Medical Discussions

by Vandana Khungur

Background

Sudden cardiac death (SCD) can occur in patients with CHF despite optimal medical therapy.

Patients with NYHA Class IV heart failure who are not candidates for cardiac transplantation are often excluded from studies such as SCD HeFT due to their high mortality from progressive pump failure.

There have been many more trials looking at primary prevention of SCD in ischemic than in nonischemic cardiomyopathy.

The national coverage determination (NCD) by the Center for Medicare and Medicaid Services for reimbursement of ICD therapy impacts patient selection in the US.

Briefly, and relevant to the article at hand, Medicare covers ICDs for pts with ischemic and non-ischemic dilated cardiomyopathy (if non-ischemic, >9 mos), NYHA Class II or III heart failure, and measured LVEF

1. Pts must not have cardiogenic shock or symptomatic hypotension while in a stable baseline rhythm
2. Pt must not have had a CABG or PTCA within the past 3 months
3. Pt cannot have had an MI within 40 days prior to ICD insertion
4. Pts may not have clinical symptoms or findings that would make them a candidate for coronary revascularization
5. Pts may not have any disease, other than cardiac disease (e.g., cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year.

Ischemic cardiomyopathy trials

Pts who have had an acute MI are at increased risk for SCD, usually due to a tachyarrhythmia.

MADIT I – Multicenter Automatic Defibrillator Implantation Trial

1st trial to demonstrate that ICDs can be used for primary prevention of SCD in high risk, asymptomatic pts
196 pts with prior MI, NSVT on monitoring, LVEF
At 27 month follow-up, findings were significant reductions in the incidence of overall mortality, cardiac mortality, and arrhythmic deaths in pts treated with ICDs. Subset analysis showed benefit only in high-risk pts with more severe heart disease (EF 0.12 sec). Benefit increased progressively with more risk factors.
ICD was compared to amiodarone without a control of no antiarrhythmic.
Based upon the results of MADIT I, the FDA approved the prophylactic use of the ICD in pts with the following:

1. Sustained VT induced by EPS and not prevented with IV procainamide
2. Ischemic heart disease
3. Prior MI
4. NSVT
5. Reduced LVEF (

MADIT II Trial
1232 pts with MI more than 30 days prior to enrollment (and more than 3 months if bypass surgery was performed) and LVEF

Pts were randomly assigned to a prophylactic ICD or conventional medical therapy.
The study was prematurely terminated at an average f/u of 20 months because the ICD reduced all-cause mortality (14.2 vs 19.8 % for conventional therapy, HR 0.65 (0.51-0.93). This survival benefit was entirely due to a reduction in sudden death and was present in all subgroups analyzed.
An unexpected finding was a higher rate of hospitalization for HF in the ICD group (20 vs 15%), possibly due to longer life spans in the ICD group due to prevention of SCD.

Another possible explanation for the increased hospitalization for HF is the development of myocardial injury and decreased LVEF after multiple ICD shocks.

CABG Patch Trial
This trial evaluated the efficacy of an epicardial ICD implanted at the time of CABG for reducing mortality in pts undergoing surgical revascularization for severe CHD who had LVEF

900 pts, no history of sustained VT or syncope. Average f/u of 32 months. 101 deaths in the ICD group (71 cardiac) and 95 in the control group (72 cardiac). HR of 1.07 was not statistically significant.

Prophylactic therapy with ICD did reduce arrhythmic death by 45%, but 71% of the deaths in the trial were nonarrhythmic, so this reduction in arrhythmic death did not impact upon total mortality.

ICD therapy potentially did not reduce mortality because coronary revascularization itself has a beneficial effect in preventing sudden death.

This trial is the main reason why current guidelines recommend against ICD implantation for pts who have recently undergone coronary revascularization.

MUSTT trial

704 pts with a prior MI (
2 year and 5 year rates for the primary end point were significantly lower for EPS guided therapy compared to no therapy, largely attributable to ICD therapy.

DINAMIT trial

Evaluated the role of prophylactic ICD implantation compared to no ICD in 674 pts with an MI within the preceding 6 to 40 days (unlike MADIT and MUSTT, which enrolled pts at least 3 weeks post MI).

LVEF 80 beats/min).

Exclusion criteria included sustained VT >48 hrs post-MI, NYHA class IV HF, or CABG or three vessel PCI post-MI.

No difference in annual all-cause mortality between ICD and control.

Arrhythmic deaths were more frequent in the control arm, nonarrhythmic deaths were more freqent in the ICD arm.

Potential reasons for less of an effect in this trial than in MADIT and MUSTT include that some SCDs in the early postinfarction period are due to recurrent ischemia, which is not completely treated by ICD discharge or ICD implantation may be riskier in pt immediately post MI.

This trial is the main reason that current guidelines recommend that ICD implantation should be deferred until at least 40 days post MI.

Nonischemic cardiomyopathy trials
Ventricular arrhythmias are common in HF pts with a nonischemic cardiomyopathy.

CAT and AMIOVIRT
Neither trial showed survival benefit of prophylactic ICD insertion compared to placebo or amiodarone.

CAT or Cardiomyopathy Trial, randomly assigned 104 pts with recent onset (

AMIOVIRT trial compared an ICD, sometimes with amiodarone, to amiodarone alone in 103 pts with moderate to severe nonischemic dilated cardiomyopathy with class I to III heart failure, LVEF

There was no significant difference in overall survival between the amiodarone and ICD groups at one year or three years.

Both trials were very small, AMIOVIRT did not have a placebo group and both had unexpectedly low mortality rates.

DEFINITE
458 pts enrolled, all received standard medical therapy, including an ACE and beta blocker in most instances.
Almost significant trend toward a reduction in the primary end point of all-cause mortality with an ICD (7.9 vs 14.1%, HR 0.65 (0.4-1.06). In the subset of NYHA Class III pts the difference was significant.

The trial was underpowered and may have shown a significant difference with more study subjects.

Cost-effectiveness of ICD implantation

Cost-effectiveness of ICD implantation for primary prevention of SCD is difficult to determine because there are several variables that enter the equation. The cost of device implantation, cost of generator change, projected life expectancy, and mortality rate, as well as efficacy of ICD therapy all matter. Quality of life adjustments are also factored in. A study entitled “ Cost-effectiveness of implantable cardioverter-defibrillators” Sanders et al., NEJM 20005; 353:1471, estimated cost-effectiveness of prophylactic ICD implantation. Use of an ICD was projected to add one to three quality adjusted life-years (QALYs), with a cost per quality-adjusted year of life saved from $34,900 in MADIT to $70,200 in SCD-HeFT. These costs all fall within the range of $50,000 to $100,000 per QALY gained that is considered to be acceptable in the US.