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Implantable Cardioverter-Defibrillators (ICDs) for the

Prevention of SCD: Appropriate Use in 2015

Andrew E. Epstein, MD

Professor of Medicine, Cardiovascular Division University of Pennsylvania

Chief, Cardiology Section

Philadelphia VA Medical Center Philadelphia, PA

Disclosures Research Grants:

Biotronik, Boston Scientific, Medtronic, St. Jude Medical Speaker’s Bureaus/Honoraria:

Biotronik, Boston Scientific, Medtronic, St. Jude Medical Advisor Relationships:

Boston Scientific, St. Jude Medical EP Fellowship Program Support:

Boston Scientific, Medtronic, St. Jude Medical

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Agenda

•  Why is there confusion; why this talk? •  What are the Guidelines for primary prevention

ICDs?

•  What are the data to support the Guidelines?

•  A few comments about CRT.

•  How do you handle individual patients?

Why is there confusion? Why this talk?

•  ACCF/AHA/HRS Device-Based Therapy GL •  ACCF/AHA HF GL

•  HFSA HF, ESC/EHRA and CCS GLs •  ACC Performance Measures •  HRS Statement on ICD indications not

represented in clinical trials •  Appropriate Use Criteria •  National Coverage Determination (NCD)

•  DOJ Investigation and Resolution Model

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Misunderstandings

•  The waiting time rules for primary prevention ICD implantation do not apply to patients with arrests (secondary prevention).

•  The time after MI which “counts” for a peri-MI arrhythmia is ≤48 hours. Arrests thereafter justify secondary prevention implantation.

Implantable Cardioverter-Defibrillators

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.

ICD therapy is indicated in patients with structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable.

ICD therapy is indicated in patients with syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiological study.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

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. J Am Coll Cardiol 2012;60:1297-1313.

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http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId= 110&ncdver=3&NCAId=148&NcaName=Implantable+Defibrillators&IsPopup=y&bc=AAAAAAAAEAAA&

http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId= 110&ncdver=3&NCAId=148&NcaName=Implantable+Defibrillators&IsPopup=y&bc=AAAAAAAAEAAA&

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AVID Primary Endpoint: Overall Survival (unadjusted)

Months Post Randomization

Surv

ival

0.0

0.2

0.4

0.6

0.8

1.0

0 12 24 36

ICD AAD

Percent Survival: ICD: 89.3% 81.6% 75.4%

AAD: 82.6% 75.1% 64.7%

N at risk: 1016 645 336 106

p = 0.012

The AVID Investigators. N Engl J Med 1997;337:1576.

Years

%

0 1 2 3 4 5 60

10

20

30

40

50

60

AVID/CASH/CIDS Cumulative Risk of Fatal Events

Total mortality Arrhythmic death

Amiodarone

Amiodarone ICD

ICD

Years

%

0 1 2 3 4 5 60

10

20

30

40

50

60

Connolly al. Eur Heart J 2000;21:2071.

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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.

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 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 nonsustained VT due to prior MI, LVEF less than or equal to 40%, and inducible VF or sustained VT at electrophysiological study.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

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

J Am Coll Cardiol 2012;60:1297-1313.

Crux of the Problem: Why is there a “waiting” period

post MI, CABG, PCI, and the diagnosis of HF?

•  At the time of initial evaluation… •  Stability of substrate unknown •  Responses to therapy unknown •  Device benefit uncertain

•  Waiting periods are based on RCTs that lead to guidelines and coverage decisions by private carriers and CMS/Medicare.

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Multicenter Automatic Defibrillator Implantation Trial II

(MADIT-II) •  Evaluated effect of prophylactic ICD therapy on

survival in patients with prior MI and LVD. •  Entry Criteria:

•  Chronic CAD with prior MI and LVEF ≤0.30 •  No requirement for NSVT or EPS •  No upper age limitation

•  Excluded if: •  MI <1 month •  Revascularization <3 months •  NYHA Class IV at enrollment •  Advanced organ system disease

Moss AJ, et al. N Engl J Med 2002;346:877-883.

ICD

Conventional

P = 0.007

1.0

0.9

0.8

0.7

0.6

0.0

Probability of Survival

0 1 2 3 4 Year

Survival in MADIT II

No. At Risk Defibrillator 742 502 (0.91) 274 (0.84) 110 (0.78) 9 Conventional 490 329 (0.90) 170 (0.78) 65 (0.69) 3

Reduction in death rate with ICD Rx: 12% at 1 yr, 28% at 2 yrs, 28% at 3 yrs

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For patients post MI, can I implant within 40 days after the event?

Defibrillator IN AMI Trial

Hohnloser SH, et al. N Engl J Med 2004;351:2481-2488.

•  Randomized comparison of OMT 6-40 days after MI with or without an ICD •  LVEF ≤35%, abnormal autonomic function (↓HRV or HR >80 bpm on monitoring)

Defibrillator in AMI Trial DINAMIT

Nonarrhythmic Death Arrhythmic Death

Hohnloser et al. N Engl J Med 2004;351:2481-2488.

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Immediate Risk-Stratification Improves Survival (IRIS) Study

Steinbeck G, et al. N Engl J Med 2009;361:1427-36.

•  Randomized comparison of ICDs vs. OMT 5-31 days after MI •  LVEF ≤40%, HR >90 +/- NSVT

N=902  patients

Moss AJ, et al. N Engl J Med 2002;346:877-883.

ICD

Conventional

P = 0.007

1.0

0.9

0.8

0.7

0.6

0.0

Probability of Survival

0 1 2 3 4 Year

Is Waiting a bad thing? Survival in MADIT II

No. At Risk Defibrillator 742 502 (0.91) 274 (0.84) 110 (0.78) 9 Conventional 490 329 (0.90) 170 (0.78) 65 (0.69) 3

Reduction in death rate with ICD Rx: 12% at 1 yr, 28% at 2 yrs, 28% at 3 yrs

Begin to diverge at 9 mos. and continue to separate

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Recovery of LV Function after Primary PCI for AMI

Ottervanger JP, et al. Eur Heart J 2001;22:785-790.

• Of patients with LVEF ≤40% on day 3, 24% improved to ≥40% at 6 months.

•  Improvement in 48% • Mean improvement 6%

• Deterioration in 25%

Prevalence of LVEF ≤40% at discharge and after 6 months

Incidence and Predictors of EF Improvement to >35% in Patients

Undergoing CABG (Minneapolis VAMC)

0

10

20

30

40

50

60

70

pre post pre post pre post

Ejec

tion

Frac

tion,

%

Overall Improved EF Unchanged EF n=74 n=38 n=36 .

Peri-operative change in LV Ejection Fraction

Q3-

Methods: • Of 2,838 patients who underwent isolated

CABG, 375 had echocardiographic assessment of LVEF before (within 6 months) and after (3-24 months) CABG.

• Of these, 74 (20%) had EF ≤35% prior to CABG and were examined.

Results: • Mean preoperative EF 28±6% improved

to 36±12% postoperatively (p< 0.001). Conclusion: •  More than 50% of the “ICD-eligible”

patients who underwent CABG with a preoperative EF ≤35% improved their EF to >35% after CABG.

•  Results support GL recommendation of reassessing EF 90 days after CABG in patients with low LVEFs. Koene RJ, et al. AHA Poster S4114, 2015.

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MADIT II: Time Dependence of ICD Implantation After

Coronary Revascularization •  MADIT II enrollment criteria

excluded patients with coronary revascularization within 3 months of MI

•  130 patients had PCI and/or CABG 3-6 months (median 4 months) prior to ICD

•  No reduction in all-cause mortality (or SCD) ≤6 months after revascularization

Goldenberg I, et al. J Am Coll Cardiol 2006;47:1811-7.

Conventional Rx ICD

For NICM, when does the clinical benefit start? Can I

implant at 3 versus 9 months?

3 Trials •  CAT •  SCD-HeFT •  DEFINITE

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CAT 1991-1997

DEFINITE 1998-2003

SCD-HeFT 1997-2001

Protocol OMT OMT +ICD

OMT OMT +ICD

OMT OMT +ICD OMT + amiodarone

n 104 458 2521

Entry Criteria NYHA II-III LVEF ≤30% Age 18-70 years

NYHA I-III LVEF <36% NSVT or ≥10 PVCs/hr

NYHA II-III LVEF ≤0.35

Duration of HF ≤9 months Not specified ≥3 months

NIDCM Primary Prevention Trials

• NYHA II-III chronic, stable CHF •  LVEF ≤0.35 • CHF ≥3 months

SCD-HeFT (NIDCM cohort)

Bardy G, et al. N Engl J Med 2005;352:225-237.

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What is the Optimal Waiting Period for NICM?

Study (HF duration diagnosis)

N <3 mos >3 mos <9 mos >9 mos

CAT (HF ≤9 months)

104 No No

DEFINITE (No duration)

458 “Yes” “Yes”

SCD-HeFT (HF >3 months)

1211 Not evaluated

Yes, “long” after Yes

CRT Indications Algorithm

J Am Coll Cardiol 2012;60:2604-5.

Colors  correspond  to  the  class  of  recommenda1ons  in  the  ACCF/AHA  Table  1.  

Benefit  for  NYHA  class  I  and  II  pa1ents  has  been  shown  in  CRT-­‐D  trials,  and  while  pa1ents  may  not  experience  immediate  symptoma1c  benefit,  late  remodeling  may  be  avoided  along  with  long-­‐term  HF  consequences.  There  are  no  trails  that  support  CRT-­‐pacing  (without  ICD)  in  NYHA  class  I  and  II  pa1ents.  Thus,  it  is  an1cipated  these  pa1ents  would  receive  CRT-­‐D  unless  clinical  reasons  or  personal  wishes  make  CRT-­‐pacing  more  appropriated.  In  pa1ents  who  are  NYHA  class  II  and  ambulatory  class  IV,  CRT-­‐D  may  be  chosen  but  clinical  reasons  and  personal  wishes  may  make  CRT-­‐pacing  appropriate  to  improve  symptoms  and  quality  of  life  when  an  ICD  is  not  expected  to  produce  meaningful  benefit  in  survival.  

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Foundation for the New Recommendations •  QRS morphology •  QRS duration

•  AF and outcomes

•  Co-morbidities

Slide sent by BS on Approval: Previously Published and Updated Results

•  MADIT-CRT met its end point in June 2009 and results published in the September 2009 NEJM online.

•  Results showed that CRT-D was associated with a 34% reduction in the relative risk of the primary end point.

•  Primary effectiveness end point achieved.

•  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.

Moss AJ, et al. N Engl J Med 2009;361:1329-38.

34% RR 57% RR

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Time to All-Cause Mortality or HF Event LBBB vs non-LBBB Subpopulations

Courtesy of Boston Scientific

57% RR 32% worse

QRSd and Survival: Meta-analysis

Cleland JG, et al. Eur Heart J 2013;on line.

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Sundaram V, et al. AHA, 2015.

Very Wide RBBB and CRT

Risk and Mortality in MADIT II: U-shaped Curve of ICD Efficacy

Goldenberg I, et al. J Am Coll Cardiol 2008;51:288-296.

•  Risk score model from MADIT II •  Constructed 5 risk factor model

•  Age >70 years •  NYHA class >II •  BUN >26 mg/dl •  QRS duration >120 ms •  Atrial fibrillation at baseline

•  Very high risk (VHR) patients: BUN ≥ 50 mg/dl and/or Cr ≥ 2.5 mg/dl (MADIT II excluded BUN ≥ 70 mg/dl and/or Cr ≥ 3.0 mg/dl).

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Identification and Characterization of Risk Factors for Atrial and Ventricular

Arrhythmias in CKD Patients Using an ILR

50 patients on dialysis •  Excluded patients with LVEF <35%, NYHA IV HF, PM, ICD, h/o VT or syncope •  Implanted with SJM implantable loop recorder (ILR)

Followed 12 ± 4 months, 6 deaths (12%) and 5 were unexpected •  All SCD events occurred in the 72 hour break between dialysis •  2 had autopsies w/o identifiable cause of death; 1 OOH witnessed CA w/o cause found •  ILRs showed SEVERE BRADYCARDIA AND ASYSTOLE RECORDED in 4 patients •  Interrogation of the 5th ILR was refused by the family.

Wong MCG, et al. J Am Coll Cardiol 2015;65:1263-1265.

Prevalence & Outcomes of Patients Receiving ICDs for PP Not Based on GLs

• Beth Israel Deaconess Medical Center, Boston •  17% received non-GL-based implants

– NGLB ICDs 12, 45, and 42 da post MI, revascularization or CM diagnosis (7.3% needed PM), respectively

– 1/125 within 40 day waiting period post MI or 3 mo post revascularization received appropriate therapy

Levine YC, et al. Am J Cardiol 2015;115:1539-1544.

Although these patients have similar long-term risk of receiving appropriate ICD therapy compared with patients with GB implants:

1. During waiting periods mandated by clinical practice GLs, risk is very low. 2. Results suggest little need to implant ICDs during waiting periods.

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Prevalence & Outcomes of Patients Receiving ICDs for PP Not Based on GLs

Beth Israel Deaconess Medical Center, Boston 17% received non-GL-based implants

•  NGLB ICDs implanted12, 45, and 42 days after MI, revascularization or CM diagnosis (7.3% needed PM), respectively

•  1/125 within 40 day waiting period post MI or 3 mo post revascularization received appropriate therapy

Levine YC, et al. Am J Cardiol 2015;115:1539-1544.

Although these patients have similar long-term risk of receiving appropriate ICD therapy compared with patients with GB implants:

•  During waiting periods mandated by clinical practice GLs, risk very low. •  Results suggest little need to implant ICDs during waiting periods.

http://www.modernhealthcare.com/article/20120721/MAGAZINE/307219994#

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The DOJ Investigation: ICDs not Pacemakers, CRT or otherwise

•  DOJ launched its investigation 8 years ago, not in response to the 2011 JAMA article.

•  DOJ Rationale: • Concern there was ICD implantation for reasons

not covered by the National Coverage Determination (NCD).

• Submitting a bill to Medicare for noncovered procedures can be considered Medicare fraud.

•  Liability is for both individual physicians and their hospitals.

Should We Be Surprised by the DOJ, CMS and the National Coverage Determination?

•  Probably not… •  We did the trials.

•  We defined the entry criteria.

•  We generated the data that led to the NCD.

•  Our societies (and we) ask for evidence- based medicine, why shouldn’t they?

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: WILL BE PURSUED WITH ENFORCEMENT and WITH OPTION FOR MULTIPLE DAMAGES.

DOJ “Buckets” 1.  No MI: Coded as MI but not 2.  PM/CRT needed, but not yet ICD-qualified

3.  Prior ICD: replacement needed w/in excluded time period

4.  “Associated with”: VT >48 hours post MI

5.  Technical violation (30-90 da post MI; 67-90 da post HF Dx)

6.  Syncope within waiting period

7.  Bridge to heart transplantation within waiting period

8.  Familial conditions: no prohibited time frames

9.  CRT: qualifies for CRT & other than waiting period ICD also

10. Previously qualified

WILL NOT BE PURSUED

Why not an ICD <3 months if LV dysfunction prior to MI?

•  Neither DINAMIT nor IRIS specified duration or prior history of ↓LVEF in entry or exclusion criteria.

•  Neither study included revascularization before enrollment in inclusion or exclusion criteria.

•  DINAMIT: •  1/3 had prior MI •  2/3 had thrombolytic therapy, PCI or both

•  IRIS: •  19% had prior MI •  72% had PCI

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Prior MI/LV Dysfunction in DINAMIT

•  Present in 32% of control group & 36% of ICD group •  Associated with 1.7X risk for death from any cause.

•  In ICD group, 51% of the patients with appropriate therapy had prior MI versus 33% of those with no appropriate therapy.

•  Patients with appropriate shocks had more HF (61% vs 49%) at baseline suggesting presence of pre-existing LV dysfunction.

•  Prior LV dysfunction/HF cannot be used to justify early implantation.

Dorian P, et al. Circulation 2010;122;2645-2652.

Why is there a lack of benefit early post MI?

•  SCD rate reduced with early reperfusion, BB, etc. •  ICDs convert SCD to non-sudden death.

•  “Sudden death” mechanisms differ early and late after MI with early increased risk for non-arrhythmic sudden (cardiac) death.

•  ICDs cause non-sudden death and risk counter-balances benefit.

•  ICD implantation (DFT testing) and altered autonomics dilute ICD benefit.

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AUC publications reflect an effort by the ACCF to critically and systematically create, review, and categorize clinical situations that may or may not be addressed in guidelines, and provide management guidance.

Appropriateness of ICD-CRT: Rating of Indications

•  7-9: Appropriate care •  Procedure is generally acceptable and is generally

reasonable for the indication

•  4-6: May be appropriate care (“uncertain”) •  Procedure may be acceptable and may be

reasonable for the indication

•  1-3: Rarely appropriate care (“inappropriate”) •  Procedure is not generally acceptable and is not

generally reasonable for the indication •  Does NOT indicate that the procedure should not be performed for that indication•  Does NOT indicate that the procedure should not be reimbursed for that indication

Courtesy of Dr. Andrea Russo

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Primary Prevention: CAD, Prior MI (>40 days) With Ischemic CM

Russo AM, et al. J Am Coll Cardiol 2013;61:1318-68.

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Viewpoint Conclusions: What are we to do?

•  Practice within the scope of the ICD NCD whenever possible. Conversely, inappropriate practice outside the GLs and AUC should not be tolerated.

•  Physicians who believe that a device is indicated in a situation not covered by the NCD must document their thought process and rationale.

•  Become involved with teaching coders about what we do, what constitutes a MI (not all troponin elevations represent an MI), and clearly state in charts when events occur, such as the diagnosis of heart failure and the initiation of GDMT.

Fogel RI, et al. J Am Coll Cardiol 2014;63:12-14.

Guidelines and Standard of Care “As with all clinical practice guidelines, the recommendations in this document focus on treatment of an average patient with a specific disorder and may be modified by patient comorbidities, limitation of life expectancy because of coexisting diseases, and other situations that only the primary treating physician may evaluate appropriately.”

Epstein AE, et al. J Am Coll Cardiol 2008;51:e1–62.

Epstein AE, et al. J Am Coll Cardiol 2008;51:2085-2105 (Executive Summary). J Am Coll Cardiol 2008;51:e1-e62.

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My Opinion and Experience •  FOLLOW THE GUIDELINES. It’s good protection. •  Do what’s right and document it -- you’ll be all

right. This is especially true in areas of controversy and in the absence of RCT data.

•  We have to be involved with coding education. •  For private carriers, a call by the responsible

physician and not a delegate to the Medical Director will virtually always assure coverage.

•  Although evidence drives GLs, AUC and CMS, GL indications are generally accepted by private carriers, but for CMS the NCD rules.