Trial Outcomes & Findings for Left Ventricular Synchronous Versus Sequential MultiSpot Pacing for Cardiac Resynchronization Therapy (CRT) (NCT NCT02914457)

NCT ID: NCT02914457

Last Updated: 2020-09-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 31 participants
• Primary outcome timeframe: Participants were followed for the time of the EP procedure, which had a median duration of 48 min
• Results posted on: 2020-09-25

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	31
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	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.
Overall Study Withdrawal by Subject	1
Overall Study Physician Decision	1
Overall Study No veins available for lead placement	1
Overall Study Electrical instability of patient	1
Overall Study ECG acquisition error due to sweating	1
Overall Study Protocol Violation	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Electrophysiological Study n=30 Participants 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.
Age, Categorical <=18 years	0 Participants n=30 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=30 Participants
Age, Categorical >=65 years	19 Participants n=30 Participants
Age, Continuous	66.4 years STANDARD_DEVIATION 11.5 • n=30 Participants
Sex: Female, Male Female	5 Participants n=30 Participants
Sex: Female, Male Male	25 Participants n=30 Participants
Region of Enrollment Sweden	1 participants n=30 Participants
Region of Enrollment Poland	21 participants n=30 Participants
Region of Enrollment United Kingdom	6 participants n=30 Participants
Region of Enrollment Spain	2 participants n=30 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Electrophysiological Study n=25 Participants 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.
Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) BiV apical	10.59 % change LV dP/dt max Standard Error 2.56
Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) BiV mid	12.20 % change LV dP/dt max Standard Error 2.06
Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) BiV basal	11.51 % change LV dP/dt max Standard Error 2.15
Percentage Change in Positive Left Ventricular dP/dt Max (mmHG/Sec) Multispot simultaneous	15.64 % change LV dP/dt max Standard Error 3.31
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 outcome

Timeframe: 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.

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.

Outcome measures

Measure	Electrophysiological Study n=23 Participants 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.
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 Interval 0.5 to 0.54
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 Interval 0.35 to 0.4

SECONDARY outcome

Timeframe: 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.

Acquired through finger volume clamp

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure

Electrophysiological Study n=20 Participants 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.

Correlation Between Percentage Change LV dP/dt Max and Q-LV Ratio

0.20 Correlation coefficient Interval -0.06 to 0.44

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure

Electrophysiological Study n=24 Participants 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.

Correlation Between Percentage Change LV dP/dt Max and % Change QRS Width

-0.28 Correlation coefficient Interval -0.44 to -0.1

Adverse Events

Enrolled Subjects

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Enrolled Subjects n=31 participants at risk All patients that signed informed consent will be summarized
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.2% 1/31 • Number of events 1 • Adverse events were collected from enrollment to study exit. Follow-up time (enrollment to exit) for subjects varied from 1 to 113 days.
Cardiac disorders Coronary artery disease	3.2% 1/31 • Number of events 1 • Adverse events were collected from enrollment to study exit. Follow-up time (enrollment to exit) for subjects varied from 1 to 113 days.
General disorders Lead dislogdement	6.5% 2/31 • Number of events 2 • Adverse events were collected from enrollment to study exit. Follow-up time (enrollment to exit) for subjects varied from 1 to 113 days.

Other adverse events

Measure	Enrolled Subjects n=31 participants at risk All patients that signed informed consent will be summarized
Injury, poisoning and procedural complications Cardiac vein dissection	6.5% 2/31 • Number of events 2 • Adverse events were collected from enrollment to study exit. Follow-up time (enrollment to exit) for subjects varied from 1 to 113 days.

Additional Information

Richard Cornelussen

Medtronic Bakken Research Center

Phone: +31433566651

Email: richard.cornelussen@medtronic.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60