Should We Implant ICD In Patients With NICMP (Cons) NICM.pdf · • This was not surprising in an elderly population, it highlighted the importance of selecting patients for ICD implantation

Should We Implant ICD InPatients With NICMP (Cons)

Alireza Ghorbani Sharif, MD

Interventional Electrophysiologist

Tehran Arrhythmia Clinic

March 2018

Introduction

• Implantation of an ICD for primary prevention of SCD in patients with NICMP and EF < 35% has a Class I, level of evidence B. (European Guidelines)

• Implantation of an ICD for primary prevention of SCD in patients with ICMP and EF < 35% has a Class I, level of evidence A. (AHA and European Guidelines)

NICMP (Non-Ischemic cardiomyopathy), ICMP (Ischemic cardiomyopathy)

Europace (2017) 19, 660–664

Introduction

• The use of ICDs has been a major advancement in patients with ICMP with reduced ejection fraction <35%.

• The data supporting the use of ICDs are robust in patients with ICMP, limited randomized controlled clinical trial (RCT) data exist for similar benefit in patients with NICMP.

Circulation. 2017;135:201-203

ICD Trials

• A prior meta-analysis that included both primary and secondary prevention ICD trial in 2004 by Desai et al demonstrated a 31% reduction in all-cause mortality with ICD use in patients with NICMP.

• The data became the back bone of the current ACC/AHA guidelines for ICD implantation in patients with NICMP.

ACC/AHA (American College of Cardiology/American Heart Association)Circulation. 2017;135:201-203

ICD Trials in NICMP

• The history of the trials performed for ICDs, particularly in NICMP:

1. (Cardiomyopathy Trial) CAT

2. (Amiodarone Versus Implantable Cardioverter-Defibrillator

Randomized Trial) AMIOVIRT

3. (Prophylactic defibrillator implantation in patients with

NICMP) DEFINITE

4. (Sudden Cardiac Death in Heart Failure Trial) SCD-HeFT

DEFINITE Trial

• This was only one moderate-size trial has shown a trend to

mortality reduction in the NICMP population, but which did not

reach statistical significance.

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SCD-HeFT

• In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)

which compared conventional therapy with placebo,

amiodarone, or ICD in a population of ICMP and NICMP

patients, the mortality reduction associated with ICD

implantation was 23%.

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Result of ICD Trial in NICMP

• When it has been pretty well established in the community that ICDs reduce mortality?

• It was obvious that it can help in treating sudden cardiac death in patients with NICMP.

• Why did we need another trial for investigating of prophylactic ICD implantation in these patients?

We needed another trial because:

• The indication for primary prophylactic ICD in patients

with NICMP was based on small to medium-sized trials

with neutral outcomes (DEFINITE Trial).

• Positive effect of ICD confined to New York Heart

Association (NYHA) class II, and no patients received

concomitant CRT (SCD-HeFT).

We needed another trials because:

• Large proportion of these patients have been received CRT,

and the impact of ICD implantation in this setting is not well

known (SCD-HeFT).

• No trials have reported added benefit of ICDs in patients with

CRT.

• Medical therapy has improved since the ICD trials (SCD-HeFT).

• ICD implantation confers a risk of device-related complications.

This was probably an ideal time:

• Reassess the presence of ICDs on top of the medical

management?

• Did CRT confer an incremental benefit compared with

ICD or not?

DANISH Trial

• That was the background under which the DANISH trial was conducted, the trial started in 2007.

• DANISH trial investigated the effect of ICD implantation in patients with HF not caused by CAD who receive contemporary HF therapy including CRT.

The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

DANISH Trial• From February 7, 2008, to June 30, 2014, total of 1116 patients

were enrolled at five centers; 556 patients were randomly assigned to the ICD group, and 560 patients were assigned to the control group.

• The median follow-up period was 67.6 months (interquartile range, 49 to 85), and no patients were lost to follow-up for the primary outcome

• Follow-up data for all outcomes were available through June 30, 2016.


DANISH Trial

• The patients were divided into two groups:

1. First group receiving an ICD in addition to optimal medical management and CRT whenever indicated.

2. A second group did not receive an ICD but did get a CRT-Pif indicated, in addition to optimal medical management.

• In both groups, 58% of patients received CRT.


Characteristics of the Patients at Baseline

*Mineralocorticoid-receptor antagonistThe New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Inclusion criteria

• Clinical HF.

• Non-ischemic etiology.

• Optimal medical treatment.

• NYHA functional class II or III (patients in NYHA class IV could be included if planned for CRT).

• LVEF ≤35%.

• NT-proBNP 200 pg/mL (23.6 pmol/L).


Inclusion criteria

• Non-ischemic etiology was determined by coronary angiogram, although a normal computed tomography angiogram or nuclear myocardial perfusion imaging study was acceptable.

• Patients could be included despite having 1 or 2 coronary artery stenoses, if the extent of coronary artery disease did not explain the reduced left ventricular systolic function.

• Decision to implant a CRT device made before randomization.


Exclusion criteria

• Permanent AF (resting heart rate >100 beats/min).

• Uncorrected CHD or valve obstruction, obstructive CMP, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, and active vasculitis due to collagen vascular disease.

• On the urgent waiting list for a heart transplant.

• Major organ transplant.


Exclusion criteria (Contd)

• Receiving or having received cytotoxic or chemotherapy and/or radiation therapy for malignancy within 6 m before or clinical evidence of current malignancy, with the following exceptions: BCC of the skin, cervical intraepithelial neoplasia, prostate CA (if stable localized disease, with a life expectancy of 2.5 years in the opinion of the investigator).

• Known to be HIV positive, with life expectancy of less than 5 years.


Exclusion criteria (Contd)

• CKD treated with dialysis.

• Recent (within 3 m) history of alcohol or illicit drug abuse disorder, based on self-report.

• Any condition (eg, psychiatric illness) or situation that, in the investigator's opinion, could put the participant at significant risk.

• Lack of informed consent.


Methods (Contd.)

• Follow-up –

• 2 months.

• Every 6 months.

• Patients who receive ICD undergo regular follow-up by implantation center.

n engl j med 375;13 nejm.org September 29, 2016

DANISH Trial

• The real difference in the DANISH trial was that roughly 58% of patients in both arms had CRT devices.

• This was not a study of medical therapy vs. medical therapy and device as most of the previous studies have been.

• This was about:

• The best heart-failure therapy • The best drugs; add CRT to that• And then does a defibrillator help or not?


Primary Outcomes

• Death from any cause.


Secondary Outcomes

• Time to cardiovascular death.

• Time to sudden cardiac death.

• Time to resuscitated cardiac arrest or sustained ventricular tachycardia.

• Change in quality of life from baseline (Quality of life is assessed by the Minnesota Living with Heart Failure Questionnaire).


Primary outcome– Death from any cause

• When you look at the survival curve , at 2 years, you

start to see a separation: ICD was beneficial ,after 5

years, the survival curves start to converge.

• Older patents were starting to die from other causes.


Primary outcome– Death from any cause

• Primary outcome, death from any cause, occurred in 120 patients (21.6%) in the ICD group (4.4 events per 100 person-years) and in 131 patients (23.4%) in the control group (5.0 events per 100 person-years)

• The hazard ratio for death from any cause in the ICD group, as compared with the control group, was 0.87 (95% confidence interval [CI] 0.68 to 1.12; P = 0.28)


Secondary outcome– Sudden cardiac death

• The chance of sudden cardiac death in ICD group was about 50% less than in patients who did not have an ICD.

• Subgroup analysis, showed that patients younger than 68 years of age had mortality benefit from an ICD compared with older patients.


Secondary outcome– Sudden cardiac death

• Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P = 0.00


Mortality by age

Age – youngest two tertiles < 68 yearsAge – oldest tertile - ≥ 68 yearsP=0.009 for interaction with age


Secondary outcome– Cardiovascular Death

• Cardiovascular death occurred in 77 patients (13.8%) in the ICD group and in 95 patients (17.0%) in the control group (hazard ratio, 0.77; 95% CI, 0.57 to 1.05; P = 0.10)


Time to resuscitated cardiac arrest or sustained ventricular tachycardia

• The clinical outcome of resuscitated cardiac arrest or sustained ventricular tachycardia occurred with similar frequency in the two groups.


Discussion

• Prophylactic implantation of an ICD in NICMP did not provide an

overall survival benefit, although the risk of sudden cardiac death

was halved with ICD.

• Important interaction with age:

• Younger patients had a survival benefit with ICD.

• This was not surprising in an elderly population, it highlighted the

importance of selecting patients for ICD implantation carefully.


Discussion

• Younger patients and patients at higher risk more likely to had benefit from ICD.

• (MADIT II, clinical risk scores) would be very useful for identifying patients with NICMP, who are at high risk for death from arrhythmia similar to patients with ICMP.


Discussion

• In patients where the heart failure was less severe (New York Heart Association class II or class III), they were more likely to have tachyarrhythmia that lead to recurrent shock, VT storm, those kinds of things.

• Patients with more severe heart failure were more likely to have (pulseless electrical activity) PEA, bradyarrhythmic, or systolic failure.


Discussion

• 31% of deaths were due to non-cardiovascular causes.

• No difference of ICD between patients with CRT and

without CRT.


Discussion• The side effects associated with device implantation were not

trivial.

• Device related infections in 4.9% in the ICD and in 3.6% in the control (P = 0.29).

• Patients not receiving CRT, the risk of device infection was higher in the ICD group than it was in the control group.

(5.1% vs 0.8%) ( hazard ratio, 6.35; 95% CI, 1.38 to 58.87; P = 0.006).

• Inappropriate shocks in 5.9% in the ICD group.


Has the DANISH study changed your approach?

Post DANISH Trial era

• A questionnaire was provided via the Internet to the participating centers of the EHRA electrophysiology (EP) research network, and responses were collected during January 2017.

• In all, 48 centers from 17 different countries responded to the questionnaire. Of these, 80% were university hospitals, 12% were private hospitals, and 8% were non-university hospitals.

Europace (2017) 19, 660–664

Europace (2017) 19, 660–664

Results for patients with NICMP

Europace (2017) 19, 660–664

Results for patients with ICMP

What to Do Now?

• Can we take the results of this single trial and tell a patient, "You do not need ICD?”.

• Is this evidence strong enough to suggest that we should say an ICD is no longer warranted in NICMP?

• Are we going to change our practice?

• Are the guidelines going to change?

What to Do Now?

• Should we be considering CRT-P in NICMP patients first

because we see that, ejection fractions, for example,

improve?

CRT-P vs. CRT-D

• The diagnosis of NICMP was an important factor favoring CRT-P rather than CRT-D and was reported in almost one-third of centers. (COMPANION trial)

• Until now, no adequately powered study has provided evidence on the advantage of CRT-D vs. CRT-P.

• Recent registry suggested similar outcome in CRT-D vs. CRT-P, with the preference for CRT-P only similar to those described in this survey.

Conclusion

• Medical therapy is powerful and important, and our current guideline indicate patients need to be on good medical therapy before consideration for an ICD. (2017 ACC/AHA/HFSA )

• Highlights the role of resynchronization in NICMP if it has indication.

Open Discussion

• As far as future investigations are concerned, we need to come

up with a better marker to assess who will need an ICD beyond

the ejection fraction, beyond ECG.

• MRI and delayed enhancement. Some of this work is currently

in progress.

• So we need to figure out how to risk-stratify these patients

better?

Open Discussion

• Would we still offer an ICD or CRT-D for primary prevention in the

younger patients with NICMP?

• Won’t we implant ICD for primary prevention in older patients

with NICMP or who have comorbidities?

• Is CRT-P a first option if it has indication in these patients?

Tehran Arrhythmia Center

WWW.IranEP.org

[email protected]

Documents

Should We Implant ICD In Patients With NICMP (Cons) NICM.pdf · • This was not surprising in an elderly population, it highlighted the importance of selecting patients for ICD implantation