Download Primary Prevention ICD / CRT Task Force Report

Primary Prevention
ICD/CRT Task Force
Report & Recommendations
prepared for the
Ministry of Health and Long-Term Care
Chair
Hon. Wilbert J. Keon
Final Report
December 2004
December 2004
This report has been prepared for the
Ministry of Health and Long Term Care (MOHLTC)
no section of the report can be copied or reproduced without
the permission of the
MOHLTC
The Task Force wishes to thank the following individuals for
assisting the Task Force with its research:
Dr. Sean Tunis
Dr. Steven Phurrough
Dr. David Alter
Dr. Gillian Sanders
December 2004
TABLE OF CONTENTS
Executive Summary...........................................................................................................4
Introduction
Outline of the Issue..............................................................................................................8
What is known.....................................................................................................................9
Outstanding Issues – What is not known ..........................................................................11
Quantifying the ‘Need’ for ICD Therapy......................................................................13
The Approach ....................................................................................................................13
Estimation of Prevalent Population ................................................................................... 13
Estimation of Incident Population ..................................................................................... 15
Risk Stratification in Primary Prevention.......................................................................... 16
Ontario based Economic Analysis ................................................................................17
Current funding formula....................................................................................................19
Budget impact....................................................................................................................19
Cost Effectiveness analysis ...............................................................................................20
Cost Effectiveness ............................................................................................................. 20
Limitations.........................................................................................................................21
Recommendations............................................................................................................22
Index of Tables
Table 1 Source of Estimates of Prevalent Heart Failure Population ................................. 14
Table 2 Primary Prevention Population ............................................................................ 16
Table 3 Risk Stratification Criteria....................................................................................18
Table 4 Meta Analysis of Primary Prevention Trials........................................................ 21
Index of Appendices
Appendix I Committee Structure & Terms of Reference.................................................. 24
Appendix II Summary of Primary Prevention Trials ........................................................ 26
Appendix III ICD Actual, Projected & Recommended Volumes ..................................... 29
Appendix IV Ontario Advanced Arrhythmia Centres & Future Capacity ........................ 31
Appendix V Literature Review .........................................................................................32
Appendix VI Estimating Ontario’s ICD Need ..................................................................35
Appendix VII Determination of Unrelated Health Care Costs and Cost Effectiveness....44
Appendix VIII ICD Registry Referral Form ..................................................................... 45
References .......................................................................................................................48
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December 2004
EXECUTIVE SUMMARY
An Implantable Cardioverter Defibrillator (ICD) is a device implanted under the skin that
delivers energy discharges or shocks to the heart to terminate a fast chaotic heart rhythm. These
irregular heartbeats (usually ventricular arrhythmias), often triggered by acute coronary events
or structural heart abnormalities, are a major cause of sudden cardiac death (SCD). In Canada,
SCD is credited for over 35,000 deaths annually. Thirty to fifty percent of deaths classified as
SCDs occur in individuals who have never been diagnosed with cardiac disease.
The Ministry of Health and Long-Term (Ministry) through the Acute Services Division’s
Priority Services Unit, has provided dedicated funding for ICD technology since 1988. In
2003/04 the eight designated advanced cardiac arrhythmia hospitals in Ontario performed 1,154
ICD implants at a cost in excess of $32M.
Since 2002, seven clinical trials (MADIT II, CAT, AMIOVERT, COMPANION, DEFINITE,
SCD-HeFT, DINAMIT) have reported on prophylactic or ‘preventive’ ICD use in individuals
with ischemic and non-ischemic heart disease and impaired heart function. Two trials in
particular (MADIT II and SCD-HeFT) reported improved mortality with prophylactic ICDs.
These studies collectively support the expanded use of ICDs to patient populations beyond
those with known life threatening arrhythmias (e.g. victims of SCD that have been resuscitated)
or with major cardiac risk factors. As a result of these studies, the pressure to use ICD
technology for the primary prevention of SCD has grown dramatically. For funders and policy
makers, the prospect of an enormous increase in the numbers of patients who may now be
eligible for a very expensive medical procedure in the absence of longer trials, definite costeffectiveness studies and certainty about the patients who would most benefit from this therapy
is sobering.
In early 2004, the Assistant Deputy Minister of Health, Acute Services Division, established
the ICD/CRT Task Force to better identify the target population that would realize the greatest
survival benefit from ICD therapy and to assess the budget impact of such a policy change in
Ontario. Recommendations from the Cardiac Care Network of Ontario, submitted in 2002
advised the ministry to invest in excess of $75M over four years to support ICD technology
based on MADIT II criteria. CCN’s recommendations did not include the potential patient
population that was suggested as a result of the SCD-HeFT trial.
The Task Force met six times over a seven month period and performed a comprehensive
review of the available literature, considered information from other jurisdictions and met with
representatives from the US Centers for Medicare and Medicaid Services (CMS). The efforts
of the Task Force were essentially focused on three core objectives:
1. Quantifying the Need for Primary ICD therapy in Ontario.
2. Risk Stratifying the Cardiac Care Population that appeared to most benefit from ICD
therapy.
3. Completing an Economic Analysis on primary ICD therapy in the Ontario context.
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December 2004
The Task Force commissioned the Institute for Clinical Evaluative Sciences (ICES) to help
quantify the total number of heart failure patients in Ontario who theoretically would be
candidates to receive ICD therapy. This estimate employed similar eligibility criteria used by
the most recent clinical trials. Using the only available provincial clinical data and based upon
a number of key assumptions, ICES estimated Ontario’s prevalent heart failure population who
may be ‘theoretically’ eligible for prophylactic ICD therapy to be approximately 23,700 at the
low end and 86,000 at the upper range. From this analysis an incident heart failure population
of 2,488 patients was estimated all of whom would be technically ‘eligible’ for prophylactic
ICDs. This estimate included the patients that today are receiving an ICD for primary
prevention.
To assist providers screen those patients who would benefit the most from prophylactic ICD,
the Task Force developed objective risk stratification criteria for primary ICD and ICD/CRT
use based upon available evidence from the five primary prevention trials. A left ventricular
ejection fraction (LVEF) of less than 30% and the inclusion of only those patients that have
been optimized on medical therapy were used to risk stratify the population. The Task Force
recommended the following detailed criteria:
Inclusion Criteria:
ICD:
•
Ischemic or non-ischemic cardiomyopathy combined with:
Left ventricular ejection fraction (LVEF) <30% measured by radionuclide angiography
(RNA) within 2-3 months of ICD implant, and
• Optimized medical therapy that includes betablockers, ACE inhibitors, ARBs, statins
and aspirin for at least 3-6 months prior to implant
Selected high risk patients with one of the following conditions may be considered:
•
Hypertrophic cardiomyopathy
•
Long QT syndrome
•
Arrhythmogenic right ventricular dysplasia (ARVD)
•
Congenital heart disease
•
Brugada’s syndrome
Patient must be able to give own consent
•
•
•
ICD/CRT:
Ischemic or non-ischemic cardiomyopathy
NYHA heart failure Class III-IV, despite optimal medical therapy as described above
QRS >120 msec
Ejection fraction <30% measured by radionuclide angiography (RNA) within 2-3 months of
ICD implant or LVEF <35% and referred through a heart failure program.
•
•
•
•
Exclusion Criteria
• Cardiac disease with high probability of pump failure death where survival is not expected
to be altered by defibrillator therapy
• Patients who would benefit from cardiac surgery (bypass or valve replacement) or multivessel coronary angioplasty. These patients should be considered for revascularization and
if revascularized, should be reassessed 3-6 months post procedure.
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December 2004
•
•
•
Documented MI or a new diagnosis of heart failure within 6 months of implant. These
patients should be reassessed after medical optimization unless clear indication for ICD
therapy i.e. documented sustained VT.
Presence of a systemic disease that would shorten life expectancy (< 2 years) or an existing
DNR order. (systemic disease i.e. metastatic cancer, cirrhosis)
Presence of co-morbid illness, such as:
• Chronic renal failure requiring dialysis (primary prevention).
• Irreversible brain damage from pre-existing cerebral disease (i.e. debilitating
CVA/Dementia)
• Major psychiatric disease, (ETOH abuse, drug abuse)
• Chronic pulmonary disease requiring home oxygen for palliation
Finally, the budget impact and cost effectiveness of prophylactic ICD therapy in the Ontario
context was assessed. The economic analysis generated a crude budget impact for both the
incident and prevalent patient population. The budget impact for the prevalent population
ranged from $770M to $2.4B based upon a low prevalent range of 23,700 patients to a high of
86,400 patients. Using the incident population of 9,575 derived from hospital admission
discharge data, the budget impact for the incident population was estimated at $311M. After
MADIT II and SCD-HeFT criteria were applied to the Ontario data an estimated budget impact
of $71M was projected. This wide variation in budget requirements reflected the insufficient
data available to the Task Force. However, the task force members felt that the most likely
scenario is one that represents the highly specific incident population and an incremental
budget requirement of $71M.
Ontario based cost effectiveness (CE) estimates were calculated using the results and estimated
survival benefits associated with the MADIT II and SCD-HeFT trials. The incremental cost of
adjusted life years was identified as:
• $17,568 per life year (LY) and $24,436 per quality adjusted life year (QALY) for MADIT
II population, and
• $23,678/LY and $32,936/QALY for SCD-HeFT population.
To make the analysis complete it was necessary to account for the level of uncertainty
surrounding these estimates. To accomplish this, the analysis followed guidelines that
supported including unrelated health care costs incurred during the period of life years gained
from an ICD (an average .6 –1.84 QALYs). A maximum cost of $121,000 - $170,000 per
QALY was calculated.
The lack of available data on long term outcomes, the transferability of the clinical trial results
and the overly broad patient study inclusion criteria, challenged the development of a robust
risk stratification scheme. To address these data and outcome concerns, the Task Force
supported the establishment of an ICD database that would allow the collection of objective
and reliable information to better inform future decisions related to this technology, and to
describe the use and outcomes of ICDs in Ontario.
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December 2004
The Task Force recommends the following actions to fulfill the ADM’s request:
1. That the MOHLTC consider an annual ICD growth rate of 30% until a total of 3,350 ICD
devices are supported annually for primary and secondary purposes. This represents an
incremental increase of 2,181 ICD devices for primary prevention purposes annually over
the volume completed in 2003/04.
2. ICD/CRT therapy has been demonstrated to be beneficial to a select heart failure
population. While there is no evidence to identify an ideal volume, to ensure the
availability of this technology, the task force recommends that the MOHLTC and Ontario’s
advanced arrhythmia centres plan that 30% of their ICD volumes will be combined
ICD/CRT devices.
3. That Ontario arrhythmia centres that implant ICD and ICD/CRT devices for primary
prevention purposes should do so in consideration of the “risk stratification
inclusion/exclusion criteria” identified by the Task Force.
4. That the MOHLTC support an ICD database that is linked with an administrative database
such as that which exists at ICES for the purposes of monitoring utilization, patient
characteristics, uptake and long term outcomes. In addition, hospitals that are funded to
provide ICD services be expected to collect and report ICD data to a central database. The
data collected for the database should at a minimum encompass those data elements listed
on the referral form provided in appendix VIII. In addition, Ontario should explore the
opportunity of developing a relationship with CMS for the purpose of comparing outcome
data.
5. That ICD data and new clinical evidence be reviewed annually to incorporate new
information about ICD effectiveness, and to refine risk stratification criteria.
6. That ICD and ICD/CRT devices be inserted at advanced arrhythmia centres with the
involvement of a cardiac electrophysiologist. Decisions to insert an ICD/CRT device
should include a heart failure specialist. Additionally, Ontario ICD centres must insert a
minimum of 100 devices annually. New ICD centres must insert a minimum of 50 ICD
devices annually and these services should be reviewed annually to assess their ongoing
viability until they insert 100 devices annually.
7. That the MOHLTC assess the necessary infrastructure (capital and human) to meet the
recommended projected demand for ICD and ICD/CRT technology.
8. That the MOHLTC revise the current ICD funding rate to reflect changes in practice,
expanded clinical criteria, replacement devices and follow up costs.
7
December 2004
Outline of the Issue:
Sudden cardiac death (SCD) refers to death resulting from an abrupt loss of heart function and
is credited for 35,000 - 40,000 Canadian deaths annually 1 . The majority of SCDs are caused by
ventricular arrhythmias (irregular heartbeats that lead to chaotic electrical heart activity
resulting in sudden cardiac death), often triggered by acute coronary events or in association
with structural heart abnormalities. 2 Thirty to fifty percent of deaths classified as SCDs occur
in individuals who have never been diagnosed with cardiac disease 3 .
Prevention of SCD is classified as either primary, (before an individual has experienced a life
threatening arrhythmia and for prophylactic purposes), or secondary (prevention of a
reoccurrence of a life threatening arrhythmic event in patients with unstable cardiac
arrhythmias or who have survived a cardiac arrest).
The Ministry of Health and Long-Term (Ministry) has provided dedicated funding to support
the use of Implantable Cardioverter Defibrillator (ICD) technology in patients who have
experienced life threatening arrhythmias (secondary prevention) since 1988.
In 2002, investigators for the Multicenter Automatic Defibrillator Implantation Trial II
(MADIT II -2002) 4 reported that the primary or prophylactic use of ICDs in patients with prior
myocardial infarction and poor left ventricular function (but no documentation of life
threatening arrhythmias) reduced all cause mortality by 31%. Clinical uptake of the MADIT II
criteria was immediate and utilization increased dramatically.
In December 2002, the Cardiac Care Network of Ontario (CCN) recommended that the
Ministry expand ICD funding to support an expanded patient population based on MADIT II
criteria. CCN recommended that the ministry support an ICD therapy increase of 300% over
four years 5 . CCN’s recommendation was based on incidence data and did not address the
prevalent patient population in Ontario.
In March 2004, investigators for the Sudden Cardiac Death in Heart Failure Trial, (SCD-HeFT)
reported that prophylactic use of ICD therapy reduced all cause mortality by 23% in heart
failure patients with and without a history of ischemic heart disease 6 .
Both the MADIT II and SCD-HeFT trials captured a broad range of patients. Many
governments have become concerned about the sustainability of these services given the
expanded eligible population identified by these trials. Policy makers require a way of risk
stratifying patients that would most benefit from this technology.
In April 2004, the Assistant Deputy Minister of Health invited Dr. Keon, then the Chief
Executive Officer of the University of Ottawa Heart Institute, to chair a task force to advise the
ministry on strategies to effectively manage the demand for ICDs in Ontario. The task force
structure, terms of reference and work plan are provided in appendix I.
8
December 2004
What is known:
•
ICD technology is an effective treatment to prevent SCD in patients who have experienced
life threatening ventricular arrhythmias (secondary prevention). Secondary prevention
trials undertaken in the early 1990s (AVID, CASH, CIDS) supported the use of ICD
technology in high-risk patients. 7 8
•
Primary prevention studies conducted in the late 1990’s (MADIT, CABG-Patch, MUSTT)
reported reduced mortality with ICD use. However, methodological issues in the design of
these studies made a generalized and conclusive interpretation difficult 9 (7) (see appendix II
for a summary of primary prevention trials).
•
Both MADIT and MUSTT reported on a specific ‘high risk’ subgroup of patients who have
inducible sustained ventricular arrhythmias on EP testing. The use of ICD technology in
this population as a preventive treatment for SCD is an accepted practice , endorsed by the
Canadian Cardiovascular Society, the European Society of Cardiology and the American
Heart Association. 10 (7,8)
•
A recent clinical trial (DINAMIT) reported that prophylactic use of ICD therapy in patients
with a recent heart attack (<40 days) and poor heart function did not reduce all cause
mortality. 11
•
Since 2002, two primary prevention studies (MADIT II, SCD-HeFT) have reported
statistical significant reductions of 31% and 23% respectively in all cause mortality. The
former study evaluated patients who had a prior myocardial infarction (> 1 month) and left
ventricular systolic dysfunction (LVSD), and the latter evaluated patients with heart failure
and LVSD. In MADIT II 87-88% of the patients enrolled had an interval of greater than 6
months between enrollment and previous myocardial infarction (4). MADIT II and SCDHeFT were designed with simple inclusion criteria, with no attempts to risk stratify
patients. 12 (9)
•
In the United States following the release of SCD-HeFT’s findings, clinicians and
manufacturers demanded that the Centers for Medicare and Medicaid Services (CMS)
revise the June, 2003 CMS decision memo. This memo applied a QRS duration qualifier to
the MADIT II criteria.
•
In October 2004, CMS issued a draft memo that expanded ICD coverage to patients with 1)
ischemic dilated cardiomyopathy, previous documented heart attack and left ventricular
ejection fraction (LVEF) of < 30% and 2) non-ischemic dilated cardiomyopathy LVEF of <
30% with the qualifier that these patients had to be enrolled in a FDA approved clinical trial
and a national registry 13 . This decision reversed CMS’s 2003 ruling that required a QRS
qualifier to the MADIT II criteria.
9
December 2004
•
In October 2004, the Canadian Cardiovascular Society/Canadian Heart Rhythm Society
presented a draft position paper that recommended ICD use in patients with 1) ischemic
dilated cardiomyopathy and LVEF of < 30% (Class I) and 2) non-ischemic dilated
cardiomyopathy and LVEF of < 30% (Class IIa). 14
•
Patients with reduced left ventricular function appear to benefit the most from ICD
therapy. 15 (7)
•
To date, primary ICD studies have focused on individuals with left ventricular dysfunction,
a subset of the SCD population.
•
Cardiac Resynchronization Therapy (CRT) is an emerging technology for patients with
severe heart failure with left ventricular dysynchrony. CRT provides early stimulation to
the most delayed area of activation of the left ventricle, allowing more synchronous pacing
of both ventricles to improve left ventricular mechanical function.
•
There is a subset of heart failure patients that may clinically benefit from combined ICD
and CRT technology. In 2004, the COMPANION trial reported a 36% and 24% reduction
in all cause mortality with CRT/ICD and CRT devices respectively in severe heart failure
patients. 16
•
CRT/ICD therapy is diffusing in Ontario. While the ministry has not approved dedicated
funding for CRT devices, CCN’s data reflects that hospitals with approved ICD services are
implanting combined CRT/ICD devices and submitting this activity as part of their ICD
volumes. 17
•
CCN data reports that in 2003/04, 67% of all ICDs were new devices, 20% were
replacement and 13% were CRT/ICD devices. (17)
•
All patients with ICDs or ICD/CRT devices require periodic follow up to ensure optimal
device functioning. This includes; monitoring of device function, optimizing device
performance for maximum efficiency and longevity, minimizing complications and
anticipating replacement of system components. (15)
•
ICD device longevity is dependent on a number of factors that include use of the device
(e.g. number of shocks delivered, use of alternative modalities such as pacing), lead
integrity, lead compatibility and implant damage. Based on reports from industry and
expert opinion, ICD device longevity ranges from 5-10 years depending on the use and
model of the ICD. 18 19
•
ICD implantation has demonstrated an average annual growth rate of 26% from 1998/99 to
2003/04. Replacement devices account for 14-19% of the total ICD devices inserted
annually (Table A, Appendix III).
•
In 2002, CCN advised the ministry that a further 2,288 ICDs would be required by 2006/07
based on MADIT II criteria (refer to figure 1, Appendix III for growth scenarios) (5).
10
December 2004
•
In Ontario the provision of ICD technology is restricted to advanced cardiac centres that
have the expert resources necessary to diagnose, treat and manage patients with complex
arrhythmias (Table A, Appendix IV). The American College of Cardiology/American
Heart Association/ North American Society for Pacing and Electrophysiology
(ACC/AHS/NASPE) 2002 practice guidelines specify that an ICD service requires the
involvement of a trained electrophysiologist. (15)
•
The existing advanced arrhythmia centres’ infrastructure will require capital expansion to
meet the volumes suggested by either growth scenario (Table A, Appendix IV). 20
•
A 2004 survey of Ontario’s eight advanced arrhythmia cardiac centres identified that thirtythree cardiac electrophysiologists are in clinical practice at these centres. 21
•
The current ministry reimbursement rate for ICD procedures ($32,500) was developed
based on 1997/98 costing data 22 and prior to the indication of ICD technology as a primary
prevention treatment modality.
•
Patients receiving ICDs for prophylactic purposes or as a replacement can be discharged the
same day or within 24-48 hours of implantation. 23
•
Ontario’s reimbursement rate is the highest among those provinces that provide dedicated
funding for ICD procedures. 24
•
There is no existing database that is available to objectively monitor the patient population
that is now being prescribed prophylactic ICD therapy compared to the patient population
identified by the recent studies.
Note: Refer to appendix V for details of literature review undertaken by the ICD Task Force.
Outstanding issues (What is not known):
•
Valid and reliable risk stratification tools to identify those patients most likely to benefit
from ICD or CRT/ICD therapy 25 (3) and the value of electrophysiology studies (EPS) in
identifying those patients at high risk of SCD.
•
The budget impact and cost effectiveness of ICDs as a primary prevention therapy in the
Ontario context in 2004. Blue Cross and Blue Shield Association (BCBSA) published a
cost effectiveness analysis of ICD therapy compared to conventional therapy in the MADIT
II population. BCBSA analysis determined that ICD use in patients who met the MADIT II
trial criteria increased life expectancy by 1.85 years or 1.33 years quality adjusted life years
(QALY). The incremental cost effectiveness ratio based on this data is $36,700 per LY and
$50,900 per QALY. 26
•
The long term outcome/benefit of primary prevention ICD therapy (9). Information on the
long-term outcome of prophylactic ICD use is limited to the data reported in clinical trials.
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December 2004
The morbidity and expense associated with implantation, battery changes and inappropriate
shocks in patients who do not benefit from prophylactic ICD therapy is unknown 27 .
MADIT II reported worsening heart failure in the ICD population, CABG-patch reported
increased infection in the ICD group and DEFINITE reported that 21.4% of patients in the
ICD group received inappropriate shocks.
•
The skill and resources necessary to manage the implantation and maintenance needs of
patients receiving prophylactic ICD therapy. CMS’s 2004 draft decision memo reported
that both the American College of Cardiology (ACC) and Heart Rhythm Society support
the continued clinical practice of threshold testing for ICD therapy(13).
•
The impact of medication compliance on the incidence of SCD. The DEFINITE
investigators questioned whether patient’s high compliance rate (85%) with their oral
medication in the standard group contributed to the fact that the study failed to reach a
statistical significant reduction in all cause mortality. 28 In addition, it has been suggested
that the optimal medical therapy provided in all of SCD-HeFT treatment arms was a factor
in reducing overall mortality in all groups (13).
•
The appropriate replacement rate for primary prevention devices. The longevity of new
ICD devices, dependent upon usage and model, is estimated to be 7-10 years. It is
unknown from the clinical trials whether the replacement rate for ICDs used for primary
prevention purposes will track current practice.
•
The published report from the SCD-HeFT trial is not yet available.
•
The population in Ontario, that based on MADIT II and SCD-HeFT criteria, would be
eligible for prophylactic ICD therapy
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December 2004
Quantifying the ‘Need’ for ICD Therapy
In determining Ontario’s eligible heart failure population for primary prevention ICD therapy,
the task force made the following predeterminations:
•
•
•
•
•
The analysis would be restricted to MADIT II and SCD-HeFT study eligibility patient
criteria.
That there is a subset of cross over patients in the heart failure population that will be
captured with MADIT II and SCD-HeFT criteria.
Individuals who experienced SCD but also have a LVEF > 35% (victims of, or at high risk
for SCD with no previous cardiac history or individuals with cardiac conditions exclusive
of heart failure that are high risk of SCD i.e. long QT syndrome) will not be captured by
this criteria.
A reasonable estimation of the heart failure population in Ontario is possible through
combining heart failure admissions reported through the Canadian Institute for Health
Information (CIHI) discharge database with the data from the Ontario Health Insurance
Plan (OHIP) database.
In the absence of a published peer review article the task force adopted the inclusion and
exclusion criteria documented in Appendix VI, Table 5, as a reasonable representation of
the SCD-HeFT criteria to apply to clinical data collected as part of the Enhanced Feedback
For Effective Cardiac Treatment (EFFECT) study 29 .
Approach:
The analysis to quantify the estimated population in Ontario that may be eligible for ICD
therapy based on MADIT II and SCD-HeFT was conducted by the Institute for Clinical
Evaluative Sciences (ICES). ICES estimated Ontario’s heart failure population from both a
prevalence and incidence perspective (see appendix VI for details of the analysis).
The salient inclusion criterion in both MADIT II and SCD-HeFT was left ventricular ejection
fraction (LVEF). Since, data on LVEF is not available in existing public administrative
databases, ICES used CIHI’s discharge database, the OHIP database, the Canadian Community
Health Survey and the EFFECT database to complete their analysis.
Estimation of Heart Failure Prevalence:
To determine the potential number of Ontarians that could be considered for an ICD, it was
necessary to first identify the relative prevalence of left ventricular systolic dysfunction
(LVSD) in the community. A literature search for population-based estimates of LVSD
identified six studies (Appendix VI) with a range of similar thresholds of left heart function
(LVEF ranged from < 40% -50%). Weighted together these studies suggested that 53% of
heart failure patients have poor heart function (referred to as low ejection fraction).
Several approaches were explored to arrive at an estimate of Ontario’s heart failure population:
• Redfield et al 30 identified a population based prevalence through detailed
echocardiographic assessment. This study concluded a prevalence rate of approximately
1% for persons with LVEF < 35% and approximately 0.5% for < 30%. Applying this
13
December 2004
•
•
•
finding to Ontario’s population suggests approximately 43,200 Ontarians have an LVEF <
30%.
A review of CIHI’s discharge abstract database identified that approximately 17,000
patients were admitted to acute care hospitals in 2001/02 for heart failure. Of these 9,575
patients had no prior heart failure admissions and were identified as unique, newly admitted
patients with heart failure. Since the hospital discharge data does not include the heart
failure population cared for in the community who may never get admitted this number is
likely an underestimation.
To identify the number of heart failure patients cared for in the community, ICES examined
physician fee reimbursement for heart failure diagnosis in the OHIP database. The review
identified that in 2001/02 over 60,000 unique patients sought medical attention for heart
failure. Applying the community based estimate of LVEF (53%) identified through the
literature search would suggest that over 30,000 patients in Ontario have an LVEFs < 4050%.
The estimated prevalence of heart failure in Ontario was also informed through a review of
the Canadian Community Health Survey, conducted by Statistics Canada 31 , which reported
a heart failure prevalence of 1.17% for individuals > 20 years of age. If extrapolated to
Ontario’s population this captures 101,000 individuals. Applying the community based
estimate of LVEF (53%) to this population suggests that 50,500 Ontarians have an LVEF <
40 –50%.
The methods described above illustrate the potential magnitude of heart failure cases in
community based populations. However, population based prevalence estimates are not likely
to mean that patients with this condition will seek medical care. A more refined estimate of the
Ontario specific need was conducted by using data collected by Alter et al 32 from a sample of
echocardiographic (echo) studies drawn from a diagnostic laboratory in 2001. In this study, the
prevalence of LVEF < 35% was 8.3% of all patients undergoing echocardiography. If this
prevalence estimate is generalized to all patients undergoing echocardiography there would be
23,700 patients with left ventricular systolic dysfunction (in a cross sectional sample of 2001).
Table I summarizes the range of estimates for prevalence of heart failure in Ontario obtained
through the analyses discussed above.
Table I
Source of Estimates for the Prevalent Heart
Failure (HF) Population
HF population from OHIP data base
HF population from Canadian Community
Health Survey
HF population from Redfield analysis
extrapolated to Ontario’s population
HF population, Ontario specific from Alter et al
echo analysis
Estimated Ontario’s Population
•
•
30,000 (LVEF < 0.4-0.5)
50,500 (LVEF < 0.4-0.5)
•
•
•
86,400 (LVEF < .35)
43,200 (LVEF < .30)
23,700 (LVEF < .35)
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December 2004
Limitations of Prevalence Estimates:
The methods used in the analysis described above attempts to predict the potential pool of
patients in Ontario who may be eligible for ICD based primarily on left ventricular ejection
fraction (LVEF). It did not apply the specific exclusion criteria that were employed by the
MADIT II and SCD-HeFT investigators or CMS.
Estimation of the Incident Population Eligible for Primary ICD based on Clinical Trial Criteria:
This approach utilized data from patients hospitalized with acute myocardial infarction and
congestive heart failure from acute care hospitals in Ontario collected as part of the EFFECT
study (29). This data set contains substantial clinical detail and is comprised of two disease
subcategories, patients with acute myocardial infarction (EFFECT-MI) and patients with
congestive heart failure (EFFECT-HF). MADIT II and SCD-HeFT inclusion and exclusion
criteria were applied to the heart failure patients in EFFECT-MI and EFFECT-HF where
applicable. Since the details of SCD-HeFT were not available, the task force agreed to use the
inclusion and exclusion criteria that were available on the investigators website as shown in
Table 5, Appendix VI. To determine the incident cases of patients that may require ICDs in
Ontario, the ratio of candidates from EFFECT was applied to the heart failure patients in
Ontario.
The CIHI discharge abstract database was used to identify the number of heart failure patients
admitted with no prior heart failure admissions and the number of patients admitted with an
acute myocardial infarction (AMI). In 2001/02 there were 9,575 heart failure patients and
17,297 AMI patients identified.
The task force recognized that reduced LVEF was one of the major criteria used in the trials.
The majority of Ontario hospitalized patients (approximately 50%) do not undergo an
assessment of heart function. The task force developed two scenarios to address this heart
function data shortcoming. One scenario assumed that those patients that did not undergo
diagnostic testing did not have reduced heart function (conservative). The second scenario
assumed that those patients who were not assessed had similar results to those who were
assessed (liberal). Since many Ontario hospitals do not have access to echocardiography
resources, the task force chose the liberal approach to determine the potential population
eligible for Primary ICD.
In 2003, CMS decided in favor of including a QRS qualifier to the MADIT II criteria for ICD
coverage. CMS based this decision on an analysis of MADIT II data, which showed that
patients with QRS < 120 ms had a small, not statistically significant, reduction in mortality
compared to the conventional therapy group. Early reports from the SCD-HeFT investigators
indicate ICDs are beneficial regardless of QRS width (23). The ICD task force concluded that
there was insufficient evidence to support prolonged QRS as a qualifying indicator for ICD
eligibility.
The task force discussed the appropriateness of using the EFFECT MI dataset in view of
DINAMIT trial results, which reported no benefit of prophylactic ICD use in recent MI patients
(11). The task force also recognized that left ventricular function at the time of the acute
15
December 2004
myocardial infraction (AMI) may not reflect its function in the longer term. For these reasons
the ICD Task Force limited its analysis to the EFFECT-HF data set.
Applying MADIT II and SCD-HeFT criteria to the EFFECT-HF data set, within the parameters
described above, resulted in 892 and 2,521 patients meeting the MADIT II and SCD-HeFT
criteria respectively.
The task force recognized that applying both the MADIT II and SCD-HeFT criteria resulted in
a degree of overlap between the two populations. To eliminate this overlap an adjustment was
incorporated into the analysis. The proportion of heart failure patients with LVSD who met
only SCD-HeFT criteria was 63.3%.
The incident heart failure population that was determined to be potentially eligible for ICD
therapy based on MADIT II and SCD-HeFT criteria was calculated to be (2,521*63.3%) + 892
= 2,488.
In the absence of explicit data that reports primary diagnosis for ICD implantation, the Task
Force estimated that 33% of new ICD implants are currently being inserted for primary
prevention therapy 33 . The number of ICDs currently implanted for primary prevention
purposes were deducted from the incident primary prevention population identified above refer
to table II.
Table II
ƒ ICD annual volume (2003/04) 1,166 – 233 ICDs (replacement devices) = 933
new ICDs
ƒ 933 new ICD * 33% = 307 ICDs inserted for primary prevention purposes
currently
ƒ 2,488 – 307 = 2,181 patients potentially eligible for ICD therapy based on
MADIT II and SCD-HeFT criteria
The Task Force concluded that an estimated incremental 2,181 new incident patients would
appear to be a reasonable estimate of the additional annual ICD volumes that would be required
to satisfy the MADIT II and SCD-HeFT criteria in Ontario.
This projection does not include replacement volumes above those currently funded. While it
is reasonable to plan replacement volumes consistent with today’s practice (20%), the
appropriate replacement rate requires more conclusive long-term outcome data on primary ICD
use.
Risk Stratification in Primary Prevention
The recent primary prevention trials were designed to capture a broad patient population.
However the cost of this technology and the limited resources available requires a process to
better identify or risk stratify patients who would benefit the most from a prophylactic ICD.
16
December 2004
The Task Force discussed possible inclusion/exclusion criteria to assist referring physicians in
their clinical decision making related to prophylactic ICD insertion or a combined ICD/CRT
device based on the current available evidence.
Five primary prevention trials including MADIT-II, SCD-HeFT, DINAMIT, DEFINITE &
COMPANION were reviewed and considered in developing inclusion/exclusion criteria.
Factors that the Task Force considered from the literature included:
•
•
•
•
Two clinical factors that in combination, specify a population of patients that would derive
the most “benefit” from the prophylactic implantation of an ICD are:
• LVEF < 30%
• Presence of clinical heart failure symptoms (NYHA III) despite optimized heart failure
therapy.
Most patients enrolled in the studies were enrolled at least one year and in many cases,
many years after their “index event” (e.g. MI or heart failure presentation). MADIT II
reported no improvement in survival from prophylactic ICD implantation in the first 12
months after device implant (12). A MADIT II sub analysis reported that ICD survival
benefit increased from time of MI, with least survival benefit in patients with a recent MI
(<18 months) 34 . This information together with the results of the DINAMIT trial led the
task force to recommend that consideration for prophylactic ICD implantation be deferred
until 6 months after an “index event”. Allowing a longer “waiting period” will allow for
‘remodeling’ post MI, recovery of ‘stunned myocardium’ and optimization of
pharmacological therapy.
While the presence of a prolonged QRS duration (QRS >120 msec) has been shown to be
an independent predictor of long term mortality in patients with LV dysfunction and risk for
fatal dysrhythmias in the heart failure literature, the results reported by the SCD-HeFT
investigators has raised questions regarding its use as a predictor for the prophylactic ICD
population.
Trial data did not evaluate CRT in severe class IV heart failure patients who were
dependent on intravenous medications (inotropes). In this heart failure population CRT
therapy may be considered if their heart failure status can be improved to a NYHA Class
III.
The consensus of the Task Force is detailed in table III.
Economic Analysis:
Efficacy data regarding the primary prevention of sudden cardiac death and/or heart failure
from the clinical trials MADIT II and SCD-HeFT were combined with Ontario’s funding
formula to obtain Ontario-relevant cost-effectiveness ratios. The perspective of the payer - the
MOHLTC - was the perspective taken by the analysis and thus only direct medical costs were
considered in the analysis even though the indirect savings from avoiding morbidity is
potentially considerable.
Assumptions:
• The clinical outcomes in the different clinical trials can be attained in practice in Ontario
• The perspective of the payer--the amount that the Ontario Ministry of Health and Long
17
December 2004
Table III
Risk Stratification Criteria for Primary ICD & ICD/CRT Therapy
Inclusion Criteria:
ICD:
•
•
•
Ischemic or non-ischemic cardiomyopathy combined with:
• Left ventricular ejection fraction (LVEF) <30% measured by radionuclide
angiography (RNA) within 2-3 months of ICD implant, and
• Optimized medical therapy that includes betablockers, ACE inhibitors, ARBs,
statins and aspirin for at least 3-6 months prior to implant
Selected high risk patients with one of the following conditions may be considered:
•
Hypertrophic cardiomyopathy
•
Long QT syndrome
•
Arrhythmogenic right ventricular dysplasia (ARVD)
•
Congenital heart disease
•
Brugada’s syndrome
Patient must be able to give own consent
ICD/CRT:
Ischemic or non-ischemic cardiomyopathy
NYHA heart failure Class III-IV, despite optimal medical therapy as described above
QRS >120 msec
Ejection fraction <30% measured by radionuclide angiography (RNA) within 2-3
months of ICD implant or LVEF <35% and referred through a heart failure program.
•
•
•
•
Exclusion Criteria
• Cardiac disease with high probability of pump failure death where survival is not
expected to be altered by defibrillator therapy
• Patients who would benefit from major cardiac surgery (bypass or valve replacement)
or multi-vessel coronary angioplasty. These patients should be considered for
revascularization and if revascularized, should be reassessed 3-6 months post
procedure.
• Documented MI or a new diagnosis of heart failure within 6 months of implant.
These patients should be reassessed after medical optimization unless clear indication
for ICD therapy i.e. documented sustained VT.
• Presence of a systemic disease that would shorten life expectancy (< 2 years) or an
existing DNR order. (systemic disease i.e. metastatic cancer, cirrhosis)
• Presence of co-morbid illness, such as:
• Chronic renal failure requiring dialysis (primary prevention)
• Irreversible brain damage from pre-existing cerebral disease (i.e. debilitating
CVA/Dementia)
• Major psychiatric disease, (ETOH abuse, drug abuse)
• Chronic pulmonary disease requiring home oxygen for palliation
18
December 2004
•
•
•
•
•
Term Care directly reimburses hospitals for ICD implantation--captures a substantial
portion of the direct incremental medical costs incurred by “the health-care system” for
each case.
Incremental effectiveness of new technology (CRT/ICD) over conventional non-surgical
treatments will be at least as good as that for standard single/dual chamber ICDs for those
patients who have a clinical indication for CRT/ICD. (This is a reasonable assumption
given that the hazard ratio in the COMPANION trial had a hazard ratio of 0.74 - a 36%
drop in mortality vs. conventional treatment) (16). This is slightly more favorable than the
results obtained for the two ICD trials MADIT II and SCD-HEFT.
Added life years (LYs) and QALYs obtained for the primary prevention trials will be
proportional to those obtained in MADIT II for which such data is directly available. The
proportionality will be related to the hazard ratios obtained in the trials.
All subjects in the primary prevention of sudden cardiac death trials are expected to have
total health care costs, both before and after ICD insertion, above $30,700 per year, which
places them in the most expensive 1% of Ontarians. These health care expenditures are
due to the many comorbid conditions (diabetes, chronic obstructive pulmonary disease,
hypertension, etc) such patients often experience.
The distribution of health care costs among the population in 2004 is the same as that
obtained for the approximately 24,000 people randomly surveyed in the 1996 Ontario
Health Survey (OHS96).
Primary prevention of sudden cardiac death using ICDs is most effective in those people
with ejection fraction <=30%.
Existing ICD funding formula:
The current costing formula is based on data from fiscal year 1997 and incorporates device
cost, procedure cost, hospital inpatient stay of approximately 5 days and follow up care (22).
This formula does not account for the percentage of procedures performed as an outpatient,
since implantation of such devices was limited to the inpatient setting when such estimates
were made in 1999. Currently, approximately 33% of ICD procedures are performed on an
outpatient and most procedures can potentially be performed with at most, a one-night stay in
the hospital (5). Furthermore, the formula does not make any adjustment for the implantation of
a CRT/ICD device, which costs 20-30% more than a single/dual chamber ICD (33).
Potential Budget Impact of Primary Prevention ICD and ICD/CRT Therapy:
The annual budget impact was calculated for the population estimates suggested in the analysis
described above.
1. Ontario’s incident and prevalent heart failure population from population-based estimates
of left ventricular dysfunction from the published literature (9,575 incident population up to
86,400 prevalent patients).
If the province needed to absorb the ICD related implantation costs at today’s funding rate of
$32,500, the budget impact would be:
19
December 2004
•
•
a maximum of $311M if only the new heart failure patients each year were treated. The
incident cases of heart failure in Ontario has been estimated to be approximately 9,575.
a range of $770M to $2.4B if all estimated existing patients with heart failure in Ontario
were to receive this therapy.
Data to accurately identify prevalent heart failure is inadequate at this time, which explains the
wide variation in estimating budget impact. It is extremely unlikely that the maximum range is
realistic, or that resources could be justified or ever available to treat such a large population.
2. The relevant ‘symptomatic incident population’ was estimated by applying MADIT II and
SCD-HeFT criteria to a population of newly diagnosed hospitalized heart failure patients
(9,575). This methodology shortlisted 2,488 eligible incident patients.
Applying today’s $32,500 ICD therapy funding rate to the derived 2,488 ICD volumes
translates into a budget requirement of $81M. Excluding those devices that the task force
assumed are currently funded and implanted for primary prevention purposes today reduces the
net funding requirement to $71M annually.
It should be noted that if the funding formula was revised, the budget impact could be further
reduced.
Cost Effectiveness Analysis
Ontario based cost effectiveness estimates were calculated using the results and estimated
survival benefits associated with the MADIT II and SCD-HeFT trials.
MADIT II Results (4,26):
ICD vs. Placebo (overall) - Hazard Ratio =0.69 - 95% CI 95% (0.51:0.93) – p = 0.016
Difference in expected life years = 2.59 yrs (undiscounted)
Difference in expected life years = 1.85 yrs (discounted at 3%/yr)
Difference in expected QALY = 1.86 QALYs (undiscounted)
Difference in expected QALY = 1.33 QALYs (discounted at 3%/yr)
Ontario based CE estimated based on MADIT II population based on current funding formula
are: $17,568 per LY and $24,436 QALY
SCD-HeFT Results (6)
ICD vs. Placebo (overall) – Hazard Ration = 0.77 - 97.5% CI (0.62: 0.96) - p = 0.77
ICD vs. Placebo (NZ + Canada n=164) – Hazard Ratio = 0.37 - 97.5% CI (0.17: 0.82)
In calculating Ontario based CE based on the SCD-HeFT trial it was assumed that the LYs and
QALYs in SCD-HeFT are proportional to ratio of reduction in mortality between MADIT II
(31% reduction) and SCD-HeFT (23% reduction).
Overall Ontario Based CE results for SCD-HeFT population based on current funding formula
are $23,678/LY and $32,936/QALY
20
December 2004
Calculation of Uncertainty in CE: Meta-analysis and Application of Fieller’s Theorem.
Effects/Outcomes:
A meta-analysis of all the major primary prevention trials is summarized in table IV below for
the subsample of patients with ejection fraction < 0.30 35 .
Table IV
According to the meta-analysis performed, the hazard ratio for those with EF = <.30 varies
between 0.58 (42% reduction in mortality) and 0.86 (14% reduction in mortality).
Accordingly, the added LYs and QALYs associated with these hazard ratios, as determined in
comparisons with the MADIT II trial range between:
• .84 - 2.51 LYs
• .6 - 1.8 QALYs
Costs:
Relevant to costs, the major uncertainty involves inclusion of unrelated costs during the years
of increased life expectancy. Given the large number of comorbidities experienced by these
patients, these costs could be substantial. For the purpose of this analysis, unrelated heath care
costs that ranged from approximately $42,000 - $69,300 were calculated for those at risk for
SCD (refer to appendix VII for methodology). While there is substantial debate in the literature
about whether such costs should be included in cost-effectiveness ratios for prolonging
technologies like ICDs, the task force followed the recommendation of the Washington Panel
on Cost-Effectiveness. The panel recommended to include such costs in a sensitivity analysis
if they are large. 36 As a result, $32,500 (currently provided by the MOHLTC for ICD
insertion) was added to the range of unrelated costs to produce first year costs associated with
ICD insertion between $74,500 and $101,800.
Cost-Effectiveness:
Because Cost-effectiveness ratios are not distributed normally, standard statistical inference for
determining confidence intervals for such ratios should not be applied. The upper boundary of
21
December 2004
the 95% confidence interval for ICDs was determined by using a method developed by Wakker
and Klaasen utilizing Fieller’s theorem 37 38 (refer to appendix VII). The 95% confidence
intervals for ICDs have an upper boundary at approximately $121,000 / LY and $170,000 /
QALY.
Limitations of the Economic Analysis:
• Recent studies were conducted on data that is now a number of years old while the
technology has either improved greatly or wasn’t available for testing until recently (e.g.,
CRT-D).
• Although SCD-HeFT involved a maximum potential follow-up of 5 years (minimum of 2.5
years), there is some anecdotal evidence that differences in outcomes are likely to grow at
an increasing rate in the long term (i.e., > 5 years; therefore long-term CE ratios are likely
to be even more favorable than those reported above).
• SCD-HeFT has not yet been published in a peer-reviewed journal; therefore, the results
should be given less weight until they have been subject to this type of review.
• The cost-effectiveness of the CRT add-on to an ICD is unclear because the COMPANION
trial was not able to separate out the impact on mortality of the CRT component from the
ICD component (16)
Recommendations:
1. That the MOHLTC consider an annual ICD growth rate of 30% until a total of 3,350 ICD
devices are supported annually for primary and secondary purposes. This represents an
incremental increase of 2,181 ICD devices for primary prevention purposes annually over
the volume completed in 2003/04.
2. ICD/CRT therapy has been demonstrated to be beneficial to a select heart failure
population. While there is no evidence to identify an ideal volume, to ensure the
availability of this technology, the task force recommends that the MOHLTC and Ontario’s
advanced arrhythmia centres plan that 30% of their ICD volumes will be combined
ICD/CRT devices.
3. That Ontario arrhythmia centres that implant ICD and ICD/CRT devices for primary
prevention purposes should do so in consideration of the “risk stratification
inclusion/exclusion criteria” identified by the Task Force.
4. That the MOHLTC support an ICD database that is linked with an administrative database
such as that which exists at ICES for the purposes of monitoring utilization, patient
characteristics, uptake and long term outcomes. In addition, hospitals that are funded to
provide ICD services be expected to collect and report ICD data to a central database. The
data collected for the database should at a minimum encompass those data elements listed
on the referral form provided in appendix VIII. In addition, Ontario should explore the
opportunity of developing a relationship with CMS for the purpose of comparing outcome
data.
22
December 2004
5. That ICD data and new clinical evidence be reviewed annually to incorporate new
information about ICD effectiveness, and to refine risk stratification criteria.
6. That ICD and ICD/CRT devices be inserted at advanced arrhythmia centres with the
involvement of a cardiac electrophysiologist. Decisions to insert an ICD/CRT device
should include a heart failure specialist. Additionally, Ontario ICD centres must insert a
minimum of 100 devices annually. New ICD centres must insert a minimum of 50 ICD
devices annually and these services should be reviewed annually to assess their ongoing
viability until they insert 100 devices annually.
7. That the MOHLTC assess the necessary infrastructure (capital and human) to meet the
recommended projected demand for ICD and ICD/CRT technology.
8. That the MOHLTC revise the current ICD funding rate to reflect changes in practice,
expanded clinical criteria, replacement devices and follow up costs.
23
December 2004
Appendix I
Committee Structure and Terms of Reference:
The committee structure and terms of reference was developed through consultation between Dr. Keon and
ministry staff.
The task force was charged with identifying the target population that would benefit the most from the available
ICD resources.
The committee consisted of:
• Two researchers from the Institute for Clinical Evaluative Sciences (ICES)
• Two hospital administrators
• Two cardiac electrophysiologists
• One heart failure specialist
• Ministry staff
Term and Reporting Relationship:
The Task Force was to complete its mandate within 3-4 months of its initial meeting. The Task Force commenced
face to face meetings in May 2004 and met six times over a seven-month period. A work group was charged with
reviewing potential inclusion criteria to guide the ICES analysis met twice.
The Task Force reported to the Assistant Deputy Minster of Health, Acute Services Division.
Work Plan:
At the first meeting the Task Force revised the terms of reference to incorporate cardiac resynchronization therapy
(CRT). The task force also clarified their role in recommending budget implications of ICD technology. The
committee agreed that they could not advise the ministry or fulfill their objective without a review and discussion
of cost effectiveness and budget implications of ICD technology under the expanded clinical criteria.
The work plan developed by the Task Force at the first meeting included:
• Review previous reports complied on ICD technology that included:
• Literature review of ICD technology (November 2003) prepared by office of the Medical Advisory
Secretariat, Ministry of Health and Long Term Care.
• Centres of Medicare and Medicaid Services (CMS) 2003 decision memo.
• The Use of ICDs at the McGill University Health Centre 39
• American College Cardiology, American Heart Association & North American Society for Pacing and
Electrophysiology, 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia
Devices (ref)
• Review results of recent clinical trials or relevant reports, specifically:
• Sudden Cardiac Death in Heart Failure (SCD-HeFT)
• Defibrillators in Non-ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)
• Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)
• Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION)
• Review data from ICD centres, historical volumes, recommended volumes, current infrastructure and funding
methodology.
• Review of ICD policy and practice in other jurisdictions.
• Estimate Ontario’s eligible population under the MADIT II and SCD HeFT clinical criteria.
• Review previous reports on cost effectiveness of ICD therapy
• Develop final recommendations
ICD Task Force Terms of Reference:
Preamble:
ICD therapy was developed to prevent sudden cardiac death in individuals who had experienced life threatening
irregular heartbeats. The ministry has provided dedicated funding for ICD therapy for these high-risk patients
since 1988. A recent clinical trial (MADIT II) found that using ICD therapy in all patients with a prior heart attack
24
December 2004
and poor left ventricle function reduces all cause mortality. This criteria expanded the use of ICD therapy beyond
patients with a diagnosed life threatening arrhythmia. The uptake of MADIT II criteria by clinicians has resulted
in hospitals exceeding their dedicated funding available for ICD therapy.
Purpose:
The ICD Task Force will bring together clinical experts and health care administers to identify the target
population that would benefit the most from the available ICD therapy.
The recommendations presented to the ministry will represent the advice of the Task Force. The ministry is under
no obligations to endorse or implement the Task Force’s recommendations.
Objectives:
• The Task Force will review current recommendations on the use of ICD therapy for patients diagnosed to be
at high risk for sudden cardiac death (secondary prevention).
• The Task Force will review current evidence regarding the use of ICD therapy for primary prevention
• The Task Force will review current recommendations for the use of ICD therapy for primary prevention.
• The Task Force will examine the treatment options for those individuals that are not considered at high risk
for sudden cardiac death
• The Task Force will make recommendations for further evaluations/research to identify the patient population
at high risk of sudden cardiac death.
• The Task Force will examine the role of cardiac resynchronization therapy (CRT) as adjunct to ICD
therapy.
Membership:
Chair:
Dr. Wilbert Keon, Former CEO, The University of Ottawa Heart Institute
Committee Members
Dr. Doug Cameron, University Health Network
Dr. Stuart Connolly, Hamilton Health Sciences Corporation
Dr. Andreas Laupacis, Institute for Clinical Evaluative Sciences
Dr. Doug Lee, Institute for Clinical Evaluative Sciences
Dr. James MacLean, Markam Stouffville Hospital
Ms. Karen Meades, University of Ottawa Heart Institute
Mr. Leo Steven, Sunnybrook & Women’s College Health Sciences Centre
Dr. Stuart Smith, St. Mary’s General Hospital
Ministry Staff
Peter Biasucci, MOHLTC
*Dr. Eric Nauenberg, MOHLTC
Rosalind Tarrant, MOHLTC
*Special Consultant
Reporting Relationship:
The Task Force will report to the Assistant Deputy Minister, Acute Services Division.
Term:
The Task Force will conclude its mandate in 2-3 months.
Meeting Frequency & Location:
Four half day meetings over a 3 month period
Committee Support and Administration:
Priority Programs Unit will provide funding to support the work of the ICD Task Force including reimbursement
for travel expense claims for the Task Force members. The ministry will provide the Task Force with a copy of the
literature review completed by the ministry’s Health Technology Assessment Unit.
25
December 2004
Appendix II
Summary Primary Prevention ICD Trials
Study & Intervention
Inclusion Criteria
Outcome and
F/U
Mortality
MADIT (1996)
Moss et al.
ICD or conventional medical
therapy
Anti-arrhythmic drugs could
be used in either arm
Prospective RCT
N= 196 (95 Tx group)
Age 25-80yrs, MI > 3 weeks
prior to entry, documented
asymptotic unsustained VT
unrelated to MI, LVEF<35%
NYHA I-III inducible VT
non suppressible VT on
EPS, no indications for
CABG or PCI within 3
months
• All cause
mortality
• 5 year follow up
• average follow
up 27 months
•
CABG-Patch 1997 (Bigger
et al.)
ICD or usual medical
treatment.
Prospective RCT
N = 900 (Tx n=446 ICD and
454 control)
Randomized into two groups
above and below LVEF 20%
Patients allocated at time of
CABG to ICD or control
group (usual treatment)
Age< 80 yrs, scheduled for
CABG, LVEF < 36%,
abnormal or signal average
ECG
• Overall mortality
• average follow
up 32 + 16 months
MUSTT 1999
(Buxton AE)
N = 704 Randomized to
conservative treatment (no
antiarrhythmic therapy) or
EP guided therapy tiered
drug/drug or ICD/drug
Age<80 yrs, CAD, LVEF <
40%, nonsustained VT,
Inducible VT on EP study.
• Cardiac arrest or
arrhythmic death
• Secondary: total
mortality
• average followup 39 months
MADIT II 2002
(Moss et al)
N = 1232 RCT
ICD or conventional medical
treatment
Age > 21 yrs, MI > 1 month,
LEVF < 30%.
CAT 2003
(Bansch et al)
N = 104
Randomized to ICD or
conventional therapy
Age 18-70 yrs, IDCM < 9
months, LVEF < 30%
NYHA Class II or III
Comments
Mortality rate; 15.8% ICD
group and 38.6% medical
group
•
54% reduction in all cause
mortality with ICD
75% reduction in cardiac
•
mortality (12% VS 27%)
Hazard ratio 0.46 (95%CI 0.260.82) p=0.009
•
•
•
•
•
•
•
22.6% mortality in ICD group
(101 deaths) and 20.9% in
control group (95 deaths).
•
Hazard ratio 1.07 (95% CI 0.81 to
1.42)
• All cause
mortality
• average followup 20 months
•All cause
mortality at 1 yr
follow-up.
• mean follow up
5.5 yrs
•
Arrhythmic death/cardiac
arrest rate at 24 and 60 months
was 28% and 42% respectively
in intervention group and 18%
and 32% in conservative group
Relative risk = 0.80 (95% CI = 0.641.01)
Relative risk = 0.45 (95% CI =0.320.63 for patients with ICDs)
•
14.2% (105 deaths) in ICD
group vs. 19.8% (97 deaths) in
conventional treatment
•
31% reduction in the risk of
death at any interval among
patients in ICD group as
compared with patients in the
conventional therapy group).
Hazard ration = 0.69 (95% CI =
0.51- 0.93)
•
13 deaths in ICD group and 17
in control group
•
•
•
•
•
•
•
•
•
ƒ
•
•
•
•
Average EF 26%
60% of ICD group had shock discharge within 2 yrs.
NHS HTA identified methodological limitations that included: higher number of betablockers and digoxin use in the ICD group (No details of mathematical model to adjust for
this provided), selection bias may have occurred, patients selected randomization if they did
not respond to procainamide, large number of ICD patients still required antiarrhythmia
drugs, which may have interfered with ICD
19 therapy related adverse events in ICD group and 12 in conventional therapy group.
Average EF 27%
57% of defibrillator patients had shock discharge within 2 yrs.
An NHS HTA identified methodological limitations that included: surgeon had option of not
having the patients randomly assigned to a treatment arm if it was believed the ICD presented
a risk, CABG may have decreased the risk of SCD, inclusion criteria included ECG
abnormalities and non-induced VT. Inducible VT may be a better marker than ECG changes
of high risk of SCD.
Compared to MADIT and AVID, patients in CABG trial were a lower risk group.
Significantly more post operative infections occurred in the ICD group
Average EF 29%
The comparison between outcomes of those patients receiving ICD therapy compared with
antiarrhythmic therapy is not randomized and therefore can be regarded as an observational
study
The secondary end point did not reach statistical significance through the trend was toward
better performance in the intervention group.
All cause mortality at 60 months in the interventional arm was 24 vs. 55% in patients
receiving ICD compared with those who did not.
Average EF 23%
19% of ICD group had shock discharge within 2 yrs
Hospitalizations for new or worsened heart failure higher in the ICD group compared to
control group (19.9% vs. 14% respectively)
CMS analysis cited a number of methodological concerns with MADIT II. MADIT II design
stated that patients who already had a FDA indication (MADIT I) for an ICD were to be
excluded. Study population included patients who had a high likelihood of meeting MADIT I
criteria of inducibility. 583 MADIT II patients had EP testing prior to or during ICD
implant. Of these 36% were inducible, this subset would have had a large survival benefit
form an ICD. Unclear why there were no survival benefits were seen in the first 12 months.
Only 18.9% of the 710 patients who received an ICD received therapy from the devices
during course of the trial. In addition, absolute reduction in mortality (5.6%) was small
compared to MADIT I (23%).
Average EF 24%
Small sample size (investigators noted, if original number of 1,348 patients enrolled study
would still be underpowered)
Study stopped after 104 enrolled as all cause mortality at 1 year did not reach expected 30%
in control group
65% patients had NYHA Class II and 35% had NYHA Class III.
December 2004
Summary Primary Prevention ICD Trials (Cont’d)
Appendix II Cont’d
Study
Inclusion Criteria
Amiovert (2003)
(Strickbergre et al)
N = 103 Prospective
RCT
Randomized to ICD or
amiodarone
DINAMIT (2004)
N = 674 Randomized to
ICD or optimal medical
therapy
Age > 18yrs, non-Ischemic
dilated cardiomyopathy,
symptomatic non-sustained VT,
LVEF < 35%, NYHA I-III.
• Total mortality
• mean follow-up
2yrs
•
6 deaths in ICD group and 7 in
amiodarone group.
Age 18-80 yrs, MI 6-40 days,
LVEF < 35%, depressed heart
rate variability, elevated heart
rate.
• All cause mortality
• Secondary
arrhythmic death
• Mean follow up 30
months
• all cause mortality
based on minimum 2
yrs follow up
• Secondary
arrhythmic death
• Median follow up
was 45.5 months
•
62 deaths ICD groups 58 deaths in
medical therapy group
Secondary endpoint: 12 deaths ICD
group vs. 20 in medical group
• Death or
hospitalization from
any cause
• Secondary death
from any cause and
cardiac morbidity
•
SCD-HeFT (2004)
(Brady et al)
Prospective RCT
N = 2,521 Randomized
to placebo/optimal
medical therapy,
amiodarone/optimal
medical therapy or
ICD/optimal medical
therapy
Companion (2004)
(Bristow et al)
RCT N= 1,520
Randomized to optimal
medical therapy,
CRT/medical therapy or
ICD/CRT/medical
therapy
Age >18 yrs, ischemic and
nonischemic dilated
cardiomyopathy, heart failure >
3 months, LVEF < .35%,
NYHA II-III.
DEFINITE (2004)
(Kadish et al)
N = 458
Prospective RCT
ICD/standard medical
therapy vs. standard
medical therapy
Age 21-80 yrs, LVEF < 36%
non-ischemic dilated
cardiomyopathy, non-sustained
VT/PVCs, VT, VF
Age > 18 yrs, NYHF III or IV,
Ischemic or non-ischemic heart
failure, LVEF < .35% QRS >
120msec, PR > 150msec.
Outcome and F/U
• Death from any
cause
• Secondary, death
from arrhythmia
• Mean follow up 29
months
Mortality
•
•
Deaths 244 in placebo, 240 in
amiodarone and 182in ICD group.
Hazard ratio of ICD to control 0.77, 97.5%
CI =0.62 –0.96 p= 0.007).
Primary end-point 68% in medical
group and 56% in CRT and CRT/ICD
groups.
•
19-20% risk reduction in CRT and
CRT/ICD group. CRT/ICD group had
a 36% reduction in risk of death from
any cause
Hazard ratio =0.80 (95% CI 0.68-0.95
p = 0.10)
•
Secondary end point 77 deaths (25%)
medical group, 131 (21%) CRT group
and 105 (18%) deaths in ICD/CRT
group
Hazard ration =0.64, 95% CI 0.48-0.86,
p = 0.003)
•
28 deaths in ICD group vs. 40
standard therapy group
•
Mortality rate at 2 yrs 7.9% ICD
group vs. 14.1%.
Hazard ratio =0.65 (95% CI0.4-1.06
p=0.08)
Comments
•
•
•
•
•
Average EF 23%
Survival rate ant 1 and 3 year not statistical different (p=0.8)
No standard medical therapy group
Study stopped when prospective stopping rule futility was reached.
Small sample size
•
•
Mean LVEF 28%
Negative study
•
•
•
ƒ
Average EF 25%
Information limited to investigator’s reports. Trial has yet to be published
52% patients had ischemic cardiomyopathy
Trial used single lead shock only ICDs
CMS analysis noted that the overall absolute reduction in mortality was modest for
a trial with a median follow up of 45.5 months and trial was extended by 1 year
without a clear explanation,
ƒ
•
•
•
•
•
•
•
•
•
•
•
•
Means LVEF 21%
85% NYHA III
55% patients had Ischemic cardiomyopathy
Study design was 1:2:2 randomization weighted towards device therapy
265 of patients in medical group withdrew from study. Investigators modified
study to address the number of patients who withdrew
definition for any cause hospitalization changed after trial started
Mean follow up 11.9 months in medical group, 16.2 months in CRT group and
15.7 months in ICD/CRT group
Mean LVEF 21%
57% patients NYHA II
Single chamber ICDs used
17.9% patients received appropriate ICD shocks
21.4% patients received inappropriate ICD shocks, mainly for atrial fibrillation or
sinus tacycardia
NHS HTA = National Health Service Health Technology Assessment: CMS = Centers for Medicare & Medicaid Services: NYHA = New York Heart Association Functional Class: CABG = Coronary artery bypass graft: LVEF = left
ventricular ejection fraction: VT = ventricular tachycardia, VF = ventricular fibrillation: MI = Myocardial infarction: CAD = Coronary artery disease.
27
December 2004
Appendix III
Table A – ICD rate of growth since 1998/99
1998/99 1999/00 2000/01
2001/02
2002/03
ICD Actual Volumes
370
440
577
770
Annual % Growth
19%
31%
33%
No. of New ICDs
298
360
492
640
No. of Replacement
72
80
85
130
ICDs
% or Replacement of
19%
18%
15%
17%
Total
Hospital’s reports of actual volumes (Excludes pediatric volumes)
2003/04
888
15%
740
148
1154
30%
937
217
17%
19%
Average
26%
Figure I - Growth Projections - CCN's recommended volumes vs. 26%growth rate
3,500
3,000
2,500
Funded
volumes
Actual
2,000
CCNrecommended volumes
26% growth projection
1,500
1,000
500
1998/1999 1999/2000 2000/2001 2001/2002 2002/2003 2003/2004 2004/2005 2005/2006 2006/07
Fiscal Years
29
December 2004
Appendix IV
Table A Ontario Cardiac ICD Centres & Existing ICD Capacity
Advanced Arrhythmia Hospitals
2003/04
Immediate
Actual
Available
Volumes
Capacity
University Health Network, Toronto
**Maximum
Capacity
available in
2005/06
270
320
350
St. Michael’s Hospital, Toronto
161
Sunnybrook & Women’s College Health
Sciences Centre, Toronto
84
Kingston General Hospital, Kingston
87
London Health Sciences Centre, London
146
University of Ottawa Heart Institute,
160
Ottawa
Hamilton Health Sciences Corporation,
175
Hamilton
Southlake Regional Health Centre,
71
Newmarket
*Total
1154
*Excludes pediatric volumes
** Maximum capacity without capital expansion
250
250
225
260
200
220
300
260
230
220
230
230
150
200
1855
2040
31
December 2004
Appendix V
Literature Review:
The Task Force agreed that the literature review (9) on ICDs compiled by the Ministry’s
Health Technology Unit (HTU) provided a sufficiently detailed review of primary prevention
studies reported up to and including MADIT II. The Task Force focused its literature review
on data published since the HTU’s November 2003 release.
Sudden Cardiac Death in Heart Failure (SCD-HeFT) (6):
SCD-HeFT was a prospective randomized control trial that sought to determine if amiodarone
or a simple shock ICD reduced all cause mortality in patients with ischemic and non-ischemic
LVSD. Patients were randomized to three treatment arms: amiodarone therapy, ICD therapy
or a placebo. The study analyzed 2,521 patients diagnosed with ischemic or non-ischemic
dilated cardiomyopathy, class II or III heart failure, LVEF of <35% and no history of
sustained ventricular arrhythmias. The study was designed with a 90% power to detect 25%
reduction in mortality in either the amiodarone or ICD group compared with the placebo
group.
Patient baseline characteristics included: median age 60 years, mean LVEF 25%, average
duration of heart failure 24 months, 70% of the patients classified as NYHF class II and the
remainder class III, 52% of the patients had ischemic heart disease and the mean QRS
duration was 112ms. Patients were well medicated at baseline and the median duration of
follow up was 45.5 months (27)
Main findings:
• The mortality rate in the placebo group was 36.1% at 5 years or 7.2% per year.
• Simple shock reduced all cause mortality at 5 years by 23% in the ICD group compared
with the placebo.
• There was no effect observed for the amiodarone group compared with placebo
Subgroup analysis of mortality for ICD vs placebo showed that the relative benefits of ICD
therapy appeared greater in patients with NYHF Class II than in Class III (13,27).
Note: The results of the SCD-HeFT trial have not been published. Data pertaining to the trail
is limited to the early reports presented at the 2004 ACC meeting and published abstracts. .
Prophylactic Defibrillator Implantation in patients with non-ischemic dilated cardiomyopathy
(DEFINITE) Study (28).
DEFINITE was a prospective randomized study that sought to determine if an ICD will
reduce mortality in patients with non-ischemic mortality. Patients were randomized to
standard oral medical therapy for heart failure or medical therapy plus an ICD. The study
analyzed 458 patients with LVEF <36%, non-ischemic dilated cardiomyopathy, NYHA Class
I – III and the presence of ambient arrhythmias. The absence of clinically significant coronary
artery disease as the cause of cardiomyopathy was confirmed by coronary angiogram or a
negative stress imaging study. The primary end point was all cause mortality and a prespecified secondary end point was arrhythmic death. The study was designed to detect a 50%
difference in the rate of death due to any cause. Follow up was extended to include 68 deaths.
Patient baseline characteristics included: mean age 58 years, mean LVEF 21%, duration of
heart failure was 2.8 years, 57% had NYHA Class II and the remaining were split between
NYHA Class I and Class III, 22.9% had history of diabetes and the mean QRS was 115msec.
Of note was the duration of heart failure, which was longer in the standard group 3.3 years vs.
32
December 2004
2.4 years in the ICD (P=0.04). The mean follow up was 20 ±14.4 months. There was not
significant difference between the two groups with respect to drug treatment.
Main findings:
• The study did report reduced mortality in the ICD group versus the standard therapy group
(not statistically significance).
• The study did achieve statistical significance with respect to the secondary endpoint
arrhythmic death. There were 3 arrhythmic deaths in the ICD group compared to 14 in the
standard group.
The study reported that during follow up 41 patients received 91 appropriate ICD shocks and
49 received inappropriate ICD shocks for atrial fibrillation and sinus tachycardia.
Subset analysis revealed that an ICD significantly reduced the risk of death among male
patients with NYHF Class III. Interpretation of the subset analysis results reported between
class II and III heart failure patients in SCD-HeFT and DEFINITE require further evaluation
when the detailed results are published.
The DEFINITE investigators concluded that based on their study the routine use of an ICD
cannot be recommended for all patients with non-ischemic cardiomyopathy and severe LVEF.
Based on subset analysis it should be considered on case by case basis.
Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) (11)
DINAMIT was a randomized trial that sought to determine if ICD therapy will reduce
mortality in patients with recent myocardial infarction (within 6 - 40 days) who are at a high
risk of death. Patients were randomized to optimal medical therapy or optimal medical
therapy plus an ICD. The study analyzed 674 patients, age 18 –80 years, with an acute MI
(within 6-40 days), LVEF <35% and depressed heart rate variability and elevated heart rate.
The primary end point was all cause mortality. Secondary endpoint was death due to cardiac
arrhythmia. Mean duration of follow up was 30 months (27) .
Due to a lower than expected mortality rate the number of patients was increased to 674
during the course of the study.
Patient baseline characteristics included: mean age 62 years, mean LVEF 28%, 72% had an
anterior infarction and 52% had heart failure with the index MI. Patients in both groups
received optimal medial therapy.
Main findings:
• ICD therapy did not decrease all cause mortality when used early in high risk post MI
patients
• ICD therapy did significantly reduce arrhythmic death in the ICD group but this was off
set by an increase in non-arrhythmic death in these patients (27).
Subset analysis has shown that following ICD therapy, mortality from non-arrhythmic death
is high.
Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION)
(16).
The companion study was a randomized study that sought to determine whether the use of
biventricular stimulation with a pacemaker (cardiac resynchronization therapy) with or
33
December 2004
without a cardiac defibrillator would reduce the risk of death and hospitalization in patients
with advanced heart failure.
Patients were randomized on a 1:2:2 ratio to three treatment arms, optimal medical therapy,
optimal medical therapy with CRT or optimal medical therapy with CRT/ICD. The study
analyzed 1,520 patients with LVEF <35%, NYHF Class III or IV resulting from ischemic or
non-ischemic cardiomyopathy, QRS > 120msec and a PR interval > 150msec, sinus rhythm,
no clinical indication for a pacemaker or an ICD and no heart failure hospitalization for the
preceding 12 months. The primary end point was composite of death or hospitalization from
any cause. Death from any cause was a secondary endpoint. The study was designed to
deduct a reduction of 25% in the primary end point. As the study was not blinded a
substantial (and unanticipated) number of patients withdrew from the medical therapy group
when the devices became available commercially, in order to receive a device. This was
particular in those patients who became eligible under the MADIT II criteria. Measures were
implemented to mitigate the impact of patient withdrawal on end-point analysis.
On the recommendation of the Independent Date Safety and Monitoring Board the study was
terminated early on November 2002.
Main findings:
• 68% of the medication only group died or were hospitalized in the follow up period vs.
56% in each of the other two treatment arms. This represented a 19% reduction in the
primary end point (death or hospitalization) for the CRT group over the standard medical
treatment group and a 20% reduction in the CRT/ICD group over the standard medical
group.
• the risk of combined end point of death from or hospitalization for heart failure was
reduced by 34% in the CRT group and 40% in the CRT/ICD group.
• the risk of secondary end point (reduction of death from any cause) was reduced 36% was
reported in the CRT/ICD group and 24% in the CRT group over medical therapy alone.
Subset analysis showed that CRT/ICD showed a 27% reduction in all cause mortality over
medical therapy in patients with ischemic cardiomyopathy (similar to MADIT II results) and a
50% reduction in the subgroup with non ischemic cardiomyopathy.
34
December 2004
Appendix VI
Estimating Need for ICD based on MADIT II and SCD-HeFT Criteria:
Approach 1. Estimation of need for implantable defibrillators based on the communitybased prevalence of left ventricular systolic dysfunction.
In this set of initial analyses, the published literature was searched for the relative prevalence
of LVSD in the community. A number of reports of left ventricular systolic function among
community-based heart failure patients were identified. Senni et al published the experience
from heart failure patients in Olmstead County, Minnesota, and reported that 57% of patients
had low ejection fraction 40 . Redfield et al conducted a cross-sectional study of 2,042
randomly-selected community-based individuals and found that in patients with heart failure,
56% had low ejection fraction (30). Vasan et al studied patients with heart failure from the
Framingham Heart Study and found that 49% had low ejection fraction 41 . Masoudi et al
published the largest study (n = 19,710) of community-based heart failure patients with data
on left ventricular systolic function 42 . In this study of individuals ≥ 65 years of age, the
authors found that 66% of patients had impaired systolic function defined as a left ventricular
ejection fraction ≤ 50% (42). Krumholz et al conducted a retrospective evaluation of 1,623
patients admitted with heart failure in nine acute care hospitals in Connecticut, and found that
48% of individuals with ejection fraction assessed had reduced systolic function 43 . Philbin et
al also retrospectively identified 2,906 patients admitted to acute care hospitals for heart
failure, and found that 57% had reduced ejection fraction 44 . Definitions for reduced ejection
fraction varied slightly; in the first 4 studies the threshold was ≤ 50% and the latter 2 studies
employed a threshold of ≤ 40%. However, despite these differences, the proportions of heart
failure patients with low ejection fraction were consistently similar. The weighted average of
all five studies suggested that 53% of heart failure patients have low ejection fraction.
Heart failure patients who were admitted to an acute care hospital in Ontario were identified
using the Canadian Institute for Health Information discharge abstract database using the
primary diagnosis code of ICD-9 428. The numbers of heart failure patients who were
hospitalized in Ontario each year from fiscal year 1997/98 to 2001/02 are shown in Table 1.
TABLE 1. Ontario numbers of hospitalized patients identified from the CIHI discharge
abstract database and those seeking medical care from the OHIP database. Note that
hospitalized HF patients are a prevalent cohort. Individuals who seek care for heart failure
are included only if they have two or more OHIP claims for diagnosis code 428.
Year
1997/98
1998/99
1999/00
2000/01
# of Patients hospitalized
(CIHI)
18,403
17,861
17,464
17,544
17,029
# of Patients w/ ≥ 2 OHIP
claims 428
61,710
61,206
61,505
61,946
60,754
Although there appears to be a marginal decline in total hospitalizations, the number of
hospitalized patients with heart failure were largely consistent from year to year. There were
approximately 17,000 admissions for heart failure in 2001/02. Prior studies have
demonstrated that a large proportion of patients admitted with heart failure have had prior
hospitalizations. Therefore, when admissions in the year 2001/02 were restricted to new
35
December 2004
hospitalizations by examining all individuals with prior heart failure admissions in the
preceding 5 years, we identified 9,575 unique, newly-admitted patients with heart failure.
We anticipated that the numbers of heart failure patients in the community would be higher
that those identified in the hospital-based setting. To estimate the potential degree of
underestimation, we examined physician fee reimbursement data in the OHIP database. To
increase specificity of the identification of heart failure patients, we required two temporally
distinct diagnoses of heart failure (ICD-9 428) recorded as the diagnosis to be counted as a
heart failure case.
The results are shown in Table 1, and based on this criterion, there are over 60,000 unique
patients who seek medical attention for heart failure. Again, there was consistency in
numbers from year to year.
The numbers above are consistent with heart failure prevalence estimates from a recent survey
of Canadians conducted by Statistics Canada (31). In this study, called the Canadian
Community Health Survey, randomly identified individuals were asked to give a self-reported
history of the diagnosis of heart failure. A summary of the data for self-reported heart failure
is shown in Table 2. The prevalence of heart failure in participants ≥ 20 years of age was
1.17%. Extrapolating to Ontario using population projections from Statistics Canada, the
number of adults in Ontario is 8,640,831 and the number of patients with self-reported heart
failure in Ontario would be 101,098 persons. Assuming that approximately half of all persons
with heart failure have LVSD, the estimated number of patients with LVSD in Ontario would
be 50,549 persons.
TABLE 2. Self-reported prevalence of congestive heart failure from the Canadian
Community Health Survey, stratified by age group (31).
Age
12 to 19
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 79
80 +
Total
# with HF reported
2,100
4,226
7,001
18,426
38,029
52,396
85,186
56,696
264,060
Denominator
3,318,117
4,118,589
4,746,631
5,077,402
3,637,171
2,396,167
1,744,169
749,088
25,787,334
% Prevalence
0.06
0.1
0.15
0.36
1.05
2.19
4.88
7.57
1.02
In contrast to the studies described above, where there were variable thresholds of left
ventricular ejection fraction, Redfield et al identified the population-based prevalence of
varying cutoffs for left ventricular ejection fraction (30). In this study, individuals from the
population were randomly-selected for detailed echocardiographic assessment and
proportional rates were identified by left ventricular ejection fraction threshold (reproduced in
Figure 1). Approximately 2% of persons in the community had a left ventricular ejection
fraction of 40% or less. With lower cutoff values of left ventricular ejection fraction, the
percentage of individuals in the population was progressively less: approximately 1% of
persons had a left ventricular ejection fraction ≤ 35% and 0.5% had a left ventricular ejection
fraction ≤ 30%. Translating these findings to Ontario, we would anticipate that approximately
43,204, 86,408, and 172,817 persons would have left ventricular ejection fractions ≤ 30%, ≤
35%, and ≤ 40%, respectively.
36
December 2004
The methods described in the above approximations illustrate the potential magnitude of heart
failure cases in community-based populations. Estimates of the prevalence of LVSD were
obtained from the literature. However, the population-based prevalence estimates may not
reflect the frequency of the condition in patients that would normally seek medical care.
Specifically, screening programs for the presence of left ventricular dysfunction are not in
effect, and therefore, the population-based estimates of LVSD described above may not
reflect the numbers of identified cases of the condition in
Figure 1. Population-based prevalence of left ventricular systolic dysfunction.
Reproduced from Redfield et al (30)
37
December 2004
Ontario. In Ontario, access to a diagnostic test to assess left ventricular ejection fraction
would initially be required. The second approach (described in the next section), examined
the prevalence of LVSD in patients who underwent diagnostic echocardiographic testing.
Ontario-specific analysis utilized the findings of Alter et al, who examined a convenience
sample of 1000 persons undergoing echocardiographic evaluation at a community-based
laboratory (32). In this study, the prevalence of a left ventricular ejection fraction ≤ 35% was
8.3% of all individuals undergoing echocardiography. Since this prevalence rate reflects
individuals who have undergone echocardiographic assessment, if the prevalence estimate of
LVSD is projected to individuals who have undergone echocardiography, there would be a
total of 23,794 patients with LVSD in a cross-sectional sample of year the year 2001.
In this approach, estimates from the literature, surveys, and a sample of patients undergoing
echocardiography at a community-based laboratory were utilized to provide estimates of the
potential pool of patients who might be considered candidates for implantable defibrillators
based primarily on left ventricular ejection fraction. Although ejection fraction criteria alone
reduces the potential numbers of patients who may need defibrillators, due to the nature of the
above data, the exclusion criteria employed in the randomized controlled trials have not been
instituted. Specific exclusion criteria had been employed by the investigators of the MADIT
II and SCD-HEFT trial (4) (6). The exclusion criteria were also employed by CMS in their
statement regarding the indications and funding of implantable defibrillators (12). These
exclusion and inclusion criteria were explored and in Approach 2 to further refine the
estimates of the potential need for implantable defibrillators in Ontario.
Approach 2. Identification of potential need for implantable defibrillators based on
hospitalization cohort.
This method employed data of patients hospitalized with acute myocardial infarction and
heart failure to an acute care hospital in Ontario. Clinical data collected as part of the
Enhanced Feedback For Effective Cardiac Treatment (EFFECT) study were utilized since
there is greater clinical detail in this dataset (29). The EFFECT study was funded by the
Canadian Institutes of Health Research and the Heart and Stroke Foundation, and consists of
patients with acute myocardial infarction (EFFECT-MI) and heart failure (EFFECT-HF). The
inclusion and exclusion criteria for implantable defibrillators in MADIT-II and SCD-HEFT
(4,6) were applied to heart failure patients identified in EFFECT-MI and EFFECT-HF, where
applicable. To determine the incident cases of patients that may require defibrillators in
Ontario, we projected the ratios of candidates from EFFECT to heart failure patients in
Ontario.
Newly-admitted heart failure patients were identified from the Canadian Institute for Health
Information discharge abstract database using a washout period of 5 years. Therefore, any
patient who had been admitted to hospital with a diagnosis of heart failure within 5 years of
the index admission was excluded from the analysis. Using this approach, in Ontario, in the
year 2001/02, there were 9,575 patients admitted with heart failure. The numbers of newlyadmitted heart failure patients were consistent from year to year. Numbers of patients
admitted with acute myocardial infarction were also identified from the Canadian Institute for
Health Information discharge abstract database. As in prior studies that have examined
population-based acute myocardial infarction patients, we employed an examination period of
1 year prior to the index admission to avoid double-counting of events. Using this criterion,
there were 17,294 patients admitted with acute myocardial infarction in Ontario.
The criteria for the MADIT-II study as applied to acute myocardial infarction patients
(EFFECT-MI) in Ontario are shown in Table 3. The sample of patients with heart failure
38
December 2004
could also be used to estimate the numbers of implantable defibrillators needed to fulfill
MADIT-II criteria, and therefore provides another estimate. Since the EFFECT-MI and
EFFECT-HF datasets have independently-collected variables, the criteria for MADIT-II are
slightly different and are shown in Table 4 (4). The inclusion and exclusion criteria for the
SCD-HEFT trial were extracted from the investigators’ website documenting the presentation
of preliminary results at the Scientific Sessions of the American Heart Association (6), since
this study has not yet been published as of the writing date of this document. A similar set of
inclusion and exclusion criteria were extracted from the prior CMS document on implantable
defibrillators and applied to SCD-HEFT as shown in Table 5. The inclusion and exclusion
criteria were reviewed for consensus by the Defibrillator Taskforce.
One major criterion for the defibrillator trials was the presence of left ventricular systolic
dysfunction. A large proportion (approximately 50%) of patients admitted to hospitals in
Ontario did not undergo an assessment of left ventricular systolic function by either
echocardiography, radionuclide angiography, or cardiac catheterization. Two methods were
employed to deal with the lack of data on LVEF. In the liberal estimate, we assumed that the
proportion of patients with LVSD who had their LVEF assessed would be similar to those
patients who did not undergo assessment of left ventricular function. In the conservative
estimate, we assumed that patients who did not undergo assessment of left ventricular
function did not have LVSD.
Another major criterion for MADIT-II proposed by CMS was the presence of wide QRS
(defined as a QRS duration ≥ 120 milliseconds) (12). In EFFECT, the QRS duration was not
collected. However, the presence of (right or left) bundle branch block was collected and
used as a surrogate for wide QRS. We limited the numbers of patients who would be eligible
for implantable defibrillators by excluding patients who did not survive for 90 days after
hospital admission. A sensitivity analysis was conducted by excluding patients who did not
survive 30 days after hospital admission (rather than 90 days post-admission). However, the
numbers for 90-day survivors are reported as the primary results since the overall impact on
the total numbers of defibrillators required was small.
39
December 2004
TABLE 3. MADIT-2 PATIENTS IN
ONTARIO (USING EFFECT AMI)
1.
2.
3.
4.
5.
6.
7.
8.
EF ≤ 30%
Exclude patients with cardiogenic
shock
• Complications = Yes;
• Cardiogenic shock = Yes
Exclude patients with CVA or CNS
hemorrhage:
• CT Scan = Yes; Outcome =
Moderate, Severe disability, or
Death OR
• Hemorrhage = Yes; Site = CNS
Exclude patients who are DNR:
• DNR = Yes
Exclude patients unable to consent:
• Admitted from Nursing Home or
LTC
• Discharged to LTC or CC Care
Exclude patients with severe limiting
comorbidities:
• Aortic stenosis (moderate or
severe)
• Cancer metastatic
• CNS disease
• Dementia / Alzheimer’s
• Liver disease (chronic)
• Renal disease (dialysis
dependent)
• Complications = ARF with
dialysis
Exclude if no Bundle Branch Block
or transient BBB only
• BBB = No on ECG 1A
• BBB = No on ECG 1B
• BBB = No on ECG 2
Exclude patients who do not survive:
1. 30 days
2. 60 days
3. 90 days
TABLE 4. MADIT-2 PATIENTS IN
ONTARIO (USING EFFECT CHF)
1.
2.
3.
4.
5.
6.
7.
8.
9.
LVEF ≤ 30%
Exclude patients who have no prior
MI:
• Etiology = Cardiomyopathy
AND
• Cardiomyopathy type NOT
CAD
Include patients with prior
documented MI:
• Cardiac and vascular disease:
Previous MI = Yes
Exclude patients unable to consent:
• Lives = Institutionalized
• Admitted from = LTC/NH
• Discharge to LTC or CC Care
• Comatose on arrival
• Dementia / Alzheimer’s = Yes
Exclude patients with cardiac
arrest (secondary prevention):
• Arrest pre-arrival = Yes
• Complications: Cardiac arrest
= Yes
Exclude significant comorbidities
or CV disease:
• CVA = Yes
• Cancer = Yes
• Cirrhosis = Yes
• Frailty = Yes
• HIV/AIDS = Yes
• Renal dialysis = Yes
• ECHO: Aortic stenosis = Yes
AND Severity = Critical
• ECHO: Aortic regurgitation =
Yes AND Severity = Severe
• ECHO: Constriction = Yes
• Complications: CVA = Yes
• Complications: Renal failure
= Yes
• Drugs: Home Oxygen = Yes
Exclude if DNR:
• Outcomes DNR = Yes or
Comfort Measures = Yes
Exclude if BBB = No
Exclude pts who did not survive:
1. 30 days
2. 60 days
3. 90 days
TABLE 5. SCD-HeFT ANALYSIS
(USING EFFECT CHF)
1.
2.
3.
4.
5.
6.
LVEF < 35%
Exclude patients unable to consent:
• Lives = Institutionalized
• Admitted from = LTC/NH
• Discharge to LTC or CC Care
• Comatose on arrival
• Dementia / Alzheimer’s = Yes
• Exclude patients with cardiac
arrest (secondary prevention):
• Arrest pre-arrival = Yes
• Complications: Cardiac arrest =
Yes
Exclude significant comorbidities or
CV disease:
• CVA = Yes
• Cancer = Yes
• Cirrhosis = Yes
• Frailty = Yes
• HIV/AIDS = Yes
• Renal dialysis = Yes
• ECHO: Aortic stenosis = Yes
AND Severity = Critical
• ECHO: Aortic regurgitation =
Yes AND Severity = Severe
• ECHO: Constriction = Yes
• Complications: CVA = Yes
• Complications: Renal failure =
Yes
• Drugs: Home Oxygen = Yes
Exclude if DNR:
• Outcomes DNR = Yes OR
Comfort Measures = Yes
Exclude if BBB = No
Exclude pts who did not survive:
• 30 days
• 60 days
• 90 days
40
December 2004
The number of patients who are potential candidates for implantable cardioverter
defibrillators after excluding patients who have exclusion criteria, using an acute myocardial
infarction cohort are shown in table 6
TABLE 6.
Estimating potential number of MADIT II ICD patients from EFFECT AMI.
Ejection Fraction
BBB Exclusion (Y/N)
Number of Patients
Criterion
Surviving 90 Days Post-MI
Eligible for ICD
Liberal
No
2011
Conservative
No
866
Liberal
Yes
1465
Conservative
Yes
631
Applying stringent criteria for implantation of the ICD would require that 631 defibrillators
would be required to meet MADIT II criteria in Ontario. The application of more liberal
criteria would necessitate that 2011 defibrillator implants would be required.
The estimates above employ a cohort of patients admitted with acute myocardial infarction to
an acute care hospital. However, there are several potential reasons why a cohort of patients
with heart failure would be more appropriate for the purposes of future need for implanted
devices.
A fundamental reason is that the presence of LVSD in the post-MI stage may not reflect left
ventricular function at a later point in time. The reasons for this include myocardial stunning,
compensatory contractile changes occurring in non-infarcted myocardium, and effect of
pharmacotherapies that may improve left ventricular systolic performance.
Another reason for using a heart failure cohort as a starting point for estimation was the
observation among electrophysiologists that the majority of referrals for implantable devices
in patients with prior myocardial infarction was from heart failure specialist physicians.
Finally, the evidence for benefit of ICDs in the early post-myocardial infarction phase is not
compelling. The DINAMIT trial, which compared ICD versus conventional therapy in
patients post-myocardial infarction showed a tendency toward a reduction of arrhythmic death
but no impact on overall mortality (11).
For the above reasons, the MADIT II analyses were also performed using a heart failure
cohort and the results are shown in Table 7.
TABLE 7.
Estimation of potential number of MADIT II ICD patients from EFFECT HF.
Ejection Fraction
BBB Exclusion (Y/N)
Number of Patients
Criterion
Surviving 90 Days Post-MI
Eligible for ICD
Liberal
No
892
Conservative
No
416
Liberal
Yes
594
Conservative
Yes
277
41
December 2004
Using the most stringent criteria, among a heart failure cohort, 277 implantable defibrillators
would be required to meet MADIT II criteria in Ontario. This estimate is predicated on the
exclusion of potential candidates based on the presence of bundle branch block (BBB) on
electrocardiography. Although the presence of BBB is in a subset of wide QRS
morphologies, it was recognized that the two ECG findings are not synonymous.
Furthermore, the BBB restriction initially suggested by regulators at CMS has been a subject
of intense scrutiny and criticism because it is based on a post-hoc analysis of randomized trial
data. For these reasons, extreme caution was warranted in using the BBB exclusion criterion,
and the task force favoured not using the BBB criterion to restrict access to ICDs.
Without regard to the presence of BBB, and using the liberal EF criterion for MADIT II
indications, 892 defibrillators would be required in Ontario. Applying conservative criteria
for LVEF assessment, would decrease the number of ICDs required to 416 defibrillators.
It was recognized by the task force that access to diagnostic tests that enable assessment of
left ventricular function may be limited depending on geographic location. In fact, a recent
survey of hospitals conducted by ICES investigators found that a number of hospitals in
Ontario did not have access to echocardiography. Therefore, the more liberal ejection fraction
criterion was felt to be most appropriate, and an estimated 892 defibrillators would be
required to meet MADIT II criteria in Ontario. The estimated numbers of defibrillators
required to meet SCD-HeFT criteria are shown in Table 8.
TABLE 8.
Estimation of potential number of SCD-HeFT ICD patients from EFFECT HF.
Ejection Fraction
BBB Exclusion (Y/N)
Number of Patients
Criterion
Surviving 90 Days Post-MI
Eligible for ICD
Liberal
No
2521
Conservative
No
1176
Liberal
Yes
1775
Conservative
Yes
828
The numbers are larger than those in Tables 6 and 7 because of the broad inclusion criteria in
this study. Using the liberal criterion for ejection fraction, it was estimated that 2521
defibrillators would be required to meet SCD-HeFT criteria in Ontario. The conservative
ejection fraction estimate is shown in the table, but was not favoured for the reasons described
above. In Table 8, two additional estimates are shown for restriction based on the presence of
BBB. However, it is emphasized that the presence of BBB was not an inclusion or exclusion
criterion for the SCD-HeFT trial. Additionally, the presence of BBB has not been shown in
subgroup analysis to be a significant predictor of defibrillator efficacy.
Overlap between MADIT-2 and SCD-HeFT.
The estimates shown in Tables 7 and 8 used two sets of criteria that have some degree of
overlap, since both estimates are derived from the same cohort of heart failure patients. Given
the broad inclusion criteria in SCD-HeFT, specifically, the inclusion of patients with LVSD
and prior myocardial infarction, a proportion of the estimates in Table 8 would likely overlap
with MADIT II estimates. For example, a given patient could meet both MADIT-II and SCDHeFT criteria, based on the presence of ischemic left ventricular dysfunction.
42
December 2004
Therefore, the proportion of SCD-HeFT patients who did not also meet MADIT-2 criteria
were identified to avoid the potential for double-counting. The proportion of patients overall
who met only SCD-HeFT criteria was 71.6%. Therefore, the liberal SCD-HeFT estimate
(Table 8, row 1) of 2521 ICDs would be reduced by 28.4% to identify those who meet SCDHeFT criteria exclusively. The proportion of heart failure patients with LVSD who met only
SCD-HeFT criteria was 63.3%. The above estimates of overlap are irrespective of the
presence of BBB. Among patients with BBB, the degrees of overlap were similar. Overall,
73.4% of patients with BBB met exclusively SCD-HeFT criteria and among patients with
LVSD, 69.5% of patients met SCD-HeFT criteria only.
43
December 2004
Appendix VII
Determination of Unrelated Health Care Cost
The major uncertainly surrounding costs is the inclusion of unrelated costs during the years of
increased life expectancy. Given the large number of cormorbidities experienced by these patients,
these costs are expected to be substantial. It is assumed that the medical expenditures of patient’s
eligible of prophylactic ICD therapy will be in the most expensive 1% of the population. Using the
distribution of health expenditures 45 from those who participated in the 1996 Ontario Health survey,
we superimposed on this distribution the most recent CIHI provincial government expenditure
estimates for Ontario ($29.146 billion) 46 and population estimates (12.3 million for 2003) 47 . As a
result of this process, we were able to obtain health care expenditure estimates for the most expensive
1% of Ontarians which ranged from approximately $30,700 to over $200,000 per year.
To obtain 95% confidence intervals for these unrelated costs, random samples of 10,000 (the
approximate size of the incident population with heart failure) were repeatedly sampled from the
population representing the most expensive 1% (approximately 1% x 12.3 million = 123,000). This
bootstrap technique (sampling with replacement) was performed with 1000 replications producing an
average of $56,674 per year with a 95% confidence interval between $42,032 and $69,325. In other
words, unrelated health care costs for those at risk for sudden cardiac death range from approximately
$42,000 to $69,300 per year.
Cost Effectiveness:
Because Cost-effectiveness ratios are not distributed normally, standard statistical inference for
determining confidence intervals for such ratios should not be applied. Instead we apply a method for
determining such intervals developed by Wakker and Klaasen utilizing Fieller’s theorem (37, 38).
The first step is to take the upper boundary of the confidence interval for costs ($101,800) and then to
take the lower boundary of the confidence interval for Effects / Outcomes (0.84 LYs, .60 QALYs).
Wakker and Klaasen suggest that taking these two figures and dividing them to produce a costeffectiveness ratio will provide a conservative estimate of the upper boundary of a 95% confidence
interval for the cost-effectiveness of the intervention. As a result, the 95% confidence intervals for
ICDs have an upper boundary at approximately $121,000 / LY and $170,000 / QALY.
This information is summarized in the table below.
Summary: Upper Boundary for 95% confidence intervals for ICD Implantation
$180,000
$160,000
$140,000
$/L
Y $120,000
or
$/Q $100,000
AL
$80,000
Y
$60,000
$40,000
$20,000
$0
CE ($ / LY)
CE ($ / QALY)
44
December 2004
Appendix VIII
ICD – ICD/CRT REFERRAL FORM
Reason for Referral:
Secondary
Primary - CAD LVEF<30% Non-CAD LVEF
Other:
<30%
Replacement:
Date of Referral: (M/D/Y)_________________________
Patient Demographics
Urgency Rating:
Urgent (while still in hospital)
Patient’s Present Location:
Home
Hospital
ICD
Ward Name
Translator Needed:
Yes
No Language:
Referring MD:
ICD Centre Requested
1st available
Elective
Brief History:
NYHA Heart Failure Class:
I
II
III
IV
LV Function:
RNA
Yes, when (m/d/y)
No
LVEF <30%
Yes
No
yes, when (m/d/y)________
No
LVEF:
%
Previous MI
Previous CABG:
Previous PCI:
yes, when (m/d/y) _______
No
yes, when (m/d/y) ________
No
New heart failure diagnosis within last 6 months:
Yes, when (m/d/y)
No
Cath:
Yes, when (m/d/y) ________
Cath scheduled:
No
yes, when (m/d/y)_________
No
QRS width: _______________(Fax ECG)
Atrial Fib
Yes
No
Existing pacemaker
No
Yes
Creatinine:______________Urea___________
Pending
Yes
Not done
Weight :
kg
Medication History:
Anticoagulation History: Coumadin Yes
Anticoagulation Indication:
A fib
LV Function Previous Stroke
ACE: Inhibitor: Yes
No
Not tolerated
ARB:
Yes
No Not tolerated
Beta blockers
Yes
No
Not tolerated
ASA,
Yes
No
Not tolerated
Statins
Yes
No
Not tolerated
Other lipid lowering agent:______________
No
Other
Mandatory Field
ICD Inclusion Criteria:
Inclusion:
Ischemic or non-ischemic cardiomyopathy, combined with
LVEF <30% measured by RNA within 2-3 months of ICD
•
implant, and
Optimized medical therapy as noted on reverse side for at least
•
3-6 months
Referred for one of the following conditions:
Hypertrophic cardiomyopathy
•
Long QT syndrome
•
Arrhythmogenic right ventricular dysplasia
•
Congenital heart disease
•
Brugadas Syndrome
•
Patient able to give own consent:
ICD/CRT Inclusion Criteria:
Ischemic or dilated cardiomyopathy
NYHA Heart Failure Classification III- IV
QRS >120 msec
LVEF <30% measured by RNA within 2-3 months of ICD
implant LVEF <35% referred through heart failure program
Exclusion criteria for ICD or ICD/CRT
Cardiac disease with high probability of pump failure death where
survival is not expected to be altered by defibrillator therapy
Patients who would benefit from cardiac surgery (bypass or valve
replacement) or multi-vessel coronary angioplasty. These patients
should be considered for revascularization and if revascularized,
should be reassessed 3-6 months post procedure.
Documented MI or a new diagnosis of heart failure within 6
months of implant (these patients should be reassessed after
medical optimization unless clear indication for ICD therapy i.e.
documented sustained VT).
Presence of a systemic disease that would shorten life expectancy
(<2 yrs) or an existing DNR order.
Presence of co-morbid illness
Chronic renal failure requiring dialysis (primary prevention)
•
Irreversible brain damage from pre-existing cerebral disease
•
(i.e. debilitating CVA/Dementia)
Major psychiatric disease, (ETOH abuse, drug abuse)
•
Chronic pulmonary disease requiring home oxygen for
•
palliation
45
December 2004
Definitions
Primary Prevention:
Implantation of an ICD for prophylactic purposes in individuals who have been identified as
high risk for SCD but have not experienced a life threatening arrhythmia, survived SCD or in
individuals who are have inducible ventricular arrhythmias at electrophysiology studies.
Secondary Prevention:
Implantation of an ICD for secondary prevention purposes in individuals who have survived
SCD or who have demonstrated life threatening arrhythmias.
Ejection Fraction Measurement
Left Ventricular Ejection Fraction (LVEF) must be measured by radionuclide
angiocardiography (RNA) within 2-3 months of implant date
Heart Failure Class (NYHA) on 3-6 months of optimal medical therapy
Class I
No symptoms with ordinary physical activity
Class II
Symptoms with ordinary activity. Slight limitations of activity
Class III
Symptoms with less than ordinary activity. Marked limitation of activity
Class IV
Symptoms with any physical activity or event at rest.
Optimal Medications Include:
• Beta blockers
• Angiostensen converting enzyme (ACE) Inhibitor i.e. captopril, enalapril fosinopril
imidapril, lisinopril, moexipril, ramipril
• Angiotensin receptor blockers (ARB) i.e. candesartan, eprosartan, losartan, valsartan
• Statins
• Aspirin
Definition of other Clinical Indications
Hypertrophic cardiomyopathy:
Inherited heart muscle disorder. The main feature is excessive thickening of the heart muscle
without obvious cause. Thickening is seen in the ventricular septal measurement and in
weight. Arrhythmias are a common complication.
Long QT Syndrome:
Familial disease characterized by an abnormally prolonged QT interval and usually, by stressmediated life threatening ventricular arrhythmias.
Arrhthmogenic Right Ventricular Dysplasia (ARVD)
Characterized by arrhythmic manifestations, possible due to replacement of myocardium of
the right ventricle by fibroadipose tissue. ARVD should be considered as a cause of
ventricular tachycardia of left bundle branch block configuration and/or SCD, particularly
during exercise in young subjects. The ECG may show anterior precordial T wave inversion,
particularly in lead V3 and /or QRS complex duration > 110ms in the right precordial leads.
Brugada’s Syndrome:
46
December 2004
An arrhythmogeic disorder associated with high risk of SCD in individuals with structurally
normal hearts. Characterized by transient right bundle branch block and ST segment
elevation in leads V1-V3.
47
December 2004
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