Adaptive Cardiac Resynchronization Therapy Optimization at Rest and During Exercise (AdOPT CRT)

Study Overview
=================
Brief Summary
-----------------
The AdOPT Cardiac Resynchronization Therapy (CRT) study is an acute, prospective, multi-center, non-randomized investigational study designed to compare indices of cardiac function at device settings optimized using the investigational Adaptive CRT (aCRT) algorithm versus nominal programming. The comparison will be performed during rest, atrial pacing and sub-maximal exercise. AdOPT CRT is a sub study of the Adaptive CRT Study (NTC00980057) being conducted in Europe.

Detailed Description
-----------------
Adaptive CRT is an implantable heart failure device feature that attempts to optimize CRT without echocardiographic testing.

Official Title
-----------------
Adaptive Cardiac Resynchronization Therapy Optimization at Rest and During Exercise (AdOPT CRT)

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Device: CRT pacing at rest and during exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is age 18 or greater Subject is willing to sign and date the study Informed Consent form Subject has been implanted with a clinically indicated CRT-D device (Medtronic Vision 3D or Protecta models) for at least 1 month but less than 7 months from the date of study enrollment Exclusion Criteria: Subject has a history of persistent or permanent AF for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted. Subject has atrial or ventricular tachyarrhythmias or frequent atrial or ventricular ectopy at the time of enrollment. Subject's resting heart rate at the time of enrollment exceeds 90 bpm. Subject had CRT system implanted for more than 7 months from the date of the study enrollment Subject has complete AV block. Subject had previous mechanical valve surgeries. Subject has congenital heart disease. Subject has contraindication for an exercise test. Subject is unable to perform a sub-maximal exercise test. It is not possible to acquire technically acceptable echocardiographic images. Subject has medical conditions that would limit study participation. Subject is pregnant (all women of child-bearing potential must undergo a pregnancy test within seven days prior to the study visit). Subject is enrolled in the Adaptive CRT study Subject is enrolled in concurrent studies which could confound the results of this study. Subject meets exclusion criteria required by local law

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRT pacing at rest and during exercise<br>Rest and sub-maximal exercise | Device: CRT pacing at rest and during exercise<br>* CRT pacing with aCRT settings and BiV pacing with nominal programming at rest and during submaximal exercise<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Volume at Rest | Difference in stroke volume (SV) between BiV pacing with aCRT settings and BiV pacing with nominal settings at rest. Biventricular pacing is a type of pacing that paces both the right and left ventricles of the heart. Stroke volume is the volume of blood pumped from a ventricle in one heart beat. | Test day visit (within 14 days of enrollment) | 
| Stroke Volume During Atrial Pacing. | Difference in SV between BiV pacing with aCRT settings and BiV pacing with nominal settings during atrial pacing. Atrial pacing occurs at 20 beats-per-minute (bpm) above the subject's resting heart rate. | Test day visit (within 14 days of enrollment) | 
| Stroke Volume During Sub-maximal Exercise. | Difference in SV between BiV pacing with aCRT settings and BiV pacing with nominal settings during sub-maximal exercise. Sub-maximal exercise is exercise performed at a level below maximum effort. The subject will perform sub-maximal exercise to achieve target heart rate close to 75% of the age-predicted maximal heart rate. | Test day visit (within 14 days of enrollment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Function With aCRT Settings at Rest | Difference in blood pressure (BP)-derived and echocardiogram (echo)-derived parameters of cardiac function between BiV pacing with aCRT settings and BiV pacing with nominal settings at rest. | Test day visit (within 14 days of enrollment) | 
| Cardiac Function With Nominal Settings at Rest. | Difference in BP-derived and echo-derived parameters of cardiac function between BiV pacing with nominal settings and intrinsic conduction at rest. | Test day visit (within 14 days of enrollment) | 
| Cardiac Function With aCRT Settings During Sub-maximal Exercise. | Difference in BP-derived and echocardiogram (echo)-derived parameters of cardiac function between BiV pacing with aCRT settings and BiV pacing with nominal settings during sub-maximal exercise. | Test day visit (within 14 days of enrollment) | 
| Cardiac Function With Nominal Settings During Sub-maximal Exercise. | Difference in BP-derived and echo-derived parameters of cardiac function between BiV pacing with nominal settings and intrinsic conduction during sub-maximal exercise. | Test day visit (within 14 days of enrollment) | 
| Electrical Conduction at Rest. | Electrical conduction will be evaluated at rest by measuring the subject's intrinsic atrio-ventricular (AV) interval. The AV interval is the amount time between the start of atrial contraction and the start of ventricular contraction. | Test day visit (within 14 days of enrollment) | 
| Electrical Conduction During Sub-maximal Exercise. | Electrical conduction will be evaluated during sub-maximal exercise by measuring the subject's intrinsic AV interval. | Time Frame: Test day visit (within 14 days of enrollment) |