Upload
others
View
4
Download
0
Embed Size (px)
Citation preview
©2017 MFMER | 3686275-1
ICD for NICM All in the Past?
Win K. Shen, MD
Mayo Clinic Arizona
Controversies and Advances in CV Diseases
Cedars-Sinai Heart Institute, 2017
©2017 MFMER | 3686275-2
DISCLOSURE
Relevant Financial Relationship(s)
None
Off Label Usage
None
©2017 MFMER | 3686275-3
ICD for Non-Ischemic Cardiomyopathy
• Case discussion
• A patient with narrow QRS: ICD or no ICD, and when?
• A patient with LBBB: CRT-D or CRT-P?
• Why the question?
• Evidence-based discussion
• Guidelines, emergent data and take home message
Objectives
©2017 MFMER | 3686275-4
©2011 MFMER | 3134946-4
62 Year-Old Woman
A 62 year-old woman was admitted to the hospital for evaluation of
SOB, PND and orthopnea. She was found to be in heart failure. EKG
showed SR 90 bpm, QRSD 104 ms. Echo showed an EF of 26%.
Angiogram showed no significant CAD. Work up for cardiomyopathy
was unrevealing.
• She responded to diuretics. Her discharge medications included
metoprolol, valsartan, lasix and K supplement
• She had no signs of heart failure at 3-month follow up. Her
functional class was NYHA II. A repeat echo showed the EF was
32%
©2017 MFMER | 3686275-5
Would you recommend ICD?
1. Yes
2. No
©2017 MFMER | 3686275-6
©2011 MFMER | 3134946-6
* Guidelines: GDMT, exclude reversible transient causes of LV dysfunction (no change in VT guideline 2017)
* Optimal GDMT ≥ 3-9 months: a CMS rule
Primary SCD in Non-ischemic, LVEF ≤ 35%
NYHA
Disease
I II, III IV
Nonischemic* IIB I X
Indications for ICD (guidelines 2012)
©2017 MFMER | 3686275-7
DANISH Trial: NICM, EF ≤ 35%, NYHA II, III, IVa 1,116 patients eligible for randomization
Køber L et al. NEJM 2016; 375:1221-30.
19 had preexisting CRT 626 had indication for CRT 471 did not have indication for CRT
645 underwent randomization 471 underwent randomization
323 assigned to
control group
322 assigned to
ICD group
237 assigned to
control group
234 assigned to
ICD group
• 6 did not undergo
ICD implantation
• 1 Had
unsuccessful
implantation
• 5 withdrew consent
• 19 had ICD extracted
or deactivated
• 8 did not undergo
ICD implantation
• 1 died before
implantation
• 1 had unsuccessful
implantation
• 6 withdrew consent
• 11 had ICD extracted
or deactivated • 306 remained without ICD
during trial
• 17 underwent
ICD implantation
during trial
• 15 had arrhythmia
• 2 underwent implantation at
physician request
303 had ICD
throughout trial
• 227 remained without ICD
during trial
• 10 underwent ICD
implantation during trial
• 9 had arrhythmia
• 1 underwent implantation at
physician request
209 had ICD
throughout trial
©2017 MFMER | 3686275-8
DANISH Trial: Time-to-Event
Køber L et al. NEJM 2016; 375:1221-30.
Cu
mu
lati
ve
E
ven
t R
ate
Hazard ratio, 0.87 (95% CI 0.68–1.12)
P=0.28
0 1 2 3 4 5 6 7 8
Cu
mu
lati
ve
E
ven
t R
ate
Hazard ratio, 0.77 (95% CI 0.57–1.05)
P=0.10
Cu
mu
lati
ve
E
ven
t R
ate
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Hazard ratio, 0.50 (95% CI 0.31–0.82)
P=0.005
0 1 2 3 4 5 6 7 8
0 1 2 3 4 5 6 7 8
Sudden Cardiac Death
Cardiovascular Death Death from Any Cause
Years Years
Years
Control group
ICD group
Control group
ICD group
Control group
ICD group
~ 4-5%/yr ~ 2-3 %/yr
~ 1 – 1.6 %/yr
©2017 MFMER | 3686275-9
CMS Announcement: May 30, 2017
• Reopening national coverage analysis to reconsider indications for ICDs!!
©2017 MFMER | 3686275-10
Non-ischemic CM DEFINITE, EF < 36%, NYHA I-III, NSVT or PVCs (47% had < 90 days from dx to randomization; excluded reversible causes)
0.6
0.7
0.8
0.9
1.0
0 1 2 3 4 5 6
Pro
bab
ilit
y o
f
su
rviv
al
Survival (yr)
ICD group
Standard therapy
Kadish et al, NEJM 2004
At risk (no.)
229 218 140 77 41
229 210 131 67 32
P=0.08
©2017 MFMER | 3686275-11
SCD-HeFT: ICD vs. Amio vs. Medical RX EF ≤ 35%, NYHA II-III, NICM 48%
0.0
0.1
0.2
0.3
0.4
0.5
0 12 24 36 48 60
Mo
rtality
rate
Months of follow-up
Amiodarone (240 deaths;
5-yr event rate 0.340)
Placebo (244 deaths;
5-yr event rate 0.36)
Bardy et al, NEJM 2005
At risk (no.)
845 772 715 484 280 97
847 797 724 505 304 89
829 778 733 501 304 103
HR (97.5% CI) P Amiodarone vs placebo 1.06 (0.86-1.30) 0.53 ICD therapy vs placebo 0.77 (0.62-0.96) 0.007
ICD therapy (182 deaths;
5-yr event rate 0.289)
©2017 MFMER | 3686275-12
NICM Primary SCD Prevention by ICD: Meta-Analysis Total Mortality
Al-Khatib: JAMA Cardiol 2(6): 685, 2017
No. of events No. of events
Source (Trial name)
Duration of follow-up (mo)
ICD group
Control group
ICD group
Control group HR (95% CI) HR (95% CI) Weight (%)
Bänsch et al, 2002 (CAT)
66.0 13 17 50 54 0.81
(0.38-1.71) 7.9
Køber et al, 2016 (DANISH)
67.6 58 65 234 237 0.83
(0.58-1.19) 34.0
Kadish et al, 2004 (DEFINITE)
29.0 28 40 229 229 0.65
(0.40-1.06) 18.6
Bardy et al, 2005 (SCD-HeFT)
45.5 71 95 424 417 0.73
(0.52-1.02) 39.6
Total 170 217 937 937
Fixed effect model 0.75
(0.61-0.93)
Random-effects model 0.75
(0.61-0.93)
Overall P=0.008
Heterogeneity, I2=0%; 2=0; P=0.87
0.50 1.00 2.00
©2017 MFMER | 3686275-13
64 year-old woman has idiopathic DM for 4 years. Despite medical therapy, she now has progressive exertional dyspnea walking 2-3 blocks. Most recent EF was 27%, LVEDD/ESD: 62/52. She has been treated with carvedilol, valsartan, lasix, niacin. She is referred to you for consideration of CRT. EKG is shown, QRSD 144 msec. (Ht 5’1”, Wt 96 Kg)
64 Year-Old Woman
©2017 MFMER | 3686275-14
What Would You Recommend?
1. CRT-P
2. CRT-D
©2017 MFMER | 3686275-15
CRT Indications
Class LVEF NYHA class IVCD pattern QRS (ms) Rhythm Disease
IA (B) ≤35% II, III, IVa LBBB ≥150 Sinus Any
IIA ≤35% II, III, IVa LBBB 120-149 Sinus Any
IIA ≤35% III, IVa Non LBBB ≥150 Sinus Any
IIA ≤35% II, III, IVa V pacing or QRS criteria+ rate
control AF Any
IIA ≤35% II, III, IVa V pacing >40% NA Sinus Any
IIB ≤30% I LBBB ≥150 Sinus Ischemia
IIB ≤35% III, IVa Non LBBB 120-149 Sinus Any
IIB ≤35% II Non LBBB ≥150 Sinus Any
2012 ACCF/AHA/HRS Focused Update; 2013 ACCF/AHA HF Guidelines
©2017 MFMER | 3686275-16
Outcomes of CRT Trials
• Improvement in 6 minute walk test, 20%
• Improvement of O2 consumption, 10 – 15%
• Improvement in NYHA functional class - most trials approx 0.5 – 0.8 points, EF ~ 0.04 – 0.06
• Average decrease in Mn Living with Heart Failure Score of approx 10 points
• Fairly consistent on secondary endpoint of decreased hospitalization for CHF, 35 – 50%
• All cause mortality
• COMPANION: CRT-D, 36% relative reduction (p 0.003)
CRT-P, 24% relative reduction (p 0.059)
• CARE-HF: CRT-P 36% relative reduction (p < 0.002)
Improvement in 70% of patients
©2017 MFMER | 3686275-17
COMPANION (NYHA III, IVa, NICM 44%) Death from Any Cause
50
60
70
80
90
100
0 90 180 270 360 450 540 630 720 810 900 990 1,080
Days after randomization
Event-free survival
(%)
Bristow et al: NEJM, 2004
No. at risk
Pharmacologic 308 284 255 217 186 141 94 57 45 25 4 2
therapy
CRT-P 617 579 520 488 439 355 251 164 104 60 25 5
CRT-D 595 555 517 470 420 331 219 148 95 47 21 1
Pharmacologi
c therapy
(77 events) CRT-P
(131 events, P=0.059)
CRT-D
(105 events, P=0.003)
©2017 MFMER | 3686275-18
CRT-D vs CRT-P: All-Cause Mortality
Sérgio et al: J Am Heart Assoc. 2015;4:e002539 doi: 10.1161
Study or subgroup Log hazard ratio) SE Weight
Hazard ratio
IV, random, 95% CI
Hazard ratio
IV, random, 95% CI
Morani 2013 -0.215 0.244 12.5% 0.81 (0.50, 1.30)
Kutyifa 2014 -0.357 0.166 27.1% 0.70 (0.51, 0.97)
Looi 2014 -0.411 0.258 11.2% 0.66 (0.40, 1.10)
Reitan 2015 -0.734 0.273 10.0% 0.48 (0.28, 0.82)
Witt -0.301 0.138 39.2% 0.74 (0.56, 0.97)
Total (95% CI) 100.0% 0.70 (0.59, 0.83)
Heterogeneity: Tau2=0.00; Chi2=2.45, df=4 (P=0.65); I2=0%
Test for overall effect: Z=4.18 (P<0.00001)
0.5 0.7 1 1.5 2
Favors CRT-D Favors CRT-P
Study or subgroup Log hazard ratio) SE Weight
Hazard ratio
IV, random, 95% CI
Hazard ratio
IV, random, 95% CI
Morani 2013 -0.579 0.209 23.8% 0.56 (0.37, 0.84)
Kutyifa 2014 -0.02 0.152 32.9% 0.98 (0.73, 1.32)
Looi 2014 -0.231 0.299 14.7% 0.79 (0.44, 1.43)
Reitan 2015 -0.654 0.447 7.6% 0.52 (0.22, 1.25)
Witt -0.041 0.231 21.0% 0.96 (0.61, 1.51)
Total (95% CI) 100.0% 0.79 (0.61, 1.02)
Heterogeneity: Tau2=0.00; Chi2=6.20, df=4 (P=0.18); I2=36%
Test for overall effect: Z=1.78 (P=0.07)
0.5 0.7 1 1.5 2
Favors CRT-D Favors CRT-P
Non-ischemic cardiomyopathy
Ischemic cardiomyopathy
©2017 MFMER | 3686275-19
Study HR (95% CI) Weight (%)
ICD/CRT-D vs. GDMT
CAT 0.83 (0.45, 1.52) 7.92
AMIOVIRT 0.87 (0.31, 2.42) 2.78
DEFINITE 0.65 (0.40, 1.060 12.36
SCD-HeFT 0.73 (0.50, 1.07) 20.28
COMPANION 0.50 (0.29, 0.88) 9.53
DANISH 0.87 (0.68, 1.12) 47.14
Subtotal (I2=0.0%; P=0.565) 0.77 (0.64, 0.91) 100.00
CRT-D vs. CRT-P
COMPANION 0.50 (0.29, 0.88) 43.28
DANISH (CRT) 0.91 (0.64, 1.29) 56.72
Subtotal (I2=68.7%; P=0.074) 0.70 (0.39, 1.26) 100.00
ICD vs. GDMT
CAT 0.83 (0.45, 1.52) 11.99
AMIOVIRT 0.87 (0.31, 2.42) 4.21
DEFINITE 0.65 (0.40, 1.06) 18.71
SCD-HeFT 0.73 (0.50, 1.07) 30.70
DANISH (No CRT) 0.83 (0.58, 1.19) 34.40
Subtotal (I2=0.0%; P=0.937) 0.76 (0.62, 0.94) 100.00
All-Cause Mortality: NICM ICD and CRT-D vs Medical Therapy for Primary SCD Prevention
0.2 0.6 1 1.8 5 Favors device Favors no device
Note: weights are from random effects analysis Golwala et al: Circ 135(2): 201, 2017
©2017 MFMER | 3686275-20
DANISH Trial: Subgroup Analysis, All-Cause Mortality
Køber, et al: N Engl J Med; 375:1221, 2016
Hazard Ratio (95% CI) ICD Group Control Group
Age <59 yr 59 to <68 yr 68 yr
Sex Female Male
NT-proBNP <1177 pg/ml 1177 pg/ml
LV ejection fraction <25% 25%
Estimated GFR <73 ml/min/1.73 m2
73 ml/min/1.73 m2
NYHA functional class II III–IV
Heart failure duration <18 mo 18 mo
Hypertension No Yes
Diabetes No Yes
Permanent atrial fibrillation No Yes
Cause of heart failure Idiopathic Valvular Hypertension Other
Preexisting pacemaker No Yes
CRT No Yes
Overall
Subgroup P Value for
Interaction
17/167 36/173 67/216
22/151 98/405
32/266 57/292
70/264 50/292
75/272 45/283
52/297 68/259
31/254 89/301
78/375 42/181
87/457 33/99
83/421 37/135
90/424 4/20
13/62 13/50
108/500 12/56
58/234 62/322
34/181 50/202 47/177
23/156 108/404
74/268 88/290
65/242 66/318
80/278 50/280
54/300 77/260
36/277 95/283
87/392 44/167
95/448 36/112
91/447 40/113
100/425 5/21
12/55 14/59
120/514 11/46
65/237 66/323
0.009
0.66
0.06
0.69
0.86
0.71
0.73
0.63
0.60
0.30
0.80
0.71
0.73
P Value
0.51 (0.29-0.92) 0.75 (0.48-1.16) 1.19 (0.81-1.73)
1.03 (0.57-1.87) 0.85 (0.64-1.12)
0.59 (0.38-0.91) 0.99 (0.73-1.36)
0.87 (0.62-1.22) 0.79 (0.54-1.14)
0.88 (0.64-1.21) 0.82 (0.55-1.23)
0.92 (0.63-1.35) 0.81 (0.58-1.13)
0.88 (0.54-1.43) 0.81 (0.61-1.09)
0.90 (0.66-1.22) 0.79 (0.51-1.21)
0.85 (0.63-1.31) 0.92 (0.57-1.50)
0.92 (0.68-1.24) 0.76 (0.48-1.20)
0.88 (0.66-1.17) 0.59 (0.13-2.71) 0.68 (0.29-1.63) 1.02 (0.47-2.20)
0.88 (0.68-1.14) 0.88 (0.36-2.20)
0.83 (0.58-1.19) 0.91 (0.64-1.29) 0.87 (0.68-1.12)
0.02 0.19 0.38
0.92 0.24
0.02 0.96
0.42 0.21
0.42 0.33
0.68 0.21
0.61 0.17
0.48 0.27
0.26 0.74
0.58 0.24
0.37 0.50 0.39 0.96
0.34 0.79
0.31 0.59 0.28
no. of events/total no.
0.25 0.50 1.00 2.00
ICD Better Control Better
©2017 MFMER | 3686275-21
Trends in the Rate of Sudden Death Across Trial Groups Over Time
1
2
3
4
5
6
7
8
9
10
N Engl J Med 2017;377:41-51
Year of randomization
An
nu
al
rate
of
su
dd
en
death
(per
100 p
ati
en
t-yr)
Control group
Experimental-therapy group
Slope (per decade), -1.22 per 100 patient-yr; P=0.02
CORONA PARADIGM-HF
EMPHASIS-HF GISSI-HF
RALES
MERIT-HF BEST
RALES
BEST CIBIS-II
CIBIS-II
Val-HeFT
MERIT-HF
SCD-HeFT SCD-HeFT
CHARM-Added
CHARM-Alternative
CHARM-Added
CHARM-Alternative
Population 3000
1000
©2017 MFMER | 3686275-22
ICD for NICM: All in the Past?
• Not yet!!
• ICD vs. GDMT: CAT, DEFINITE, SCD-HeFT, DANISH
• Mortality benefit not shown from each trial individually
• Together, mortality was reduced by 23%, significant
• CRT-D vs. CRT-P: COMPANION, DANISH, Non-RCT
• A trend towards mortality reduction in favor of CRT-D
• Patient population is heterogeneous
• CRT-D for younger patients, less comorbidity, NYHA II
Take Home Message
©2017 MFMER | 3686275-23
ICD in NICM All in the Past?
Cedars 2017
©2017 MFMER | 3686275-24
Win K. Shen, MD
Mayo Clinic Arizona
Controversies and Advances in CV Diseases
Cedars-Sinai Heart Institute, 2017
ICD for NICM All in the Past?