Adaptive CRT optimization at rest and during exercise

Protocol page 6-8.

Cardiac resynchronization therapy (CRT) results in symptomatic improvement,
reverse left ventricular remodeling and greater survival in patients with NYHA
class III/IV heart failure, low ejection fraction (<=35%) and prolonged QRS
duration (>120 ms). However, approximately 30% of CRT recipients show no
benefit with the therapy. Multiple studies have demonstrated that optimization
of CRT device atrio-ventricular (AV) and inter-ventricular (VV) delays can
further improve cardiac function acutely and result in better clinical
outcomes. Although consensus on the best optimization method is lacking,
echocardiographic optimization is most common in clinical practice. Yet, the
majority of CRT patients are not optimized, since the echocardiographic
procedure is time and resource-consuming and settings optimal during in-office
evaluation at rest may not be optimal at later times when the patient is active
or when chronic changes in cardiac structure and function take place.
The aCRT algorithm is designed to optimize the AV and VV delays easily,
automatically and continuously.

AdOpt CRT is designed to compare indices of cardiac function at device settings
optimized using an investigational Adaptive CRT (aCRT)
algorithm versus CRT with nominal programming. The comparison will be performed
during rest and submaximal exercise.

AdOpt CRT is a prospective, multi-center, non-randomized investigational study.
The duration of the study is expected to be approximately 1 year from the date
of the first enrollment. The study will be performed at up to 10 centers in
Europe, and is expected to enroll up to 50 subjects to meet the study
objectives.
Data are collected at baseline and during the exercise test. The test day must
take place within 14 days after the baseline visit. This could also be on the
same day. There is no futher follow-up of the patients.

Patients undergo an exercise stress test with ultrasound measurements and
continuous blood pressure measurement. They will also receive a Holter during
the test. The test is performed at different settings of the CRT-D.

Potential risks associated with participating in the study are:
• The operation of the algorithm aCRT may inadvertently cause a rapid and
irregular heart beat, which can feel uncomfortable.
• The aCRT algorithm may cause your CRT-D device does not provide therapy or
stimulate your heart so that the symptoms of heart failure (such as shortness
of breath, weakness) may be aggravated.
• It is possible that the aCRT algorithm does not work as planned and shuts
off.
• The aCRT algorithm may cause your CRT-D device accidentally gives a shock.
• There can be confusion about the operation of your device when someone not
familiar with the aCRTalgoritme, evaluates the device. This can lead to
inappropriate programming of the device.

Submaximal exercise may be associated with various side effects, which include
shortness of breath, fatigue, nausea, palpitations, chest pain and, in rare
instances, may be associated with the risk of myocardial infarction.