Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Longstanding Persistent Atrial Fibrillation (CRYO-AF)

Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Longstanding Persistent Atrial Fibrillation

Evaluation of the Cardioblate CryoFlex Surgical Ablation System in Subjects With Longstanding Persistent Atrial Fibrillation Requiring Mitral Valve Surgery

Studies have shown that taking drugs to stay out of AF has limited success. This research is designed to study heart rhythm after surgical therapy, namely by measuring if there are benefits to having surgery to treat Atrial Fibrillation (AF) with the Cardioblate CryoFlex Surgical Ablation System. The system is approved and commercially available with CE mark. The purpose of this study is to support clinical evidence that the Cardioblate System is safe and effective to treat AF.

Introduction: Among the cardiac arrhythmias, Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population and represents an increasing problem worldwide. Management strategies for AF include combinations of various treatments, including surgery. Cox et al. developed the surgical Maze procedure to restore sinus conduction to the AV node and to restore effective, synchronized bi-atrial contraction. In an effort to address the observed challenges and make this treatment available to more subjects, modifications of the Maze pattern and new lesion patterns have being developed and tested. Devices using new technologies, like cryothermia, were developed in an effort to reduce the time required to make the lesion pattern.The Cardioblate® CryoFlex™ Surgical Ablation System has been successfully used for the surgical ablation of cardiac arrhythmias including atrial fibrillation. The system utilizes cryothermia to create the linear lesions of the surgical Maze-III procedure. Purpose: To provide clinical evidence showing that the Cox Cryo Maze III procedure is effective and safe in subjects with longstanding persistent AF undergoing mitral valve repair or replacement. Study objective: The study objectives were to characterize the safety and efficacy of the Medtronic Cardioblate CryoFlex Surgical Ablation System when used to treat subjects with longstanding persistent AF requiring concomitant mitral valve repair or replacement.

Subjects with longstanding persistent AF undergoing Maze III procedure using the Cardioblate CryoFlex Surgical Ablation System concomittant to Mitral valve surgery. During surgery, a Medtronic Reveal XT Insertable Cardiac Monitor was implanted to monitor future episodes of AF.

Longstanding persistent AF was treated with the Cox Cryo Maze III procedure During mitral valve surgery a surgical ablation was performed, using the Cardioblate CryoFlex Surgical Ablation System. In addition, the Medtronic Reveal XT Insertable Cardiac Monitor, was implanted.

During the procedure, a Medtronic Reveal XT Insertable Cardiac Monitor was implanted to monitor episodes of AF during follow-up period

Efficacy: Percentage of Treated Subjects Diagnosed With Longstanding Persistent AF Off Class I or III Antiarrhythmic Drugs and Out of AF at 12 Months, and Who Did Not Receive Additional Ablation Therapy for AF Prior to the 12-month Evaluation.

The primary efficacy endpoint was defined as the percentage of subjects diagnosed with longstanding persistent AF off Class I or III antiarrhythmic drugs and out of AF, as determined by Reveal XT recordings (AF burden < 0.5% per 24h) at 12 months and who did not receive additional ablation therapy for AF prior to the 12-month evaluation. An additional ablation therapy could include percutaneous catheter ablation or AV nodal ablation (cauterizing or freezing the AV node). Cardioversions were allowed only during the 12 week blanking period.

Safety: Rate of Device and Procedure Related Acute Major Adverse Events (MAE) Within 30 Days Post-procedure or Prior to Hospital Discharge, Whichever Came Last

The composite MAE was defined as a subject experiencing any of the following adverse events: Stroke Transient ischemic attack (TIA) Pulmonary embolism Peripheral arterial embolism Myocardial infarction (MI) Mediastinitis Esophageal injury Death Cardiac injury related to the use of the Cardioblate CryoFlex System that required additional surgical or catheter intervention

AF Burden in Subjects Diagnosed With Longstanding Persistent AF as Measured by Reveal XT Recordings at 3, 6 and 12 Months

Assessment of Quality of Life as Measured by the SF-12 at Baseline, 6 and 12 Months After the Procedure

The 12-Item Short Form Health Survey (SF-12) is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. Ten summary scores are reported from the SF-12. The scale range for each of the ten subscales is from 0 to 100, with higher scores corresponding to a better outcome. Subjects average unit score (with standard deviation) are reported at baseline, 6 and 12 months. As unit of measure we used units on a scale.

Rate of Device and Procedure Related Acute Major Adverse Events (MAE) Within 12 Months Post-procedure or Prior to Hospital Discharge, Whichever Came Last

The composite MAE was defined as a subject experiencing any of the following adverse events: Stroke Transient ischemic attack (TIA) Pulmonary embolism Peripheral arterial embolism Myocardial infarction (MI) Mediastinitis Esophageal injury Death Cardiac injury related to the use of the Cardioblate CryoFlex System that required additional surgical or catheter intervention

Inclusion Criteria: Patients must have a documented history of longstanding persistent AF as defined by the HRS/EHRA/ECAS Guidelines Patients should have a concomitant indication (other than AF) for open-heart surgery for mitral valve repair or replacement (bioprosthesis) Patients should be older than or equal to 18 years of age Exclusion Criteria: Atrioventricular reentrant tachycardia (AVRT) NYHA Class = IV Left ejection fraction of ≤ 30% Need for emergent cardiac surgery (i.e. cardiogenic shock) or redo open heart surgery Previous atrial fibrillation ablation, AV-nodal ablation, or surgical Maze procedure Contraindication for anticoagulation therapy Left atrial diameter > 7.0 cm Preoperative need for intra-aortic balloon pump or intravenous inotropes Renal failure requiring dialysis or hepatic failure Life expectancy of less than one year Pregnancy or desire to be pregnant within 12 months of the study treatment Current diagnosis of active systemic infection Documented MI 6 weeks prior to study enrollment