BIO monitoring in patients with preserved left ventricular function after diagnosed acute Myocardial
Infarction.

Survivors of AMI who have a severely impaired left ventricular ejection
fraction (LVEF) are at high risk of dying suddenly due to cardiac arrhythmias.
CARISMA was the first study to use implantable cardiac monitors (ICMs) for
continuous ECG monitoring of cardiac arrhythmias in the post-MI setting
including patients with LVEF * 40 % and still represents the only experience in
this area. This study documented unexpectedly high incidences of new-onset
atrial fibrillation (AF), high degree atrioventricular (AV) block, sinus
bradycardia, ventricular tachycardia (VT) and ventricular fibrillation (VF).
In summary, 46 % of all patients presented with at least one of the
pre-specified cardiac arrhythmias of which 85 % were asymptomatic. With a mean
follow-up duration of two years, 20 % of patients experienced a major adverse
cardiac event (MACE) including death or hospitalization due to heart failure,
re-infarction and stroke. More than 80 % of them were diagnosed with an
arrhythmia before the event. Hence, a cardiac arrhythmia was the most powerful
predictor of a MACE. The study, however, left it open whether preventive
treatment based on ICM detections will decrease the incidence of cardiovascular
events in high-risk patients. The assessed high incidences and prognostic
significance of cardiac arrhythmias underline the importance of continuous
rhythm monitoring in high risk patients after AMI. ICMs provide a much more
detailed picture of the incidence of brady- and tachyarrhythmias than
conventional follow-up. In addition, newer ICMs (e.g. BioMonitor) include
improved
algorithms that allow distinguishing different arrhythmias, and also the
diagnosis of normofrequent AF, compared to earlier devices such as those used
in the CARISMA study. A unique feature of the BioMonitor is the implemented
BIOTRONIK Home Monitoring® function which allows remote access to the
subcutaneous electrocardiogram (sECG) recordings. It has been suggested that
remote monitoring significantly increases the efficacy of the ICM. The CARISMA
study included patients within severly depressed LVEFs * 40 %. However, 80-90 %
of patients surviving AMI have a relatively preserved LVEF and are therefore
assumed to be at lower risk for MACE and arrhythmias. While this group as a
whole may have a relatively benign prognosis, this may not be justified in
subgroups with additional cardiovascular risk factors, particularly increasing
age, hypertension and diabetes. Moreover, reduced LVEF is less frequent after
introduction of percutaneous coronary intervention (PCI) and addition of
multiple antithrombotic agents after revascularization. In a recent study
including 1500 unselected consecutive patients with AMI most of the premature
deaths due to cardiovascular cause occurred in the group of patients with
relatively preserved LVEF but with other risk factors. Thus, there is a
clinical need to identify patients at high risk for MACE and arrhythmias with
preserved or only mildly reduced cardiac function but other cardiovascular risk
factors in place. The BIO|GUARD-MI study has been planned to address this need.
It was therefore
crucial to implement a tool for risk stratification beyond LVEF to correctly
identify patients at high risk after AMI.
Although the CHADS2-score has been designed to estimate the stroke risk in
patients with AF, evidence has been provided that the score is highly
prognostic as a risk stratification tool for both MACE and arrhythmias in
patients with LVEF * 40 % after AMI. In this population the risk of
experiencing a MACE was 8 times higher, and the risk of any arrhythmia was 3.7
times increased in patients with CHADS2-score * 3 compared to CHADS2-score = 0.
Also in other populations, the CHADS2-score is connected to the risk of AFand
bradyarrhythmias. Moreover, the individual components of the CHADS2-score
(congestive heart failure, hypertension, age, diabetes, stroke) have also been
found to be independently associated with increased risk of VT/VF and are all
known to be independent risk factors for worse outcome in patients after AMI.
In recent years, the CHA2DS2-VASc-Score has superseded the CHADS2-score for its
original purpose of stroke risk estimation in AF patients due to a better
performance especially in patients with a low risk. Both scores are based on
the same items, with the CHA2DS2-VASc-Score adding points for age above 75
years, female gender and vascular disease. Although more data are available on
the general cardiovascular risk prediction of the older CHADS2-Score, it is
justified to assume that the CHA2DS2-VASc-Score will perform similarly well for
the purpose of this study. Because the CHADS2-score is perceived as outdated
and inferior by many cardiologists, the CHA2DS2-VASc-Score will be used as main
entry criterion of this study.
Compatible with the conclusions drawn from CARISMA, large randomized controlled
trials have firmly established that post-MI patients with LVEF * 35% benefit
from the implantation of an ICD, which is reflected in current guidelines.
However, also patients with a preserved or mildly reduced LVEF (* 35%) but with
additional cardiovascular risk factors, such as those expressed within the
CHA2DS2-VASc-Score, may be considered at high risk for experiencing both
cardiac arrhythmias and consequent MACE. Nevertheless, scientific studies in
this population remain sparse. The BIO|GUARD-MI study therefore aims to
investigate whether continuous arrhythmia monitoring and detection, using an
ICM (BioMonitor) in patients after AMI with LVEF > 35 % but other
cardiovascular risk factors, decreases the risk of MACE if patients are
appropriately examined and treated for the observed arrhythmias.

The objective of the the BIO|GUARD-MI study is to investigate whether the early
diagnosis of cardiac arrhythmias, provided by the BioMonitor in connection with
remote monitoring, and the consequent treatment of the patient will decrease
the risk to experience a MACE in patients with AMI, CHA2DS2-VASc-Score * 4 in
men / * 5 in women and LVEF > 35 %.

Prospective, controlled, randomized, parallelgroup, open, multi-center,
international study

The BioMonitor group receives an implantable cardiac monitor - the BioMonitor

6-montly telephone contact using a quality of life questionnaire (WHO-5),
health questionniare (EQ-5D-5L) and questions focused on endpoint related data
(e.g. cardiovascular hospitalizations).

For the BioMonitor group there is the risk for complications related to the if
invasive implantation procedure. Known risks and complications are: bleeding,
swelling or pain at implant wound, infections and/or local tissue reaction,
device migration. see protocol paragraph 6