Heart Failure
Conditions
Brief summary
The ALternate site cardiac reSYNChronization (ALSYNC) study, a non-comparative, prospective, non-randomized, multi-national clinical investigation. The purpose of this clinical investigation is to evaluate the safety and performance of the investigational atrial transseptal endocardial LV lead delivery system and the implant procedure for delivering the SelectSecure® Model 3830 lead into the Left Ventricle via a superior approach, and to evaluate the performance of the SelectSecure® Model 3830 lead in the Left Ventricle.
Detailed description
Cardiac resynchronization therapy (CRT) reduces mortality and the risk of heart failure decompensation and improves quality of life in indicated patients. However, many do not benefit due to failure to deliver the left ventricular (LV) lead via coronary sinus (5-10%) or lack of symptomatic improvement (30-40%). The purpose of the ALSYNC Study was to evaluate the feasibility and safety of LV endocardial (LVE) pacing using a Model 3830 lead implanted by a novel pectoral atrial transseptal lead delivery system.
Interventions
DEVICEEndocardial Left Ventricular pacing
Subjects receive an endocardial LV lead placement via superior approach using Medtronic Model 3830 lead and Medtronic Model 6227ATS deflectable delivery catheter and Medtronic Model 6248HS, 6248JL, or 6248JS delivery catheter, using trans esophageal echo (TEE) or intra-cardiac echo (ICE) to guide the 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
* Cardiac Resynchronization Therapy candidate/recipient with: * Failed Cardiac Resynchronization Therapy implant or required CRT replacement without viable access to Coronary sinus or, * Sub-optimal Coronary sinus anatomy per investigator discretion or, * Worsened or unchanged clinical status after Cardiac Resynchronization Therapy implant * Patients able and willing to take optimal Vitamin K antagonist therapy (International Normalized Ratio (INR) of 2-4) * Patients willing to sign and date the Patient Informed Consent form * Patients 18 years of age or older * Patients able and willing to comply with the protocol, and is expected to remain available for follow-up visits
Exclusion criteria
* Patients having contraindications to Vitamin K antagonist therapy * Patients contraindicated for \< 100 micrograms beclomethasone dipropionate * Patients unable to tolerate an urgent thoracotomy * Documented (previous) ischemic or hemorrhagic stroke * Patients with known previous atrial septal defect closure, or history of mural thrombus that has not been resolved * Patients with documented atrial fibrillation AND increased stroke risk as determined by the Congestive Heart Failure, Hypertension, Age(2), Diabetes, Stroke(2), Vascular disease, Age, and Sex Category (CHA2DS2-VASc) Score of equal to or greater than 5 * Patients with unstable angina pectoris or who have had an acute myocardial infarct within the past 30 days * Patients with known atrial septum defect (ASD) and/or left superior vena cava * Patient with known internal carotid artery stenosis of greater than 50% * Patients diagnosed with peripheral artery disease that are expected to undergo stenting within the next three months * Patients who have had a Coronary artery bypass graft or stent within the past three months * Patients with history of mitral or aortic valve repair or replacement * Post heart transplant patients (patients waiting for heart transplant are allowed in the study) * Patients currently undergoing dialysis treatment * Patients with ongoing chemotherapy and radiation therapy that may have an effect on cardiac function * Patients with ongoing Adverse Events from a previous Left Ventricle lead implant attempt * Patients enrolled in any concurrent drug and/or device study that may confound the results of this study * Patients who are not expected to survive more than twelve months * Patients with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Free From Lead, Delivery System and Implant Related Complications. | 6 months | Adverse events were reviewed by an independent Adverse Event Adjudication Committee. Events classified as complication related to the LV endocardial lead, the investigational delivery system or the implant procedure contribute to the outcome. The percentage of patients free from such complication at 6 months after the procedure was estimated using the Kaplan-Meier method and is reported with the corresponding 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bipolar Pacing Impedance of the Model 3830 Lead in the LV at 12 Months | 12 months | Measurement of Impedance of the Model 3830 Lead in the LV using the implanted device at the 12 month visit |
| Subjects With 1 Class of NYHA Improvement From Baseline to 6 Months | baseline and 6 months | NYHA Class change was evaluated between baseline and the 6 months visit. Reported are the subjects with at least 1 class improvement from baseline to 6 months |
| Implant Success | Implant | Number of participants with a successful implant of Model 3830 lead. |
| Number of Questionnaires Reporting None of the Handling and Implant Characteristics as Poor | Implant | Questionaires were collected for each LV lead implant attempt, reattempt, and LV lead modification. To evaluate the ease of positioning of the Model 3830 lead and the Models 6227ATS and 6248HS, JS, JL catheters, a rating scale of Poor, Fair, Good, Very good, and Excellent was used for each of the ten questions on the questionnaire. Outcome reports the number of questionnaires where no single question was answered with Poor. |
| Bipolar Sensing Amplitude of the Model 3830 Lead in the LV at 12 Months | 12 months | Sensing amplitude measurement was taken with the implanted device at the 12 month follow-up visit. |
| Distance Walked at 6 Minute Hall Walk at the 12 Month Visit | 12 months | Distance walked at the 6 minute hall walk test at the 12 month visit |
| Percent Change in Left Ventricular Ejection Fraction From Baseline to 6 Months | baseline and 6 months | Percent change in Left Ventricular Ejection Fraction (LVEF) was measured from baseline to 6 months |
| Milliliters Change in Left Ventricular End-Systolic Volume at 6 Months | 6 months | Milliliters change in Left Ventricular End-Systolic Volume (LVESV) from baseline to 6 months |
| Millimeters Change in Left Ventricular End-Diastolic Diameter From Baseline to 6 Months | baseline and 6 months | Millimeters change in Left Ventricular End-Diastolic Diameter (LVEDD) from baseline to 6 months |
| Number of Subjects With Mitral Regurgitation Improvement of at Least One Class From Baseline to 6 Months | baseline and 6 months | Reported is the number of patients with at least one class improvement from baseline to 6 months |
| Change in (NT-pro)BNP Levels From Baseline to 6 Months | baseline and 6 months | Change in either Brain Natriuretic Peptide (BNP) or N-Terminal-prohormone BNP (NT-proBNP) levels from baseline to 6 months |
| Bipolar Pacing Threshold of the Model 3830 Lead in the LV at 12 Months | 12 months | Bipolar measurement of Model 3830 lead voltage threshold at 0.4ms pulse width using the implanted device at the 12 month visit |
Countries
Belgium, Canada, France, Hungary, Italy, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Left Ventricular Endocardial Pacing All enrolled patients were scheduled to receive a CRT implantation with endocardial LV lead | 136 |
| Total | 136 |
Baseline characteristics
| Characteristic | Left Ventricular Endocardial Pacing |
|---|---|
| Age, Customized Age (years) | 66 years STANDARD_DEVIATION 10 |
| Atrial Fibrillation | 68 Participants |
| Left Bundle Branch Block (LBBB) | 94 Participants |
| Left Ventricular Ejection Fraction (LVEF) | 29 percentage STANDARD_DEVIATION 9 |
| New York Heart Association (NYHA) Class NYHA Class I | 4 Participants |
| New York Heart Association (NYHA) Class NYHA Class II | 29 Participants |
| New York Heart Association (NYHA) Class NYHA Class III | 93 Participants |
| New York Heart Association (NYHA) Class NYHA Class IV | 10 Participants |
| QRS duration | 165 milliseconds (ms) STANDARD_DEVIATION 32 |
| Sex/Gender, Customized Gender (male) | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 132 |
| other Total, other adverse events | 49 / 132 |
| serious Total, serious adverse events | 86 / 132 |
Outcome results
Primary
Percentage of Patients Free From Lead, Delivery System and Implant Related Complications.
Adverse events were reviewed by an independent Adverse Event Adjudication Committee. Events classified as complication related to the LV endocardial lead, the investigational delivery system or the implant procedure contribute to the outcome. The percentage of patients free from such complication at 6 months after the procedure was estimated using the Kaplan-Meier method and is reported with the corresponding 95% confidence interval.
Time frame: 6 months
Population: The Analysis cohort (132) includes the Baseline cohort (136) (Enrolled patients (138), excluding patients exited for eligibility violation without implant attempt and patients removed for major eligibility violation (2)), excluding patients that did not have implant attempt (4).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LV Endocardial Lead | Percentage of Patients Free From Lead, Delivery System and Implant Related Complications. | 82.2 percentage of patients |
Secondary
Bipolar Pacing Impedance of the Model 3830 Lead in the LV at 12 Months
Measurement of Impedance of the Model 3830 Lead in the LV using the implanted device at the 12 month visit
Time frame: 12 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 24 patients had a missing 12-months follow-up visit and 3 had a missing impedance measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Bipolar Pacing Impedance of the Model 3830 Lead in the LV at 12 Months | 596 Bipolar LV Pacing Impedance in Ohms | Standard Deviation 80 |
Secondary
Bipolar Pacing Threshold of the Model 3830 Lead in the LV at 12 Months
Bipolar measurement of Model 3830 lead voltage threshold at 0.4ms pulse width using the implanted device at the 12 month visit
Time frame: 12 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 24 patients had a missing 12-months follow-up visit and 4 had a missing bipolar pacing threshold measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Bipolar Pacing Threshold of the Model 3830 Lead in the LV at 12 Months | 0.84 Bipolar LV pacing threshold in Volts | Standard Deviation 0.27 |
Secondary
Bipolar Sensing Amplitude of the Model 3830 Lead in the LV at 12 Months
Sensing amplitude measurement was taken with the implanted device at the 12 month follow-up visit.
Time frame: 12 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 24 patients had a missing 12-months follow-up visit and 5 had a missing R-wave amplitude measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Bipolar Sensing Amplitude of the Model 3830 Lead in the LV at 12 Months | 11 Bipolar Sensing Amplitude in milliVolts | Standard Deviation 6.4 |
Secondary
Change in (NT-pro)BNP Levels From Baseline to 6 Months
Change in either Brain Natriuretic Peptide (BNP) or N-Terminal-prohormone BNP (NT-proBNP) levels from baseline to 6 months
Time frame: baseline and 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 22 patients had a missing (NTpro)BNP measurement at baseline and/or 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LV Endocardial Lead | Change in (NT-pro)BNP Levels From Baseline to 6 Months | NT-proBNP | 2554 change in picograms per milliliter | Standard Deviation 3485 |
| LV Endocardial Lead | Change in (NT-pro)BNP Levels From Baseline to 6 Months | BNP | 444 change in picograms per milliliter | Standard Deviation 587 |
Secondary
Distance Walked at 6 Minute Hall Walk at the 12 Month Visit
Distance walked at the 6 minute hall walk test at the 12 month visit
Time frame: 12 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 24 patients had a missing 12-months follow-up visit, and 18 did not complete the test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Distance Walked at 6 Minute Hall Walk at the 12 Month Visit | 391 Distance walked in meters | Standard Deviation 147 |
Secondary
Implant Success
Number of participants with a successful implant of Model 3830 lead.
Time frame: Implant
Population: The Analysis cohort (132) includes the Baseline cohort (136) (Enrolled patients (138), excluding patients exited for eligibility violation without implant attempt and patients removed for major eligibility violation (2)), excluding patients that did not have implant attempt (4).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LV Endocardial Lead | Implant Success | 118 Participants |
Secondary
Milliliters Change in Left Ventricular End-Systolic Volume at 6 Months
Milliliters change in Left Ventricular End-Systolic Volume (LVESV) from baseline to 6 months
Time frame: 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 27 patients had a missing LVESV measurement at baseline and/or 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Milliliters Change in Left Ventricular End-Systolic Volume at 6 Months | 121 LVESV change in milliliters | Standard Deviation 74 |
Secondary
Millimeters Change in Left Ventricular End-Diastolic Diameter From Baseline to 6 Months
Millimeters change in Left Ventricular End-Diastolic Diameter (LVEDD) from baseline to 6 months
Time frame: baseline and 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 17 patients had a missing LVEDD measurement at baseline and/or 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Millimeters Change in Left Ventricular End-Diastolic Diameter From Baseline to 6 Months | 63.7 millimeters change in LVEDD | Standard Deviation 9.9 |
Secondary
Number of Questionnaires Reporting None of the Handling and Implant Characteristics as Poor
Questionaires were collected for each LV lead implant attempt, reattempt, and LV lead modification. To evaluate the ease of positioning of the Model 3830 lead and the Models 6227ATS and 6248HS, JS, JL catheters, a rating scale of Poor, Fair, Good, Very good, and Excellent was used for each of the ten questions on the questionnaire. Outcome reports the number of questionnaires where no single question was answered with Poor.
Time frame: Implant
Population: Participants analyzed are those in the Analysis cohort as described before (132). The unit of analysis is a questionnaire for each attempted Model 3820 lead implant (139). In 7 cases their was a repeat procedure (reported as repeat implant attempt or system modification).
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| LV Endocardial Lead | Number of Questionnaires Reporting None of the Handling and Implant Characteristics as Poor | 75 questionnaire |
Secondary
Number of Subjects With Mitral Regurgitation Improvement of at Least One Class From Baseline to 6 Months
Reported is the number of patients with at least one class improvement from baseline to 6 months
Time frame: baseline and 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 16 patients had a missing MR measurement at baseline and/or 6 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LV Endocardial Lead | Number of Subjects With Mitral Regurgitation Improvement of at Least One Class From Baseline to 6 Months | 33 Participants |
Secondary
Percent Change in Left Ventricular Ejection Fraction From Baseline to 6 Months
Percent change in Left Ventricular Ejection Fraction (LVEF) was measured from baseline to 6 months
Time frame: baseline and 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 18 patients had a missing LVEF measurement at baseline and/or 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LV Endocardial Lead | Percent Change in Left Ventricular Ejection Fraction From Baseline to 6 Months | 36.1 Percent change in LVEF | Standard Deviation 12 |
Secondary
Subjects With 1 Class of NYHA Improvement From Baseline to 6 Months
NYHA Class change was evaluated between baseline and the 6 months visit. Reported are the subjects with at least 1 class improvement from baseline to 6 months
Time frame: baseline and 6 months
Population: Of the 118 patients that were successfully implanted with the Model 3830 lead in the LV, 13 patients had a missing 6-months follow-up visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LV Endocardial Lead | Subjects With 1 Class of NYHA Improvement From Baseline to 6 Months | 62 Participants |