Cardiac sympathetic nervous system function and activity as a predictor for appropriate ICD therapy in patients with chronic heart failure

Motivation
Adequate risk stratification tools to identify patients with chronic heart
failure who are most likely to benefit from implantable cardioverter
defibrillators (ICD) are lacking.

Background
Chronic heart failure (CHF) is a complex clinical syndrome characterized by
abnormal function of the ventricles and activation of neurohormonal
compensation mechanisms which is accompanied by effort intolerance, fluid
retention and reduced longevity. Especially activation of the sympathetic
cardiac activity is detrimental in CHF.
In Europe, the prevalence of CHF is estimated as about 1% (approximately 4
million patients in Western Europe), while in the United States, the number of
CHF patients is approximately 5 million.1-4 About $30 billion in costs, a
million hospitalizations and 55,000 deaths are directly attributed to CHF in
the United States of America (USA) annually. CHF is the only category of
cardiovascular diseases for which the prevalence, incidence, hospitalization
rate, mortality, and total burden of costs have increased in the past 25 years.
This is related to the increasing number of elderly patients with an impaired
left ventricular function. The incidence of CHF is approximately 1% of the
population and increases to 8% after the age 65. Due to the aging of the
population and the improved survival after acute myocardial infarction, it is
likely that the incidence of CHF and its impact on public health will continue
to increase.
Although pharmacological therapies for CHF have been successful in reducing
morbidity and mortality, sudden cardiac death (SCD) remains a leading cause of
death among these patients. Especially patients with severely reduced left
ventricular ejection fraction (LVEF) (<30-35%) are at risk. Implantable
cardioverter-defibrillators (ICD) as a primary or secondary prevention reduce
the relative risk for death by 20%. A rapid increase in the use of ICD therapy
as primary treatment for this condition has been demonstrated. This results in
an increasing burden on healthcare budgets in the USA and Europe. The MADIT II
study, however, showed that the actual reduction of fatal events was 5.6
percentage points (from 19.8 to 14.2). In addition, the SCD-HeFT trial showed
that the annual rate of ICD shock was 7.1% and of appropriate shock for rapid
ventricular tachycardia or ventricular fibrillation was 5.1%, with a total of
21% patients receiving appropriate shocks over 5 years. Since the majority of
patients in these studies remains without life-threatening arrhythmias, it is
of the utmost importance to find risk stratification tools to identify patients
most likely to benefit from ICD leading to higher cost-effectiveness.

Increased cardiac sympathetic activity, which is often present in patients with
chronic heart failure, may play a role in the development of ventricular
arrhythmias. High sympathetic activity has been demonstrated in CHF patients
with ventricular arrhythmias. On the other hand, beta-adrenoceptorantagonists
have shown to reduce the incidence of ventricular arrhythmias in CHF patients.
Therefore, cardiac sympathetic nervous function and activity may serve as
parameters that can be used to identify CHF patients who are at risk for
life-threatening arrhythmias. Some small clinical studies have shown that
cardiac sympathetic activity as assessed by the use of
123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy is related to sudden
cardiac death and appropriate ICD discharge.

The aim of this study is to identify CHF patients who are most likely to
benefit from ICD therapy by the use of clinical patient characteristics related
to CHF combined with a measure of myocardial sympathetic integrity/activity.
This will enable to discriminate responders from non-responders to ICD therapy
in heart failure.

This is a non-randomized, dual centre, observational prospective study.
Patients eligible for an ICD (both single-, dual chamber and biventricular ICDs
are allowed to enter the study) according to the latest guidelines will be
included. After implantation patients will be followed every six months for at
least 2 years. Data from the ICD memory log will be regularly downloaded at
these visits. Inclusion of patients will be performed in the first 12 months
after start of the study.

- The radiation burden is well within the international limits for participants
as formulated by the ICRP (2.5 mSv).
- There are no known side-effects of MIBG in the concentration administered to
the participants.