ALternate Site Cardiac ReSYNChronization (ALSYNC) Study

Study Overview
=================
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.

Official Title
-----------------
ALternate Site Cardiac ReSYNChronization Study

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Device: Endocardial Left Ventricular pacing


Participation Criteria
=================
Eligibility Criteria
-----------------
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 exclusion criteria required by local law

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endocardial Left Ventricular pacing<br>All patients will undergo the intervention, and are followed at 1, 3, 6, and 12 months (minimum) and biannually thereafter until 1 year after enrollment of the last patient. | Device: Endocardial Left Ventricular pacing<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implant Success | Number of participants with a successful implant of Model 3830 lead. | Implant | 
| 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. | Implant | 
| 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. | 12 months | 
| 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 | 12 months | 
| 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 | 12 months | 
| 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 | baseline and 6 months | 
| 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 | 12 months | 
| 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 | baseline and 6 months | 
| 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 | 6 months | 
| 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 | baseline and 6 months | 
| 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 | baseline and 6 months | 
| 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 | baseline and 6 months |