.2011
Cardiac Devices
• Designed to:
– Restore or maintain a rhythm and rate sufficient to
meet metabolic needs
– Provide diagnostic information about
• Device operation
• The patient
3
Cardiac Devices
• Pacemakers or Implantable Pulse
Generators (IPG)
–
–
–
–
–
Provide a rate to support metabolic needs
Provide various diagnostics
Single and dual chamber
About 8-10 years longevity
Some of the newer pacemakers include
therapies which pace-terminate AT/AF
4
Cardiac Devices
• Implantable Cardioverter Defibrillators (ICDs)
– Restore sinus rhythm in the presence of
tachycardia
• Defibrillate
• Cardiovert
• Anti-Tachy Pace (ATP)
– Provide a rate to support metabolic needs
• Includes single or dual chamber pacing
– Provide various diagnostics
– 5About 6-9 years longevity
Cardiac Devices
• Cardiac Resynchronization Therapy (CRT)
– IPG with CRT, or an IPG + ICD with CRT
– Restore ventricular synchrony
• Uses a specially designed lead placed usually on the posterior-lateral
wall of the LV via the Coronary Sinus circulation
• LV epicardial lead placement is an option
• Provides RV and LV synchronous pacing
– May restore rhythms in presence of lethal tachycardia
• CRT pacing +ICD (High-Power CRT)
– Provides a rate to support metabolic needs
• CRT pacing only (Low-Power CRT)
– Provides various diagnostics
6
Cardiac Devices
• Implantable Loop
Recorders (ILR)
– Provides rate-based monitoring
• Fast rates
• Slow rates
– Provides EGM during patient
triggered events
7
Indications
Pacemakers
• The AHA and ACC have defined the indications for
pacing by the underlying arrhythmia
• Very detailed, but to simplify:
– Symptomatic bradycardia refractory to any treatment
– Typical diagnoses:
•
•
•
•
•
Sinus Node Disease (SND), or Sick Sinus Syndrome
Complete Heart Block
Chronotropic Incompetence
Vaso-vagal syncope
Carotid sinus hypersensitivity
– Usually excludes “low grade” blocks (Mobitz I and 1st degree)
8
Indications
Defibrillators
• Primary vs. Secondary Prevention for SCA
– Secondary
• Patients who have experienced a previous SCA or ventricular
arrhythmia
• Studies such as AVID1, CIDS2, CASH3 support the use of
ICDs in this population
– Primary
• Patients who have not previously experienced SCA/VA, but
are at risk
• Studies, such as MADIT II4 and SCD-HeFT5, have
demonstrated the use of ICDs in these patients
9
Indications
Defibrillators (cont.)
Well defined by Heart Rhythm Society (HRS) and include:
• Cardiac Arrest
–
–
•
Syncope of undetermined origin with:
–
•
Coronary disease or prior MI and LV Dysfunction
Inducible VF or sustained VT (non-suppressible by antiarrhythmic drugs)
Spontaneous sustained VT
–
10
Sustained VT or VF induced during EP
Nonsustained VT with:
–
–
•
Due to VT or VF, not transient or reversible
Spontaneous sustained VT with structural heart disease
Not amenable to other treatments
Indications
Defibrillators (cont.)
•
ICD Class I Recommendation
• Patients at least 40 days post-MI
•
•
LVEF ≤ 30 – 40%
NYHA class II or III
• Non-ischemic patients
•
•
LVEF ≤ 30 – 35%
NYHA class II or III
• Patients at risk of SCA due to genetic disorders
•
•
•
•
Long QT syndrome
Brugada syndrome
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular dysplasia (ARVD)
Note: This list includes the current major indications for an ICD
11
Indications
Cardiac Resynchronization Therapy
• NYHA Class III or IV heart failure
• On optimal medical therapy
• QRS > 120 ms wide
– Or Echo evidence of ventricular dyssynchrony
• Ejection Fraction of < 35%
• Who are candidates for an ICD with CRT, and who
for an IPG with CRT?
– Most get an ICD with CRT (also called “High-Power
CRT”) because of the risk of SCD in patients with LV
dysfunction
12
Sudden cardiac death(SCD)
Introduction
• Sudden cardiac death (SCD) is used to
describe cardiac arrest with cessation of
cardiac function, whether or not
resuscitation or spontaneous reversion
occurs
• Patients who do not die after cardiac arrest
should be said to have experienced aborted
SCD
Sudden cardiac death(SCD)
Definition by WHO
• Sudden collapse of cardiac function
occurring within one hour of symptoms
Sudden cardiac death(SCD)
Pathophysiology
• The vast majority of cases of SCD are due to
ventricular arrhythmias
• Ventricular tachycardia (VT) or ventricular
fibrillation (VF) account for the majority of
episodes
• This almost always occurs in the setting of
underlying myocardial disease
• More than 80% of SCD events occur in
individuals with coronary artery disease (CAD)
SCD & ischemic heart disease
• 65 to 70 % of SCDs are attributable to CAD
• SCD accounts for 30 to 50 % of coronary
deaths
• A peak incidence of VT and VF within the
first 48 hours after acute MI has also been
noted in other reports
SCD & ischemic heart disease(2)
Incidence of VT and VF after STelevation MI
• VF:4.2 %
• VT:3.5 %
• Both VF and VT:2.7 %
• 80 to 85 % of these arrhythmias occurred in
the first 48 hours.
Treatments to Reduce Sudden Cardiac Death
Correcting Ischemia
– Revascularization
– Beta-blocker
Preventing Plaque Rupture
– Statin
– ACE inhibitor
– Aspirin
Stabilizing Autonomic
Balance
– Beta-blocker
– ACE inhibitor
Improving Pump Function
– ACE inhibitor
– Beta-blocker
Prevention of Arrhythmias
– Beta-blocker
– Amiodarone
Terminating Arrhythmias
– ICDs
– AEDs
Prevent Ventricular Remodeling
and Collagen Formation
– Aldosterone receptor blockade
Implantable Cardioverter Defibrillator
First-line therapy for patients at risk for VT/VF
• Small devices, pectoral
implant site
• Transvenous, single incision
• Local anesthesia; conscious
sedation
• Short hospital stays
• Few acute complications
• Perioperative mortality < 1%
• Programmable therapy options
• Single- or dual-chamber therapy
• Battery longevity up to 9 years
ICD Mortality Benefits
in Primary Prevention Trials
% Mortality Reduction w/ ICD Rx
80
75%
73%
Overall Death
Arrhythmic Death
61%
60
55%
54%
40
31%
20
0
MADIT
1
27 Months
1
MUSTT
2
39 Months
MADIT-II
3, 4
20 Months
Moss AJ. N Engl J Med. 1996;335:1933-40.
Buxton AE. N Engl J Med. 1999;341:1882-90.
3 Moss AF. N Engl J Med. 2002;346:877-83.
4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002.
2
Secondary Prevention of SCD-Conclusions from Three RCT’s
• The ICD is first-line therapy for patients with
hemodynamically-compromising primary
ventricular tachyarrhythmias (relative mortality
reduction of 27% compared to medication).
• Benefit of ICD mainly with EF<35%, and is
independent of beta blocker use.
• Further study is required to assess the costefficacy of the ICD in other patient subsets
(EF>35%, well-tolerated VT, secondary VT/VF).
% Mortality Reduction w/ ICD Rx
Mortality Benefits with ICD Therapy
80
60
75%
76%
Arrhythmic Death
61%
55%
54%
31%
40
ICD mortality
reductions in primary
prevention trials
are equal to or greater
than those in secondary
prevention trials.
20
0
MADIT
1
27 months
% Mortality Reduction w/ ICD Rx
Overall Death
MUSTT 2
39 months
MADIT-II 3, 4
20 months
80
56%
60
40
59%
31%
Overall Death
Arrhythmic Death
33%
28%
20%
20
1
Moss AJ. N Engl J Med. 1996;335:1933-40.
Buxton AE. N Engl J Med. 1999;341:1882-90.
3 Moss AJ. N Engl J Med. 2002;346:877-83
4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions,
Late Breaking Clinical Trials, March 19, 2002.
5 The AVID Investigators. N Engl J Med. 1997;337:1576-83.
6 Kuck K. Circ. 2000;102:748-54.
7 Connolly S. Circ. 2000:101:1297-1302.
2
0
AVID 5
3 Years
CASH
3 Years
6
CIDS
3 Years
7
Major Implantable Cardioverter-Defibrillator
Trials for Prevention of Sudden Cardiac
Death
Trial
Year
Patients
(n)
LVEF
Additional Study
Features
Hazard
Ratio*
95% CI
p
MADIT I
1996
196
< 35%
NSVT and EP+
0.46
(0.26-0.82)
p=0.009
MADIT II
2002
1232
< 30%
Prior MI
0.69
(0.51-0.93)
p=0.016
CABG-Patch
1997
900
< 36%
+SAECG and CABG
1.07
(0.81-1.42)
p=0.63
DEFINITE
2004
485
< 35%
NICM, PVCs or NSVT
0.65
(0.40-1.06)
p=0.08
DINAMIT
2004
674
< 35%
6-40 days post-MI
and Impaired HRV
1.08
(0.76-1.55)
p=0.66
SCD-HeFT
2006
1676
< 35%
Prior MI of NICM
0.77
(0.62-0.96)
p=0.007
AVID
1997
1016
Prior cardiac
arrest
NA
0.62
(0.43-0.82)
NS
CASH†
2000
191
Prior cardiac
arrest
NA
0.766
‡
1-sided
p=0.081
CIDS
2000
659
Prior cardiac
arrest, syncope
NA
0.82
(0.60-1.1)
NS
* Hazard ratios for death from any cause in the ICD group compared with the non-ICD group. Includes only ICD and amiodarone patients from CASH.
‡CI Upper Bound 1.112 CI indicates Confidence Interval, NS = Not statistically significant, NSVT = nonsustained ventricular tachycardia, SAECG = signal-averaged
electrocardiogram.
Epstein A, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. J Am Coll Cardiol 2008; 51:e1–62. Table 5.
SCD Prevention Trials
• Antiarrhythmic Vs. Implantable Defibrillator (AVID) [N
Engl J Med 1997;337:1576-1583.]
• Multicenter Unsustained Tachycardia (MUSTT) Trial [N
Engl J Med 1996; 1747S-51S]
• Multicenter Automatic Debrillator Implantation (MADIT
II) Trial [N Engl J Med 2002; 346: 877-83.]
• Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
[NEJM 2005;352:225]
• Comparison of Medical Therapy, Pacing and Defibrillation
in Heart Failure Trial (COMPANION) [N Engl J Med.
2004;350:2140-2150]
AVID
(Antiarrhythmic Vs. Implantable Defibrillator)
• Purpose: to compare the efficacy of ICD versus
antiarrhythmics in patients who survive life-threatening
ventricular arrhythmias.
• Inclusion:
– Patient rescustitated from near fatal VF
– Patients who have undergone CV from sustained VT
with syncope
– Or Patients who have undergone CV from sustained VT
with severe cardiac symptoms with EF of ≤ .40.
• Primary endpoint: overall mortality.
AVID
Screened for participation = 5,989
excluded = 1,368
Registry = 4,621
Randomized = 1,016
Discharged with amiodarone
or an ICD = 970
Amiodarone ICD
(486)
(484)
Not Randomized = 2,101
Discharged with amiodarone,
an ICD, or neither = 1,931
Amiodarone
(658)
Adapted from: Exner DV, et al. J Am Coll Cardiol 1999; 34:325-333.
ICD
(861)
Neither
(412)
AVID Results
Year
ICD survival AAD survival Reduction in
(%)
(%)
mortality
1
89.3
82.3
39±20
2
81.6
74.7
27 ±21
3
75.4
64.1
31 ±21
N Engl J Med 1997;337:1576-1583
Multicenter Unsustained Tachycardia (MUSTT)
Trial
• Hypothesis: Antiarrhythmic therapy guided by EP testing
can reduce risk of arrhythmic death and cardiac arrest in
patients with: CAD, EF  0.40, and asymptomatic NSVT
• Primary endpoint: arrhythmic death or cardiac arrest.
• Secondary endpoint: Total mortality, cardiac mortality,
sustained VT.
Multicenter Unsustained Tachycardia (MUSTT)
Trial
CAD, NSVT, EF
0.40
Evaluate and Treat Ischemia
EPS
N=2202
No Sustained VT Induced
N=1435 (65%)
Registry
N Engl J Med 1996; 1747S-51S
Inducible Sustained VT
N=767 (35%)
Randomized
N=704 (92%)
Refused
Randomization
N=63 (8%)
MUSTT Results
N Engl J Med 1996; 1747S-51S
MUSTT Conclusion
For CAD patients with EF < .40, asymptomatic NSVT and
inducible VT:
• ICD therapy significantly reduces the incidence of:
– Arrhythmic death or cardiac arrest (73% – 76%
reduction)
– Total mortality (55% – 60% reduction)
• EP-guided pharmacologic antiarrhythmic therapy provides
no survival benefit
MULTICENTER AUTOMATIC DEFIBRILLATOR
IMPLANTATION TRIAL-II (MADIT-II)
1997-2001
A trial designed to evaluate the effect of prophylactic
ICD therapy on survival in patients with prior MI and
LV dysfunction.
Supported by a research grant from Guidant Corp.
MADIT-II: Eligibility
•
•
•
•
Chronic CAD with prior MI
EF<0.30
No requirement for NSVT or EPS
No upper age limitation
Multicenter Automatic Defibrillator Implantation Trial II
(MADIT II)
•
•
•
•
1232 patients ≥ 1 month post-MI and LVEF ≤ 30%
Randomized to ICD (n=742) or medical therapy (n=490)
No spontaneous or induced arrhythmia required for enrollment
6% absolute and 31% relative risk ↓ in all-cause mortality with
ICD therapy (p=0.016)
Moss AJ, Zareba W, Hall WJ, et al. Prophylactic
MADIT-II: CONCLUSION
• In coronary patients with LVEF
<0.30, prophylactic ICD therapy is
associated with 31% reduction in
mortality.
• This improved survival is on top of
optimal medical Rx.
SCD-HeFT
(Sudden Cardiac Death in Heart Failure Trial)
DCM + CAD and CHF
EF < 35%
NYHA Class II or III
6-Minute Walk, Holter
R
Placebo N = 847
Amiodarone N = 845
2521 Patients
ICD Implant N = 829
Minimum of 2.5 years follow-up required
45 months average follow-up
Optimized B, ACE-I, Diuretics
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Endpoints
Primary:
• Overall Mortality
Secondary:
• Mortality: ischemic vs. non-ischemic
• Mortality: NYHA Class II vs. III
• Mortality by Sub Groups: age, gender,
LVEF, MI Hx, time of MI, QRS width
• Cause-Specific Death
• HF Morbidity and Mortality
• Quality of Life
• Cost of Care and Cost-Effectiveness
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Mortality Rate Overall Results
Amiodarone vs. Placebo
ICD vs. Placebo
0.4
Hazard Ratio (97.5% Cl)
1.06 (0.86 - 1.30)
0.77 (0.62 - 0.96)
Mortality Rate
0.3
0.2
0.1
Amiodarone
Placebo
ICD
0.0
0
No. at Risk
Amiodarone
Placebo
ICD
12
24
36
48
60
280
304
304
97
89
103
Months of Follow-Up
845
847
829
Bardy GH. N Engl J Med. 2005;352:225-237.
772
797
778
715
724
733
484
505
501
P-Value
0.53
0.007
Sudden Death in Heart Failure
(SCD-HeFT) Trial
• 2521 patients with NYHA Class II or III HF, ICM, or
NICM and LVEF ≤ 35%
• Randomized to
1) conventional rx for HF + placebo;
2) conventional rx + amiodarone; or
3) conventional rx + conservatively programmed shockonly single lead ICD
• No survival benefit for amiodarone
• 23% ↓ in overall mortality with ICD therapy
• Absolute ↓ in mortality of 7.2% after 5 y in the overall
population
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an
COMPANION
Comparison of Medical Therapy, Pacing and
Defibrillation in Heart Failure Trial
Bristow M. N Engl J Med. 2004;350:2140-2150.
COMPANION
Objective:
• Evaluate the effectiveness of CRT with or without
an ICD in reducing the risk of death and hospitalizations
in patients with advanced heart failure and intraventricular
conduction delays
Primary Endpoint:
• Composite of death from any cause or hospitalization
for any cause
Secondary Endpoint:
• Death from any cause
Bristow M. N Engl J Med. 2004;350:2140-2150.
COMPANION Inclusion Criteria
• NYHA Class III or IV (ischemic or
non-ischemic)
• LVEF ≤ 35%, LVEDD ≥ 60 mm
• QRS ≥ 120 ms, PR interval > 150 ms
• Hx of HF hospitalization < 12 months,
> 1 month prior to enrollment
Bristow M. N Engl J Med. 2004;350:2140-2150.
COMPANION Study Design
•
•
•
Prospective randomized study
1520 patients randomized 1:2:2 to three arms:
– 308 Optimal Pharmacological Therapy (OPT) alone
– 617 OPT + CRT
– 595 OPT + CRT-D
Median follow-up: 11.9 - 16.2 months
Bristow M. N Engl J Med. 2004;350:2140-2150.
COMPANION All-Cause Death Results
Event-Free Survival (%)
100
OPT
CRT
CRT-D
90
(CRT vs. OPT) P = 0.059
(CRT-D vs. OPT) P = 0.003
80
70
60
50
0
90
180
270
360 450 540
630
720
810 900 990 1080
Days from Randomization
No. at Risk
OPT
CRT
CRT-D
308
617
595
284
579
555
255
520
517
217
488
470
Bristow M. N Engl J Med. 2004;350:2140-2150.
186
439
420
141
355
331
94
251
219
57
164
148
45
104
95
25
60
47
4
25
21
2
5
1
COMPANION Conclusions
• In patients with advanced heart failure and prolonged QRS:
– CRT and CRT-D reduce all-cause death
and all cause hospitalizations by 19-20%
– CRT reduces all-cause mortality by 24%
– CRT-D reduces all-cause mortality by 36%
Bristow M. N Engl J Med. 2004;350:2140-2150.
Comparison of Medical Therapy, Pacing, and Defibrillation
in Heart Failure (COMPANION) Trial
• 1520 patients with NYHA Class III or IV HF, ischemic
cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM)
and QRS ≥ 120 ms
• Randomized 1:2:2 to optimal pharmacological therapy (OPT)
alone or in combination with cardiac resynchronization therapy
with either a pacemaker (CRT-P) or pacemaker-defibrillator
(CRT-D)
• Both device arms significantly ↓ combined risk of all-cause
hospitalization and all-cause mortality by ~20% compared with
OPT
• CRT-D ↓ mortality by 36% compared with OPT (p=0.003)
• Insufficient evidence to conclude that CRT-P inferior to CRT-D
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-
Defibrillator in Acute Myocardial Infarction
(DINAMIT) Trial
• 674 patients 6 to 40 days post-MI with LVEF ≤ 35% and
impaired cardiac autonomic function
• Randomized to ICD therapy (n=332) or no ICD therapy
(n=342)
• Arrhythmic death ↓ in ICD group, but ↑ in nonarrhythmic
death (6.1% per year vs. 3.5% per year, HR 1.75 (95% CI
1.11 to 2.76; p=0.016)
• No difference in total mortality
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use
Defibrillators in Nonischemic Cardiomyopathy Treatment
Evaluation (DEFINITE) Trial
• 458 patients with NYHA Class I to III, NICM, LVEF ≤
35% and premature ventricular contractions (> 10/h) or
NSVT
• Randomized to standard medical rx alone or in
combination with single-chamber ICD
• Strong trend toward ↓ all-cause mortality with ICD
therapy, although not statistically significant (p=0.08)
Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator
ICD Trials Summary
60%
54%
70%
60%
50%
40%
31%
30%
31%
20% NS
20%
10%
0%
AVID1
3 years
1
CIDS2
3 years
MADIT3
2 years
The AVID Investigators. N Engl J Med. 1997;337:15761583.
2 Connolly SJ. Circulation. 2000; 101; 1297-1302.
3 Moss AJ. N Engl J Med. 1996;335;1933-1940.
MUSTT4
2 years
MADIT II5
2 years
4
Buxton AE. N Engl J Med. 1999; 341:1882-90.
5
Moss AJ. N Engl J Med. 2002;346:877-83.
Atrial ICD shock for AF
Recent implantable cardiac
resynchronization (CRT) devices
allow electrical therapies to treat AF
automatically. TRADE-HF (trial
registration: NCT00345592;
http://www.clinicaltrials.gov webcite
CRT pacemaker with the additional ability to
convert AF as well as ventricular arrhythmias may
play a simultaneous role in rhythm control and HF
treatment. The value of the systematic
implantation of CRT ICDs with the capacity to
deliver atrial therapy in HF patients at risk of AF
has not yet been explored.
Predictors of implantable cardioverterdefibrillator use in patients with ischemic
cardiomyopathy.
“Reduced left ventricular ejection
fraction (LVEF) remains
the single most important risk factor
for overall mortality
and sudden cardiac death.”1
EF and ventricular events
Impact of left ventricular ejection fraction on
occurrence of ventricular events in
defibrillator patients with coronary artery
disease.
Schaer B, Sticherling C, Szili-Torok T, Osswald S,
Jordaens L, Theuns DA.
More ICD-therapies occurred in patients with
poorer LVEF, but the difference was significant
only with the cut-off value of ≤/>20%. Only 2 of
12 parameters were predictors of appropriate ICD
therapy
Prediction of life-threatening arrhythmias-still an unresolved problem.
Haugaa KH, Edvardsen T, Amlie JP.
Left ventricular ejection fraction (EF) is currently the main risk
stratification tool used to select patients for ICD therapy.
However, EF is insufficient in predicting arrhythmic risk. A
number of techniques have been presented to improve
arrhythmic risk stratification without having reached clinical
utility. Conduction abnormalities and dispersion of action
potential duration forms the substrate for malignant ventricular
arrhythmias in infarcted tissue as in several cardiomyopathies.
The ability to assess electrical dispersion in patients
noninvasively has been limited. Myocardial strain by
echocardiography has been presented as an accurate tool for
assessing myocardial function and timing. Inhomogeneous
and dispersed myocardial contraction has been related to the
occurrence of ventricular arrhythmias and seems to be a
promising tool in risk stratification. This review focuses on
arrhythmia mechanisms and novel echocardiographic tools for
assessing risk of ventricular arrhythmias.
Predicting Ventricular Arrhythmias in Patients With
Ischemic Heart Disease
Clinical Application of the ECG-Derived QRS-T Angle
C. Jan Willem Borleffs, MD,
Roderick W.C. Scherptong, MD,
Sum-Che Man, MD,
Guido H. van Welsenes, MS,
Jeroen J. Bax, MD, PhD,
Lieselot van Erven, MD, PhD,
Cees A. Swenne, PhD and
Martin J. Schalij, MD, PhD
A wide QRS-T angle is a strong predictor of appropriate
device therapy in primary prevention ICD recipients with
ischemic heart disease. Furthermore, a spatial QRS-T angle
≤100° might be of value in the identification of patients in
whom, although currently indicated, ICD treatment should be
reconsidered.
Findings suggest that CABG patients with ischemic
cardiomyopathy have low rates of ICD utilization. This is
particularly evident among females and elderly patients.
Furthermore our data suggests that few patients postrevascularization undergo follow-up EF assessment despite
current guidelines likely contributing to the low rates of ICD
utilization
Effect of implantable cardioverterdefibrillator on left ventricular ejection
fraction in patients with idiopathic dilated
cardiomyopathy.
In patients with idiopathic dilated cardiomyopathy,
the potential for LVEF improvement is considerable
and that the rate of ICD interventions strongly
depends on the prevention mode and LVEF. These
findings could be the basis for additional risk
stratification tools.
The results of meta-analysis provide strong evidence for the
beneficial effect of ICD-only therapy on the survival of
patients with ischaemic or non-ischaemic heart disease, with a
left ventricular ejection fraction ≤ 35%, if they are 40 days
from myocardial infarction and ≥ 3 months from a coronary
revascularization procedure.
Indications for ICD Therapy
Implantable Cardioverter-Defibrillators
I IIaIIb
IIbIII
III
ICD therapy is indicated in patients who are survivors of
cardiac arrest due to ventricular fibrillation or hemodynamically
unstable sustained VT after evaluation to define the cause of the
event and to exclude any completely reversible causes.
I IIaIIbIII
ICD therapy is indicated in patients with structural heart disease
and spontaneous sustained VT, whether hemodynamically
stable or unstable.
I IIaIIbIII
ICD therapy is indicated in patients with syncope of
undetermined origin with clinically relevant, hemodynamically
significant sustained VT or VF induced at electrophysiological
study.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
capacity for more than 1 year.
Implantable Cardioverter-Defibrillators
I IIaIIb
IIbIII
III
ICD therapy is indicated in patients with LVEF less than or
equal to 35% due to prior MI who are at least 40 days post-MI
and are in NYHA functional Class II or III.
I IIaIIbIII
ICD therapy is indicated in patients with nonischemic DCM who
have an LVEF less than or equal to 35% and who are in NYHA
functional Class II or III.
I IIaIIb
IIbIII
III
ICD therapy is indicated in patients with LV dysfunction due to
prior MI who are at least 40 days post-MI, have an LVEF less
than or equal to 30%, and are in NYHA functional Class I.
I IIaIIbIII
ICD therapy is indicated in patients with nonsustained VT due to
prior MI, LVEF less than or equal to 40%, and inducible VF or
sustained VT at electrophysiological study.
All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal
medical therapy and have reasonable expectation of survival with good functional capacity for more
than 1 year.
Implantable Cardioverter-Defibrillators
I IIaIIbIII
ICD implantation is reasonable for patients with unexplained syncope,
significant LV dysfunction, and nonischemic DCM.
I IIaIIbIII ICD implantation is reasonable for patients with sustained VT and normal
or near-normal ventricular function.
I IIaIIbIII ICD implantation is reasonable for patients with HCM who have 1 or
more major† risk factors for SCD.
ICD implantation is reasonable for the prevention of SCD in patients with
I IIaIIbIII arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
who have 1 or more risk factors for SCD.
ICD implantation is reasonable to reduce SCD in patients with long-QT
I IIaIIbIII syndrome who are experiencing syncope and/or VT while receiving beta
blockers.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
capacity for more than 1 year.
Implantable Cardioverter-Defibrillators
I IIaIIbIII
ICD implantation is reasonable for nonhospitalized patients
awaiting transplantation.
I IIaIIbIII
ICD implantation is reasonable for patients with Brugada
syndrome who have had syncope.
I IIaIIbIII
ICD implantation is reasonable for patients with Brugada
syndrome who have documented VT that has not resulted in
cardiac arrest.
I IIaIIbIII
ICD implantation is reasonable for patients with
catecholaminergic polymorphic VT who have syncope and/or
documented sustained VT while receiving beta blockers.
I IIaIIbIII
ICD implantation is reasonable for patients with cardiac
sarcoidosis, giant cell myocarditis, or Chagas disease.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
Implantable Cardioverter-Defibrillators
I IIaIIbIII
ICD therapy may be considered in patients with nonischemic heart
disease who have an LVEF of less than or equal to 35% and who
are in NYHA functional Class I.
I IIaIIb
IIbIII
III ICD therapy may be considered for patients with long-QT
syndrome and risk factors for SCD.
I IIaIIbIII
ICD therapy may be considered in patients with syncope and
advanced structural heart disease in whom thorough invasive and
noninvasive investigations have failed to define a cause.
I IIaIIbIII
ICD therapy may be considered in patients with a familial
cardiomyopathy associated with sudden death.
I IIaIIbIII
ICD therapy may be considered in patients with LV
noncompaction.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
Implantable Cardioverter-Defibrillators
I IIaIIbIII
I IIaIIbIII
ICD therapy is not indicated for patients who do not have a
reasonable expectation of survival with an acceptable
functional status for at least 1 year, even if they meet ICD
implantation criteria specified in the Class I, IIa, and IIb
recommendations above.
ICD therapy is not indicated for patients with incessant VT or
VF.
I IIaIIbIII
ICD therapy is not indicated in patients with significant
psychiatric illnesses that may be aggravated by device
implantation or that may preclude systematic follow-up.
I IIaIIbIII
ICD therapy is not indicated for NYHA Class IV patients with
drug-refractory congestive heart failure who are not candidates
for cardiac transplantation or cardiac resynchronization therapy
defibrillators (CRT-D).
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
Implantable Cardioverter-Defibrillators
I IIaIIbIII
I IIaIIbIII
I IIaIIbIII
ICD therapy is not indicated for syncope of undetermined cause
in a patient without inducible ventricular tachyarrhythmias and
without structural heart disease.
ICD therapy is not indicated when VF or VT is amenable to
surgical or catheter ablation (e.g., atrial arrhythmias associated
with the Wolff-Parkinson-White syndrome, RV or LV outflow
tract VT, idiopathic VT, or fascicular VT in the absence of
structural heart disease).
ICD therapy is not indicated for patients with ventricular
tachyarrhythmias due to a completely reversible disorder in the
absence of structural heart disease (e.g., electrolyte imbalance,
drugs, or trauma).
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
capacity for more than 1 year.
ICDs in Pediatric Patients and Patients With
Congenital Heart Disease
I IIaIIbIII
I IIaIIbIII
ICD implantation is indicated in the survivor of cardiac
arrest after evaluation to define the cause of the event
and exclusion of any reversible causes.
ICD implantation is indicated for patients with
symptomatic sustained VT in association with congenital
heart disease who have undergone hemodynamic and
electrophysiological evaluation. Catheter ablation or
surgical repair may offer possible alternatives in
carefully selected patients.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
capacity for more than 1 year.
ICDs in Pediatric Patients and Patients With
Congenital Heart Disease
I IIaIIb
IIbIII
III
ICD implantation is reasonable for patients with congenital heart
disease with recurrent syncope of undetermined origin in the
presence of either ventricular dysfunction or inducible ventricular
arrhythmias at electrophysiological study.
I IIaIIbIII
ICD implantation may be considered for patients with recurrent
syncope associated with complex congenital heart disease and
advanced systemic ventricular dysfunction when thorough invasive
and noninvasive investigations have failed to define a cause.
I IIaIIbIII
All Class III recommendations found in Section 3 of the full-text
guidelines, “Indications for Implantable Cardioverter-Defibrillator
Therapy,” apply to pediatric patients and patients with congenital
heart disease, and ICD implantation is not indicated in these patient
populations.
All primary SCD prevention ICD recommendations apply only to patients who are receiving
optimal medical therapy and have reasonable expectation of survival with good functional
capacity for more than 1 year.
Summary
• Primary Prevention:
– ICMP:
• EF ≤ 35% at least 1 month post MI or 3 months post
revascularization.
• EF ≤ 40% with NSVT and inducible VT.
– NICMP:
• EF ≤ 35% for at least 3 months.
• Must have NYHA class II or III.
Summary
• Secondary Prevention:
– SCD due to VF or VT (not reversible cause)
– Sustained VT/VF with structural heart disease
– Recurrent syncope with inducible VT/VF.
• Special situations:
– Recurrent unexplained syncope (for EPS)
– Familial disease with symptoms.
Take home message
• The vast majority of cases of SCD are due to
ventricular arrhythmias
• The causes of SCD is different in different age
groups
• The most effective strategy for prevention of SCD
is implantable cardioverter defibrillator (ICD)
• Strictly speaking, most victims of SCD can not be
the donor of heart transplantation
Cardiac Resynchronization
Sinus
node
AV
node
Conduction
block
• Delayed lateral wall
contraction
• Disorganized ventricular
contraction
• Decreased pumping
efficiency
Abnormal wall motion
Healthy
Courtesy of C. Stellbrink, MD.
Dysynchrony
Ventricular resynchronization
Sinus
node
• Intraventricular Activation
• Organized ventricular
activation sequence
• Coordinated septal and
free-wall contraction
• Improved pumping
efficiency
AV
node
Conduction
block
Stimulation
therapy
Cardiac resynchronization therapy (CRT)
Baseline
Courtesy of C. Stellbrink, MD.
DCM with CRT
ACC/AHA Classification of Recommendations
• Class I:
– Conditions for which there is evidence and/or general agreement that a
given procedure or treatment is beneficial, useful, and effective
• Class II:
– Conditions for which there is conflicting evidence and/or a divergence
of opinion about the usefulness/efficacy of a procedure or treatment
– Class IIa:
Weight of evidence/opinion is in favor of
usefulness/efficacy
– Class IIb:
Usefulness/efficacy is less well established by
evidence/opinion
• Class III:
– Conditions for which there is evidence and/or general agreement that a
procedure/treatment is not useful/effective and in some cases may be
harmful
Class I
• Cardiac arrest due to VF or VT not due to a transient or
reversible cause.
• Spontaneous sustained VT in association with structural heart
disease.
• Spontaneous sustained VT in patients without structural heart
disease not amenable to other treatments
• Syncope of undetermined origin with clinically relevant,
hemodynamically significant sustained VT or VF induced at
electrophysiologic study when drug therapy is ineffective, not
tolerated, or not preferred.
Implantable Cardioverter-Defibrillators
I IIa IIb
IIbIII
III
I IIa IIb
IIbIII
III
I IIa IIb III
I IIa IIb III
ICD therapy is indicated in patients with LVEF less than 35%
due to prior MI who are at least 40 days post-MI and are in
NYHA functional Class II or III.
ICD therapy is indicated in patients with LV dysfunction due
to prior MI who are at least 40 days post-MI, have an LVEF
less than or equal to 30%, and are in NYHA functional Class I.
ICD therapy is indicated in patients with nonischemic DCM
who have an LVEF less than or equal to 35% and who are in
NYHA functional Class II or III.
ICD therapy is indicated in patients with nonsustained VT due
to prior MI, LVEF less than 40%, and inducible VF or
sustained VT at electrophysiological study.
All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical therapy and have reasonable expectation of
survival with good functional capacity for more than 1 year.
CRT Guideline
• LVEF less than or equal to 35%,
• NYHA functional class III or ambulatory class IV symptoms
despite recommended, optimal medical therapy
• cardiac dyssynchrony: QRS duration greater than 120 ms,
1.
2.
3.
Supporting Clinical Trials
MIRACLE: Abraham WT. N Engl J Med 2002;346:1845-1853.
COMPANION: 2 Bristow M. N Engl J Med 2004;350:1140-1150.
CARE-HF: Cleland JGF. N Engl J Med 2005;352:1539-1549.
MADIT-CRT
• Ischemic heart disease (NYHA Class I or II) or non-ischemic
heart disease (NYHA Class II) for at least three months prior
to entry
• Optimal pharmacologic therapy
• Left ventricular ejection fraction ≤ 30%
• QRS duration ≥ 130 ms, sinus rhythm
• Primary endpoint:
• of all-cause mortality or heart failure events.
• Secondary endpoint:
• Risk of recurrent heart failure events
Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.
MADIT-CRT: Methods
• Enrollment
– 1820 patients, 110 centers,
14 countries
• Average follow-up
– 34.3 months
Baseline Evaluation
To document inclusion/exclusion criteria and establish baseline
heart status
Randomization (3:2 CRT-D:ICD)
Stratified by center and ischemic status
CRT-D + OPT
(1089 patients)
ICD + OPT
(731 patients)
Clinic Follow-up Visits
1 month post-enrollment/randomization, 3 months postrandomization, and quarterly thereafter to a common study
closure date
aBaseline
evaluation includes history and physical exam, electrocardiogram, and echocardiogram. Patients are randomized and then baseline testing is
completed including BNP (US only), quality-of-life assessment, 6-minute walk test, and Holter monitor recording (CRT-D patients only).
bThe 12-month follow-up visit includes echocardiogram, BNP (US only), 6-minute walk test, Holter monitor recording (CRT-D patients only), and
device interrogation. Other follow-up visits include history and physical exam, clinical events, and device interrogation. Quality-of-life assessments
were conducted at 6-month intervals.
Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.
89
Previously Published and Updated Results
57%
34%
•
Results showed that CRT-D was
associated with a 34% reduction in the
relative risk of the primary endpoint
Moss AJ, et al. N Engl J Med. 2009;361:1329-1338.
•
Additional 6 months of data analyzed
•
It was subsequently discovered and validated
that in the LBBB subgroup, patients received
substantial benefit from CRT-D. Non-LBBB
patients did not show evidence of benefit. The
LBBB sub-group made up approximately 70%
of the total MADIT-CRT population.