Conduction System Pacing Optimized Therapy (CSPOT)

Conduction System Pacing Optimized Therapy Study

The purpose of the CSPOT study is to determine the best mode of cardiac resynchronization therapy (CRT) pacing for different populations of CRT patients, comparing traditional biventricular or left ventricular pacing (BiV), conduction system pacing (CSP)-only, and conduction system pacing optimized therapy (CSPOT) also known as a combination of conduction system pacing (CSP) and left ventricular (LV) pacing. Additionally, safety of the system will be assessed.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Device: Left ventricular coronary sinus (BiV) configuration; Device: Conduction system pacing-only configuration; Device: Conduction System Pacing Optimized Therapy (CSPOT) configuration

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, D18 AK68
    • Beacon Hospital
• Poland
  • Katowice, Poland, 40-635
    • Górnośląskie Centrum Medyczne im prof Leszka Gieca Śląskiego Uniwersytetu Medycznego w Katowicach
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Swindon, United Kingdom, SN3 6BB
    • Great Western Hospital
• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Cardiovascular Institute of the South
  • Minnesota
    • Mounds View, Minnesota, United States, 55112
      • Medtronic Inc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is willing and able to provide written informed consent
• Subject is at least 18 years of age
• Patient is willing and able to comply with the protocol, including follow-up visits
• The patient's medical records must be accessible by the enrolling site over the follow-up period
• Standard CRT-D or CRT-P indications, with a preference for IVCD and non-LBBB patients, where LBBB is defined according to Strauss criteria.
• De-novo CRT implant, including upgrade from pacemaker or ICD

Exclusion Criteria:

• Subject has persistent or permanent AF (Atrial Fibrillation)/AFL (Atrial Flutter)
• Subject has 2nd or 3rd degree AV (Atrioventricular) Block
• Subject has RBBB with no additional conduction block
• Subject has intrinsic (non-paced) QRS width less than or equal to 120 ms
• Subject experienced MI 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 LV assist device
• Subject has severe renal disease
• Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure
• Subject has severe aortic stenosis (with a valve area of <1.0 cm or significant valve disease expected to be operated within study period)
• Subject has severe aortic calcification or severe peripheral arterial disease
• Subject has complex and uncorrected congenital heart disease
• Subject has mechanical heart valve
• Pregnant or breastfeeding woman (pregnancy test required for woman of child-bearing potential and who are not on a reliable form of birth regulation method or abstinence)
• Subject is enrolled in another study that could confound the results of this study without documented pre-approval from Medtronic study manager

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Device: Left ventricular coronary sinus (BiV) configuration; For subjects with a pacemaker, pacing of the left ventricular coronary sinus only. For subjects with a defibrillator, biventricular pacing of the left ventricular coronary sinus and the right ventricle. During the acute protocol, the five AV delays for this intervention include the default AV delay setting, default + 30 milliseconds (ms) AV delay, default + 60 ms AV delay, default - 30ms AV delay, default - 60ms AV delay. Patients with a defibrillator will receive two additional delays LV precedes default by 30ms and LV precedes default by 60ms.; Device: Conduction system pacing-only configuration; Conduction System Pacing (CSP) of the left bundle branch. During the acute protocol, the five AV delays for this intervention include the default AV delay setting, default + 30 milliseconds (ms) AV delay, default + 60 ms AV delay, default - 30ms AV delay, and default - 60ms AV delay.; Device: Conduction System Pacing Optimized Therapy (CSPOT) configuration; A combination of Left Ventricle pacing and Conduction System Pacing of the left bundle branch. During the acute protocol, the eight delays for this intervention include the default AV delay setting, default + 30 milliseconds (ms) AV delay, default + 60 ms AV delay, default - 30ms AV delay, default - 60ms AV delay, CSP precedes default by 30ms, LV precedes default by 30ms and LV precedes default by 60ms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrical Synchronization Response	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.	At implant during acute protocol
Hemodynamic Response	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.	At implant during acute protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction (LVEF)	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.	Baseline and 6 months
Left Ventricular End Systolic Volume (LVESV)	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.	Baseline and 6 months
Clinical Composite Score (CCS)	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"	6 months
Absolute Percent Change in SDAT by QRS Subgroup	Percent change in SDAT (as described in Primary Outcome 1: Arm/Group Description) by baseline QRS subgroup for each pacing configuration CSP, BiV, CSPOT during acute protocol at implant. The QRS subgroups were subjects with QRS width greater than 171ms and QRS width less than or equal to 171ms as measured by 12-lead ECG	At Implant during acute protocol
Absolute Percent Change in SDAT Split by Subjects With Pure LBBB and With Other Conduction Disorders	Percent change in SDAT (as described in Primary Outcome 1: Arm/Group Description) split by subjects with pure Left Bundle Branch Block (LBBB) and with other Conduction Disorders for each pacing configuration CSP, BiV and CSPOT during acute protocol.	At Implant during acute protocol
Absolute Percent Change in SDAT Split by Subjects With Ischemic Cardiomyopathy and Those With Non-Ischemic Cardiomyopathy	Absolute Percent change in SDAT (as described in Primary Outcome 1: Arm/Group Description) split by subjects with Ischemic Cardiomyopathy and those with Non-Ischemic Cardiomyopathy for each pacing configuration CSP, BiV and CSPOT during acute protocol.	At Implant during acute protocol
Percent Change in LV dP/dt Max Split by Subjects With Ischemic Cardiomyopathy and Those With Non-Ischemic Cardiomyopathy	Percent change in LV dP/dt max (as described in Primary Outcome 2: Arm/Group Description)split by subjects with Ischemic Cardiomyopathy and those with Non-Ischemic Cardiomyopathy for each pacing configuration CSP, BiV and CSPOT during acute protocol.	At Implant during acute protocol
Percent Change in LV dP/dt Max Split by Subjects With Pure Left Bundle Branch Block (LBBB) and With Other Conduction Disorders (NIVCD)	Percent change in LV dP/dt max (as described in Primary Outcome 2: Arm/Group Description) split by subjects with pure Left Bundle Branch Block (LBBB) and with other Conduction Disorders (NIVCD) for each pacing configuration CSP, BiV and CSPOT during acute protocol	At Implant during acute protocol
Improvement in LV dP/dt Max by QRS Subgroup	Percent change in LV dP/dt max (as described in Primary Outcome 2: Arm/Group Description) by QRS subgroup for each pacing configuration CSP, BiV and CSPOT during acute protocol. The QRS subgroups were subjects with QRS width greater than 171ms and QRS width less than or equal to 171ms as measured by 12-lead ECG	At Implant during acute protocol

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2021
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): November 2, 2023

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: MDT20029

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes