Transcript New risk assessment tools

M. Tayyebi, MD
Interventional Electrophysiologist, MUMS
 ICDs:
battery-powered implantable devices,
monitor heart rhythm, deliver therapy: electric
shock or ATP when VA
 who survived sustained VA
 also primary prevention

No previous sustained VA, but RF
 may
include CRT for additional HF treatment
Uhlig K.. Rockville, MD: Agency for Healthcare Research and Quality. June 2013.
 Most
studies excluded older adults >70 -80 y
 SCD: 4-13 % of controls: 2-5 years after Rand.
 Meta-analysis of seven RCTs:


NNT to prevent one death: 6.2 to 22 at the longest
durations of follow-up (3-7y)
Meta-analysis of five studies:

NNT to prevent one Ar. death: 2 to 11
Uhlig K.. Rockville, MD: Agency for Healthcare Research and Quality. June 2013.
 Three
other trials ICDs implanted immediately
after MI or at the time of CABG:


No benefit for all-cause mortality
Two show a reduction in SCD
 Three

RCTs (low strength of evidence)
No consistent effect of ICD placement on QOL
 No
differences for all-cause mortality or SCD
across subgroups: age, sex, and other patient
characteristics
Uhlig K.. Rockville, MD: Agency for Healthcare Research and Quality. June 2013.
 High


early (in-hospital) adverse event rates: 3%
serious adverse event rates: 1 %.
 Low

strength of evidence:
strength of evidence:
variable, late (out of hospital) rates for device- and
lead-related adverse events
 Moderate

strength evidence:
3-21 % at least one inappropriate shock in 1-5 y
follow-up
Uhlig K.. Rockville, MD: Agency for Healthcare Research and Quality. June 2013.
 High

strength of evidence:
ICD therapy for primary prevention of SCD: benefit
with regard to all cause mortality and SCD in Pts
with reduced LVEF and ischemic or nonischemic
cardiomyopathy beyond the immediate post-MI or
coronary revascularization periods
Uhlig K.. Rockville, MD: Agency for Healthcare Research and Quality. June 2013.
 ICD



therapy for primary prevention of SCD:
LVEFs ≤35% due to previous MI ≥ 40 d post-MI and
NYHA class II or III
Non-ischemic DCM, LVEFs ≤35% and NYHA class II
or III
LVEFs ≤30% due to previous MI ≥ 40 d post-MI and
NYHA class I
 primary
prevention: 53.0% of first implantations
1- Epstein AE. Circulation. 2008;117:e350-408.
2- Alzueta J. Rev Esp Cardiol . 2014 Oct 1. pii: S1885-5857(14)00327-2.
 320
Pts primary prevention followed 40 m:
 all–cause mortality 14 % (CAD 15 % vs DCM 13
%).
 Appropriate shocks 13 % (CAD 15 % vs DCM 11
%, p=0.12)
 Inappropriate shocks 10 % (CAD 8 % vs DCM 12
%, p=0.27)
Verhagen MP. Neth Heart J. 2014 Oct;22(10):431-7.
 Subgroups:
sex, age, NYHA, LVEF, HF, LBBB,
QRS interval, time since MI, BUN, DM
 Weak evidence:

No differences all-cause mortality in subgroups of
sex, age, QRS interval
 Indeterminate

evidence
all-cause mortality in other subgroups and for SCD
 Individualize
treatment decisions in clinical
practice: each Pts prognosis
Earley A. Ann Intern Med. 2014 Jan 21;160(2):111-21.
 ICDs
effective reducing all-cause mortality in
moderate to severe systolic dysfunction
regardless of QRS duration
 QRS
duration of at least 120 ms: greater
mortality benefit
Sipahi I. J Cardiovasc Med (Hagerstown). 2014 Jul 10.
 Women
less likely correct ICD treatment
 Same degree of complications
 Less net benefit
Sjöblom J. Europace. 2014 Sep 10. pii: euu219.
 Pts
with extensive comorbid medical illnesses
may less benefit
 Implantation should be carefully considered in
sick Pts
Steinberg BA. JACC Heart Fail. 2014 Sep 27. pii: S2213-1779(14)00331-X.

Factors serve as a substrate or trigger of VT/VF
and/or abnormalities in ventricular conduction and
repolarization critical to reentry
1)
2)
3)
4)
5)
6)

slowed conduction (QRS duration, SAECG)
heterogeneities in ventricular repolarization (QT interval,
QT dispersion, T-wave alternans)
imbalance in autonomic tone (HRV, HR turbulence, HR
recovery after exercise, baroreceptor sensitivity)
extent of myocardial damage and scar formation (LVEF)
ventricular ectopy (long-term ambulatory monitoring)
Electrophysiological testing (inducible VT/VF)
currently no optimal strategy for risk stratification
Goldberger JJ. Circulation 2008;118:1497–518.
The PAREPET study (Prediction of Arrhythmic
Events with Positron Emission Tomography)
 204 Pts, ICM eligible for primary prevention ICD
 Four independent predictors of SCA:

Denervated myocardium > 37.6% of LV: HR=3.5 for SCA
(10.3%/year vs. 3.0%/year, p0.001)
 LVEDV > 98 mL/m2
 Creatinine level>1.49 mg/dL
 No angiotensin-inhibition therapy

Absence of all 4 factors: low risk (SCA 1%/y)
 ≥ 2 factors: high-risk (SCA 12%/y)
 Denervated myocardium using PET strongly predicts
risk of SCA, Independent of EF, infarct volume, and
other clinical variables

Cain ME. Trans Am Clin Climatol Assoc. 2014;125:141-53; discussion 153.
 Prospective
Observational Study of Implantable
Cardioverter-Defibrillators (PROSE-ICD)
 1189 participants, 1,189 participants, median
follow-up 4.0 y, 137 Pts appropriate ICD shock
and 343 death (3.2 and 5.8 per 100 personyears)
 294 out of 343 (85.7%) death: No appropriate ICD
shock
Cheng A. 2014 Oct 1. pii: CIRCEP.113.001705.
 Appropriate

ICD shock
more likely male, Caucasian, current or former
smokers, higher BMI, lower resting HR, less
hypertensive, less likely CKD
 Death:


more often male, current or former smokers, NYHA
Class III, longer QTc intervals and QRS durations,
ICM, AF, DM, HTN, CKD, lower BMI, lower EF, and
lower ICD therapy cutoff rates
more frequently taking diuretics, ASA and ACEI/ARBs compared to survivors
Cheng A. Circ Arrhythm Electrophysiol. 2014 Oct 1. pii: CIRCEP.113.001705.

Higher IL-6 levels increase risk of appropriate ICD shocks (HR
2.23)

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
potentially less useful in identifying patients likely appropriate ICD
shock
In contrast, C-reactive protein, IL-6, tumor necrosis factor-α
receptor II, pro-brain natriuretic peptide, and cardiac troponin T
showed significant linear trends for increased risk of all-cause
mortality
A score combining these 5 biomarkers (5-20) identified Pts who
were much more likely to die than to receive an appropriate
shock from ICD
Increase in serum biomarkers of inflammation, neurohumoral
activation and myocardial injury increased risk for death but
poorly predicted likelihood of ICD shock
These highlight potential importance of serum-based
biomarkers in identifying Pts unlikely to benefit from primary
prevention ICDs
Cheng A. Circ Arrhythm Electrophysiol. 2014 Oct 1. pii: CIRCEP.113.001705.
 Associations
between pro-BNP levels, ICD
shocks and all-cause mortality, similar to the
relationship for markers of inflammation1


Pro-BNP failed to predict ICD shocks
predict death after ICD implantation
 BNP:

additional discriminatory power:
Those at highest risk for death despite primary
prevention ICD implantation
 Some
studies: strong link between BNP levels
and ICD events2-4
 Others do not5,6
1- Cheng A. Circ Arrhythm Electrophysiol. 2014 Oct 1.
2- Scott PA. Eur J Heart Fail.2009;11:958-966.
3- Levine YC. Heart Rhythm. 2014 Jul;11(7):1109-16.
4- Mordi I. JACC Cardiovasc Imaging. 2014 Jun;7(6):561-9.
5- Biasucci LM. Eur Heart J. 2012;33:1344-1350.
6- Battipaglia . Europace.2010;12:1725-1731.
 NT-proBNP
 Meta-analysis

8 studies (1,047 patients)1
NT-proBNP (or BNP) levels above the study median
increased risk of occurrence of death or VA in those
with or without an ICD.
 Another
large study 345 consecutive patients
primary or secondary prevention ICD2

BNP only significant multivariable predictor of death
or appropriate ICD activation
 large
Italian multicenter study, 300 patients ICM,
primary prevention3

NT-proBNP levels above the median: significant
predictor of SCD and VA
1- Scott PA. Eur J Heart Fail 2009;11:958–66.
2-Verma A. Heart 2006;92:190–5.
3- Biasucci LM. Eur Heart J 2012;33:1344–50.
 197
Patients: Prediction of Arrhythmic
Events with Positron Emission
Tomography (PAREPET)
 baseline echocardiogram, PET scan,
and 24 h Holter ECG
 Among Pts with depressed LVEF,
prolonged QTc: greater potential
benefit from ICD therapy for SCA
 Depressed HRV: potential benefit from
BVP to prevent cardiac non-sudden
deaths
Al-Zaiti SS. Heart Lung. 2014 Jul 1. pii: S0147-9563(14)00148-4.
 Lesions
in LAD: 25 (96%) and 28 (74%) Pts in
groups with and without appropriate ICD
therapies
 No significant difference in frequencies of
involvement of other coronary arteries
Gromyko GA. Kardiologiia. 2014;54(3):4-8.
 157
patients, 60 with ICM and 97 with DCM
 Median follow-up 915 d
 12 cardiac deaths, 14 appropriate defibrillator
shocks, and 6 appropriate ATP
 Both percentage of LGE and NT-proBNP:

higher risk death or appropriate ICD activation
 These
markers in combination: identifying
individuals most benefit from this costly
intervention
 More specifically identification of a group at
lower risk, defer ICD implantation
Mordi I. 2014 Jun;7(6):561-9.
 403
primary prevention first ICD replacement,
275 (68%) no previous appropriate ICD
therapy
 Follow-up 86 m after initial implantation and
30 m after replacement.
 13.7%, 3-year incidence of appropriate ICD
therapy
 No predictors of appropriate ICD therapy
after replacement, including seven clinically
relevant factors
 Replacement recommended in all primary
prevention Pts despite no appropriate ICD
therapy in first battery service life
Yap SC. Heart. 2014 Aug;100(15):1188-92.

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Retrospective
Indications for continued ICD therapy at time of generator
replacement : LVEF ≤35% or receipt of appropriate device
therapy
231 patients, 59 (26%) no longer met guideline indications
for an ICD at generator replacement
Additional 79 patients (34%) had not received any
appropriate ICD therapies and had not undergone
reassessment of their LVEF
initial LVEF of 30% to 35% less likely to meet indications
for ICD therapy at the time of replacement (OR: 0.52; p =
0.01)
Patients without ICD indications subsequently received
appropriate ICD therapies at a significantly lower rate
than patients with indications (2.8% vs. 10.7% annually, p <
0.001)
Kini V. J Am Coll Cardiol. 2014 Jun 10;63(22):2388-94.



Dual-chamber ICD may improve specificity and reduce the risk of inappropriate
shocks, enhance AT/AF detection to permit stroke prevention, additional
expense and risk
100 Pts primary prevention ICDs randomized to dual-chamber or singlechamber followed for 1 year
Same programming in both groups:
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Delayed detection to avoid therapy for non-sustained episodes
High detection cut-off rates avoid treating slower, better tolerated arrhythmias
Minimized RV pacing
Routine use of supraventricular-ventricular tachycardia discriminators and ATP
One in each group (2%) inappropriate shock (P = 1.00)
Death in two patients in single-chamber, none of the patients in dual-chamber
(P = 0.15)
New AT/AF in 12 patients (24%) in the dual-chamber group, no patients in the
single-chamber group (P < 0.001)
mean cost dual- vs. single-chamber ICD $16 579 vs. $14 249, (P < 0.001)
No difference in QOL
Friedman PA. Europace. 2014 Oct;16(10):1460-8.
 With
optimal programming, inappropriate shocks
rare in primary prevention with both single- and
dual-chamber ICDs
 Routine use dual-chamber:

higher expense without reduced inappropriate shocks
or improved quality of life at 1 year
Friedman PA. Europace. 2014 Oct;16(10):1460-8.

Current mortality rate of Pts with prophylactic ICD
implantation

At 1, 2 and 5 years, 2.2 %, 4.2 % and 13.5 %2
At 1, 2 and 5 years, 2.4 %, 4.3 % and 14.7 %3
 Much lower as compared with older landmark trials

MADIT-II (16 % at 2 years)
 SCD-HeFT (29 % at 5 years)

Therefore, current guidelines for prophylactic ICD
implantation need reconsideration
 since it involves increased risks for these Pts and
high costs, need:

re-evaluate efficacy of ICD implantation
 better identify Pts who do not benefit from ICD

1- Luermans JG. Neth Heart J. 2014 Oct;22(10):429-30.
2- Verhagen MP. Neth Heart J. 2014.
3- Smith T. Clin Cardiol. 2011;34:761–7.
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