Heart Failure
Conditions
Keywords
Heart Failure, HF, Cardiac Resynchronization Therapy, CRT, Optimization, SmartDelay, Echocardiography, AV Delay
Brief summary
The primary objective of SMART-AV is to assess the effect of SmartDelay for determining optimal AV delay timing during CRT compared to both a fixed AV delay and echocardiography-determined optimal AV timing chronically over a 6-month period.
Detailed description
SMART-AV is a randomized, multi-center, double-blinded, non-significant risk, three-armed trial that will investigate the effects of optimizing AV delay timing in heart failure patients receiving CRT-D therapy. Patients will be randomized in a 1:1:1 ratio using randomly permuted blocks within each center. The study will compare chronic changes in structural and functional outcomes in CRT-D patients randomized to AV delay set as fixed, set with SmartDelay or determined by echocardiography. Patients will be followed at enrollment, implant, post-implant, 3-months post-implant and 6-months post-implant.
Interventions
DEVICEAV Delay programming through cardiac resynchronization therapy
All subjects in this trial receive the same device. For the purpose of this trial. intervention is programming of the atrio-ventricular (AV) delay in the two treatment arms, while the control arm will receive AV delay programming from a Fixed nominal setting. Echo optimized and Algorithm optimized are the treatment arms programmed to receive optimized AV delay settings and will be compared to the Fixed nominal arm.
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who meet current indications for a BSC CRT-D device with the SmartDelay algorithm * Patients who are willing and capable of undergoing a device implant and participating in all testing associated with the SMART-AV Study * Patients who are on optimal and stable pharmacologic therapy * Patients who are expected to be in sinus rhythm at the time of implant * Patients who have a life expectancy of more than 360 days, per physician's discretion * Patients who are geographically stable and willing to comply with the required follow-up schedule * Patients who are 18 years of age or above, or of legal age to give informed consent specific to state and national law
Exclusion criteria
* Patients who are in complete heart block, or who otherwise are unable to tolerate pacing at VVI-40 RV for up to 14 days * Patients undergoing an upgrade of a pacemaker or implantable cardioverter-defibrillator who are unable to tolerate pacing at VVI-40 RV for up to 14 days * Patients who have previously received cardiac resynchronization therapy * Patients who are expected to receive a heart transplant or have other cardiac surgeries or procedures planned during the course of the study * Patients who currently have or who are likely to receive a tricuspid valve prosthesis * Patients who have a neuromuscular, orthopedic, or other non-cardiac condition that prevents normal, unsupported walking * Patients who are pregnant or planning to become pregnant during the study * Patients who are currently enrolled in another investigational study or registry that would directly impact the treatment or outcome of the current study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular End-systolic Volume (LVESV) | 6 months | Change in square root of absolute left ventricular end systolic volume from baseline to 6 month follow up |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints Will Include Structural and Functional Measures | Chronic |
Countries
United States
Participant flow
Pre-assignment details
1060 patients were enrolled. 46 patients were not implanted with a CRT-D: screening failures (27), withdrawn by physician/sponsor (15) or withdrew consent (4). 34 implanted patients were not randomized: screening failures (13), withdrawn by physician/sponsor (14), withdrew consent (4), LTFU (2), death (1), not properly randomized (3)
Participants by arm
| Arm | Count |
|---|---|
| Fixed AV Delay Patients programmed to a Fixed nominal AV delay of 120 ms with a sensed AV offset set to 0 and the LV offset set to 0 | 325 |
| Echo Optimized AV Delay Echo optimized AV delay (Iterative Method), LV offset is optional | 323 |
| Algorithm Optimized AV Delay Algorithm optimized AV delay with sensed and paced AV delay recommendations and LV offset set to 0 | 332 |
| Total | 980 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 6 | 15 | 7 |
| Overall Study | Lost to Follow-up | 20 | 12 | 24 |
| Overall Study | Unavailable or unreadable 6 month LVESV | 18 | 14 | 18 |
Baseline characteristics
| Characteristic | Fixed AV Delay | Echo Optimized AV Delay | Algorithm Optimized AV Delay | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 189 Participants | 189 Participants | 200 Participants | 578 Participants |
| Age, Categorical Between 18 and 65 years | 136 Participants | 134 Participants | 132 Participants | 402 Participants |
| Age Continuous | 66.4 years STANDARD_DEVIATION 10.6 | 65.8 years STANDARD_DEVIATION 11.2 | 66.1 years STANDARD_DEVIATION 11.3 | 66.1 years STANDARD_DEVIATION 11 |
| Region of Enrollment Europe | 21 participants | 22 participants | 25 participants | 68 participants |
| Region of Enrollment United States | 304 participants | 301 participants | 307 participants | 912 participants |
| Sex: Female, Male Female | 114 Participants | 103 Participants | 97 Participants | 314 Participants |
| Sex: Female, Male Male | 211 Participants | 220 Participants | 235 Participants | 666 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 145 / 325 | 145 / 323 | 144 / 332 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Left Ventricular End-systolic Volume (LVESV)
Change in square root of absolute left ventricular end systolic volume from baseline to 6 month follow up
Time frame: 6 months
Population: Availability of baseline and 6 month echocardiograms with primary endpoint values (LVESV) among randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fixed AV Delay | Left Ventricular End-systolic Volume (LVESV) | -15 ml |
| Echo Optimized AV Delay | Left Ventricular End-systolic Volume (LVESV) | -19 ml |
| Algorithm Optimized AV Delay | Left Ventricular End-systolic Volume (LVESV) | -21 ml |
Comparison: Gate keeping strategy utilized for Type 1 error control described in design paper - negative results observed for initial comparisons - (each at alpha = .05) between fixed and algorithm optimized AV delay and fixed and Echo optimzied AV. Results from both of these comparisons were non-significant.p-value: 0.66ANOVA
Secondary
Secondary Endpoints Will Include Structural and Functional Measures
Time frame: Chronic