Trial Outcomes & Findings for Conduction System Pacing Optimized Therapy (NCT NCT04905290)

Last Updated: 2025-04-15

Results Overview

Standard Deviation of Activation Times (SDAT) is a measurement of dyssynchrony, taken by the ECG belt. As described in the SDAT Acute Protocol (below) and intervention sections, percent change in SDAT from AV-only pacing was calculated for each patient-pacing configuration combination over the 5 AV delays. Within each patient the difference between CSPOT SDAT and CSP SDAT and the difference between CSPOT SDAT and BiV SDAT were taken. The mean of those differences across patients was calculated along with a 95% confidence interval.

Recruitment status

COMPLETED

Study phase

Target enrollment

60 participants

Primary outcome timeframe

At implant during acute protocol

Results posted on

2025-04-15

Participant Flow

Participant milestones

Participant milestones
Measure	Single Arm Patients will undergo 1) Conduction System Pacing Optimized Therapy (CSPOT) lead placement, then the 2) acute pacing protocol, and then 3) device implant. During the acute pacing protocol (step 2), all patients will undergo three types of pacing configurations and for each pacing configuration several delay settings, as defined in Assigned Interventions. For each intervention, defined as a unique combination of pacing configuration and delay setting, the protocol will alternate for several heartbeats between AV pacing and intervention (5 sections of AV pacing and 4 sections of intervention). For each set of 9, Left Ventricular dP/dt max will be calculated continuously, and Standard Deviation of Activation Time will be selected from one of the sections for atrial-only pacing and one of the intervention sections. Device implant (step 3) will be with either a CRT-D or CRT-P. Each patient's device will be programmed to CSPOT pacing. Patients will be followed for 6 months.
Overall Study STARTED	60
Overall Study Implant Attempt	55
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Arm Patients will undergo 1) Conduction System Pacing Optimized Therapy (CSPOT) lead placement, then the 2) acute pacing protocol, and then 3) device implant. During the acute pacing protocol (step 2), all patients will undergo three types of pacing configurations and for each pacing configuration several delay settings, as defined in Assigned Interventions. For each intervention, defined as a unique combination of pacing configuration and delay setting, the protocol will alternate for several heartbeats between AV pacing and intervention (5 sections of AV pacing and 4 sections of intervention). For each set of 9, Left Ventricular dP/dt max will be calculated continuously, and Standard Deviation of Activation Time will be selected from one of the sections for atrial-only pacing and one of the intervention sections. Device implant (step 3) will be with either a CRT-D or CRT-P. Each patient's device will be programmed to CSPOT pacing. Patients will be followed for 6 months.
Overall Study Adverse Event	4
Overall Study Death	2
Overall Study Withdrawal by Subject	4
Overall Study Physician Decision	2
Overall Study Lost to Follow-up	2
Overall Study Screen Failure	2
Overall Study Unsuccessful Procedure	2

Baseline Characteristics

Conduction System Pacing Optimized Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Arm n=60 Participants Patients will undergo 1) Conduction System Pacing Optimized Therapy (CSPOT) lead placement, then the 2) acute pacing protocol, and then 3) device implant. During the acute pacing protocol (step 2), all patients will undergo three types of pacing configurations and for each pacing configuration several delay settings, as defined in Assigned Interventions. For each intervention, defined as a unique combination of pacing configuration and delay setting, the protocol will alternate for several heartbeats between AV pacing and intervention (5 sections of AV pacing and 4 sections of intervention). For each set of 9, Left Ventricular dP/dt max will be calculated continuously, and Standard Deviation of Activation Time will be selected from one of the sections for atrial-only pacing and one of the intervention sections. Device implant (step 3) will be with either a CRT-D or CRT-P. Each patient's device will be programmed to CSPOT pacing. Patients will be followed for 6 months.
Age, Continuous	68.1 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	39 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	38 Participants n=5 Participants
Height	171.1 cm STANDARD_DEVIATION 10.5 • n=5 Participants
Weight	88.2 kg STANDARD_DEVIATION 18.9 • n=5 Participants
Systolic Blood Pressure	121.9 mm Hg STANDARD_DEVIATION 17.5 • n=5 Participants
Diastolic Blood Pressure	70.8 mm Hg STANDARD_DEVIATION 10.4 • n=5 Participants
NYHA Classification Class I	5 Participants n=5 Participants
NYHA Classification Class II	29 Participants n=5 Participants
NYHA Classification Class III	24 Participants n=5 Participants
NYHA Classification Class IV	1 Participants n=5 Participants
NYHA Classification Not Available	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At implant during acute protocol

Population: Subjects with SDAT measurements available for each pacing configuration.

Outcome measures

Outcome measures
Measure	SDAT Acute Protocol n=44 Participants For each intervention, data from 9 sections of atrial only pacing and intervention will be used, beginning with the atrial-only pacing that immediately precedes the first intervention section and ending with the atrial-only pacing immediately following the last intervention pacing section. The SDAT measurement will be taken during one of the 4 intervention pacing sections and one of the 5 atrial-only pacing sections. This will provide 1 pair of SDAT measurements for each patient-intervention combination. For each pair, the percent change from the atrial-only section to the intervention section will be computed. Within each patient, the percent changes calculated from the 5 AV delay settings (default, default + 30ms, default + 60ms, default - 30ms, default - 60ms) will be used to fit a quadratic curve. The minimum value from the fitted quadratic curve within the delay settings will be used as the SDAT measurement for that patient-pacing configuration combination.	QRS Less Than or Equal to 171ms Subjects who completed acute protocol with QRS width less than or equal to 171ms as measured by 12-lead ECG
Electrical Synchronization Response CSPOT vs CSP	15.18 Difference in percent change in SDAT Interval 4.26 to 26.09	—
Electrical Synchronization Response CSPOT vs BiV	17.04 Difference in percent change in SDAT Interval 4.32 to 29.76	—

PRIMARY outcome

Timeframe: At implant during acute protocol

Population: Subjects with LV dP/dt max measurements available for each pacing configuration

Left Ventricular (LV) dP/dt max, a measurement of the initial velocity of myocardial contraction. As described in the LV dP/dt max (below) and intervention sections, percent change in LV dP/dt max from AV-only pacing was calculated for each patient-pacing configuration combination over the 5 AV delays. Within each patient the difference between CSPOT SDAT and CSP SDAT and the difference between CSPOT SDAT and BiV SDAT were taken. The mean of those differences across patients was calculated along with a 95% confidence interval.

Outcome measures

Outcome measures
Measure	SDAT Acute Protocol n=41 Participants For each intervention, data from 9 sections of atrial only pacing and intervention will be used, beginning with the atrial-only pacing that immediately precedes the first intervention section and ending with the atrial-only pacing immediately following the last intervention pacing section. The SDAT measurement will be taken during one of the 4 intervention pacing sections and one of the 5 atrial-only pacing sections. This will provide 1 pair of SDAT measurements for each patient-intervention combination. For each pair, the percent change from the atrial-only section to the intervention section will be computed. Within each patient, the percent changes calculated from the 5 AV delay settings (default, default + 30ms, default + 60ms, default - 30ms, default - 60ms) will be used to fit a quadratic curve. The minimum value from the fitted quadratic curve within the delay settings will be used as the SDAT measurement for that patient-pacing configuration combination.	QRS Less Than or Equal to 171ms Subjects who completed acute protocol with QRS width less than or equal to 171ms as measured by 12-lead ECG
Hemodynamic Response CSPOT vs CSP	10.33 Difference in % change LV dP/dt max Interval 7.15 to 13.51	—
Hemodynamic Response CSPOT vs BiV	-1.31 Difference in % change LV dP/dt max Interval -4.75 to 2.13	—

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Subjects with LVEF measurements at both baseline and 6-month follow-up visit

Left ventricular ejection fraction will be measured, based on echocardiography, at the baseline visit and again at the 6-month follow-up visit. Change will be calculated as the value observed at baseline subtracted from the value observed at 6 months.

Outcome measures

Outcome measures
Measure	SDAT Acute Protocol n=35 Participants For each intervention, data from 9 sections of atrial only pacing and intervention will be used, beginning with the atrial-only pacing that immediately precedes the first intervention section and ending with the atrial-only pacing immediately following the last intervention pacing section. The SDAT measurement will be taken during one of the 4 intervention pacing sections and one of the 5 atrial-only pacing sections. This will provide 1 pair of SDAT measurements for each patient-intervention combination. For each pair, the percent change from the atrial-only section to the intervention section will be computed. Within each patient, the percent changes calculated from the 5 AV delay settings (default, default + 30ms, default + 60ms, default - 30ms, default - 60ms) will be used to fit a quadratic curve. The minimum value from the fitted quadratic curve within the delay settings will be used as the SDAT measurement for that patient-pacing configuration combination.	QRS Less Than or Equal to 171ms Subjects who completed acute protocol with QRS width less than or equal to 171ms as measured by 12-lead ECG
Left Ventricular Ejection Fraction (LVEF)	15.24 Change in percentage of LVEF Interval 10.16 to 20.32	—

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Subjects who had LVESV recorded at both baseline and the 6-month follow-up visit

Left ventricular end systolic volume will be measured, based on echocardiography, at the baseline visit and again at the 6-month follow-up visit. The change will be calculated as difference between the 6-month and baseline values, divided by the baseline value.

Outcome measures

Outcome measures
Measure	SDAT Acute Protocol n=35 Participants For each intervention, data from 9 sections of atrial only pacing and intervention will be used, beginning with the atrial-only pacing that immediately precedes the first intervention section and ending with the atrial-only pacing immediately following the last intervention pacing section. The SDAT measurement will be taken during one of the 4 intervention pacing sections and one of the 5 atrial-only pacing sections. This will provide 1 pair of SDAT measurements for each patient-intervention combination. For each pair, the percent change from the atrial-only section to the intervention section will be computed. Within each patient, the percent changes calculated from the 5 AV delay settings (default, default + 30ms, default + 60ms, default - 30ms, default - 60ms) will be used to fit a quadratic curve. The minimum value from the fitted quadratic curve within the delay settings will be used as the SDAT measurement for that patient-pacing configuration combination.	QRS Less Than or Equal to 171ms Subjects who completed acute protocol with QRS width less than or equal to 171ms as measured by 12-lead ECG
Left Ventricular End Systolic Volume (LVESV)	-43.28 percent change lvesv Interval -51.51 to -35.06	—

SECONDARY outcome

Timeframe: 6 months

Population: Subjects who had a successful implant procedure.

The Clinical Composite Score (CCS) is a validated 3-level categorical variable that can take the values - Improved, Unchanged, or Worsened - at each follow-up visit. It is based on mortality, HF events, termination of device function, NYHA score, and patient global assessment. Briefly, the scoring system is as follows: * A patient is considered "worsened" if they die, demonstrate a worsened NYHA class, report at least moderately worsened heart-failure symptoms, or are hospitalized or permanently discontinue therapy because of or associated with worsening heart-failure * A patient is considered "improved" if they have not "worsened" and either demonstrate improvement in NYHA class or report at least moderately improved heart-failure symptoms * A patient is considered "stabilized" if they have not "worsened" or "improved" * A patient is considered "unavailable" if they did not complete 6-month visit and was not "worsened"