Heart Failure
Conditions
Brief summary
The SYNSEQ study intends to assess the positive left ventricular dP/dt max achieved by MultiSpot LV pacing (either simultaneously or sequentially) in comparison to the response achieved by the current (standard) BiV pacing configuration in patients indicated/recommended for cardiac resynchronization therapy.
Detailed description
The following pacing configurations will be evaluated. Biventricular pacing (BiV): Pacing will be performed on one LV electrode pair, (at 3 different longitudinal locations), and on the tip of the RV-lead. In total, three different pacing BiV settings will be evaluated. Configuration 1: RV + LV lateral Apex, Configuration 2: RV + LV lateral Mid, Configuration 3: RV + LV lateral Base (Reference: Standard CRT) MultiSpot simultaneous LV-ventricular pacing (MultiSpot-SYN): Pacing will be performed on 3 electrodes on the LV wall, placed at different longitudinal locations, and on the tip of the RV-lead simultaneously. Configuration 4: RV + LV lateral Apex + LV lateral Mid + LV lateral Base MultiSpot sequential LV-ventricular pacing (MultiSpot-SEQ): 3 electrodes on the LV wall will be paced sequentially. The RV electrode will be paced simultaneously with last paced LV electrode.The timing-sequence and the amount of spots will depend on the electrical delays measured during the experiments. Configuration 5: LV lateral Apex =\> LV lateral Mid =\> LV lateral Base + RV
Interventions
PROCEDUREElectrophysiological Study
Subjects will receive pacing from one right ventricular lead and one left ventricular catheter/lead with multiple LV pacing spots during electrophysiological study procedure.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is indicated or recommended for CRT-P or CRT-D device according to current applicable ESC/AHA guidelines * Subject is in sinus rhythm * Subject receives optimal heart failure oral medical therapy * Subject is willing to sign the informed consent form * Subject is 18 years or older
Exclusion criteria
* Subject has permanent atrial fibrillation/flutter or tachycardia * Subject has pure right bundle branch block (= no additional left ventricular conduction delays) * Subject has left bundle branch block and QRS-duration of \> 150 ms and no sign of myocardial scar indicated by late gadolinium enhancement MRI * Subject experienced recent myocardial infarction, within 40 days prior to enrollment * Subject underwent valve surgery, within 90 days prior to enrollment * Subject is post heart transplantation, or is actively listed on the transplantation list * Subject is implanted with a left ventricular assist device * Subject has severe renal disease (up to physicians discretion) * Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure (≥ 2 stable infusions per week) * Subject has severe aortic stenosis (with a valve area of \<1.0 cm2 or significant valve disease expected to be operated within study period) * Subject has complex and uncorrected congenital heart disease * Subject has a mechanical heart valve * Pregnant or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth control * Subject is enrolled in another study that could confound the results of this study, without documented pre-approval from Medtronic study manager
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | Participants were followed for the time of the EP procedure, which had a median duration of 48 min | LV dP/dt max is a measurement of the initial velocity of myocardial contraction and is derivative of the LV-pressure. The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as (\[median dP/dt max during pacing On\] - (median baseline dP/dt max during pacing Off\])/\[median dP/dt max during pacing Off\]. From all percentage changes for a given pacing configuration and subject, a regression analysis is performed to determine the regression predicted highest percentage change. The presented percentage change is the average over all subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Percentage Change LV dP/dt Max and Percentage Change Blood Pressure | Participants were followed for the time of the EP procedure, which had a median duration of 48 min | Measured by invasive arterial blood line connected to a sensitive membrane displacement sensor. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected.The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as (\[median pressure during pacing On\] - (median pressure during pacing Off\])/\[median pressure during pacing Off\]. Correlation will be summarized over all pacing configurations and time points since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration or per time point. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation. |
| Correlation Between Percentage Change LV dP/dt Max and Percentage Change Non-Invasive Blood Pressure | Participants were followed for the time of the EP procedure, which had a median duration of 48 min | Acquired through finger volume clamp |
| Correlation Between Percentage Change LV dP/dt Max and Q-LV Ratio | Participants were followed for the time of the EP procedure, which had a median duration of 48 min | Derived from intra-cardiac leads (invasive) and surface electrodes (non-invasive) respectively. The Q-LV interval is defined as the time from the onset of the QRS width of the surface ECG to the first large positive or negative peak of the LV electrogram (EGM) during a cardiac cycle. The Q-LV ratio will be calculated as Q-LV/QRS duration. Correlation will be summarized over all pacing configurations since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation between % change LV dP/dt max and Q-LV ratio. |
| Correlation Between Percentage Change LV dP/dt Max and % Change QRS Width | Participants were followed for the time of the EP procedure, which had a median duration of 48 min | Derived from surface electrodes (non-invasive). The percentage change is determined as (\[QRS width during pacing On\] - (QRS width during pacing Off\])/\[QRS width during pacing Off\]. The correlation between % change LV dP/dt max and % change QRS width will be summarized over all pacing configurations since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration or per time point. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation. |
Countries
Poland, Slovakia, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Electrophysiological Study Subjects will receive pacing from one right ventricular lead and one left ventricular catheter/lead with multiple LV pacing spots during electrophysiological study procedure.
Electrophysiological Study: Subjects will receive pacing from one right ventricular lead and one left ventricular catheter/lead with multiple LV pacing spots during electrophysiological study procedure. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ECG acquisition error due to sweating | 1 |
| Overall Study | Electrical instability of patient | 1 |
| Overall Study | No veins available for lead placement | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Electrophysiological Study | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 19 Participants | — |
| Age, Categorical Between 18 and 65 years | 11 Participants | — |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 11.5 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Poland | 21 participants | — |
| Region of Enrollment Spain | 2 participants | — |
| Region of Enrollment Sweden | 1 participants | — |
| Region of Enrollment United Kingdom | 6 participants | — |
| Sex: Female, Male Female | 5 Participants | — |
| Sex: Female, Male Male | 25 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 2 / 31 |
| serious Total, serious adverse events | 3 / 31 |
Outcome results
Primary
Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec)
LV dP/dt max is a measurement of the initial velocity of myocardial contraction and is derivative of the LV-pressure. The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as (\[median dP/dt max during pacing On\] - (median baseline dP/dt max during pacing Off\])/\[median dP/dt max during pacing Off\]. From all percentage changes for a given pacing configuration and subject, a regression analysis is performed to determine the regression predicted highest percentage change. The presented percentage change is the average over all subjects.
Time frame: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
Population: The analysis population contains all subjects who completed electrophysiological study with analyzable data. For some patients not all pacing configurations were applied. Two patients missed Multispot sequential pacing and one patient missed BiV mid pacing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Electrophysiological Study | Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | BiV apical | 10.59 % change LV dP/dt max | Standard Error 2.56 |
| Electrophysiological Study | Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | BiV mid | 12.20 % change LV dP/dt max | Standard Error 2.06 |
| Electrophysiological Study | Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | BiV basal | 11.51 % change LV dP/dt max | Standard Error 2.15 |
| Electrophysiological Study | Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | Multispot simultaneous | 15.64 % change LV dP/dt max | Standard Error 3.31 |
| Electrophysiological Study | Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) | Multispot sequential | 11.80 % change LV dP/dt max | Standard Error 2.03 |
Secondary
Correlation Between Percentage Change LV dP/dt Max and % Change QRS Width
Derived from surface electrodes (non-invasive). The percentage change is determined as (\[QRS width during pacing On\] - (QRS width during pacing Off\])/\[QRS width during pacing Off\]. The correlation between % change LV dP/dt max and % change QRS width will be summarized over all pacing configurations since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration or per time point. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation.
Time frame: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
Population: The analysis population contains all subjects who completed electrophysiological study with analyzable data. For one patient no QRS width was available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Electrophysiological Study | Correlation Between Percentage Change LV dP/dt Max and % Change QRS Width | -0.28 Correlation coefficient |
Secondary
Correlation Between Percentage Change LV dP/dt Max and Percentage Change Blood Pressure
Measured by invasive arterial blood line connected to a sensitive membrane displacement sensor. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected.The percentage changes correspond to a percentage change between a pacing configuration (pacing on, e.g., Multispot pacing) and baseline (LV pacing off). There are several repetitions of pacing off and on for each pacing configuration. For one repetition, the percentage change is determined as (\[median pressure during pacing On\] - (median pressure during pacing Off\])/\[median pressure during pacing Off\]. Correlation will be summarized over all pacing configurations and time points since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration or per time point. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation.
Time frame: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
Population: All patients with analyzable LV dP/dt max data and analyzable and/or available blood pressure data. Two patients of the 25 patients with analyzable LV dP/dt max data did not have blood pressure data available or analyzable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Electrophysiological Study | Correlation Between Percentage Change LV dP/dt Max and Percentage Change Blood Pressure | Correlation between % change LV dP/dt max and SBP | 0.52 Correlation coefficient |
| Electrophysiological Study | Correlation Between Percentage Change LV dP/dt Max and Percentage Change Blood Pressure | Correlation between % change LV dP/dt max and DBP | 0.37 Correlation coefficient |
Secondary
Correlation Between Percentage Change LV dP/dt Max and Percentage Change Non-Invasive Blood Pressure
Acquired through finger volume clamp
Time frame: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
Population: The collection of non-invasive blood pressures was optional. During study execution, it was decided to not collect and/or analyze any non-invasive blood pressures.
Secondary
Correlation Between Percentage Change LV dP/dt Max and Q-LV Ratio
Derived from intra-cardiac leads (invasive) and surface electrodes (non-invasive) respectively. The Q-LV interval is defined as the time from the onset of the QRS width of the surface ECG to the first large positive or negative peak of the LV electrogram (EGM) during a cardiac cycle. The Q-LV ratio will be calculated as Q-LV/QRS duration. Correlation will be summarized over all pacing configurations since the interest is in the overall correlation between LV dP/dt max and other measurements, not in the correlation per pacing configuration. The general linear model as described in Blank & Altman, Biometrical Journal 310 (1995), p 446, was used to determine the correlation between % change LV dP/dt max and Q-LV ratio.
Time frame: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
Population: The analysis population contains all subjects who completed electrophysiological study with analyzable data. For five patients no Q-LV timings were available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Electrophysiological Study | Correlation Between Percentage Change LV dP/dt Max and Q-LV Ratio | 0.20 Correlation coefficient |