Personalized Atrial Septostomy for Heart Failure

Study Overview
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Brief Summary
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This study aims to investigate the safety and efficacy of personalized atrial septostomy (PAS) with combined use of radiofrequency-ablation and balloon-dilation (CURB) in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).

Detailed Description
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Atrial septostomy is an important palliative therapy in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) . Though the safety of balloon atrial septostomy (BAS) is satisfactory, the incidence of spontaneous closure is higher, which limits the clinical utilization of this procedure. The device-implantation improves the long-term patency. However, the created fenestration is limited with fixed size and it is further complicated with the potential device-related complications. Radiofrequency catheter ablation (RFA) has the potential to cause irreversible damage around the rim of fenestration created with BAS, which might prevent the re-adhesion of the septal remnants. In addition, RFA on fossae ovalis might reduce the elastic recoil of local tissue and contribute to create larger inter-atrial fenestration with same BAS procedure. Therefore, the combined use of radiofrequency-ablation and balloon-dilation (CURB) might become a novel procedure to create a stable inter-atrial fenestration. In this study, the adult patients who have HFrEF and HFpEF refractory to medical therapy may be eligible for this study.

Official Title
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Personalized Atrial Septostomy With Combined Use of Radiofrequency-ablation and Balloon-dilation: First-in-human Study in Heart Failure

Conditions
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Heart Failure, Heart Failure, Diastolic

Intervention / Treatment
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* Procedure: Personalized atrial septostomy with combined use of radiofrequency-ablation and balloon-dilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Symptomatic heart failure in NYHA class III or IV ambulatory; Optimal medical therapy of heart failure according to European Society of Cardiology (ESC) guidelines for last 6 months; LVEF ≥ 45%; Elevated left heart filling pressures: left ventricular end-diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg at rest; LVEDP or PCWP-Mean right atrial pressure (MRAP) ≥ 5 mmHg; Systolic blood pressure ≥ 90 mmHg. Exclusion Criteria: Acute infection or sepsis; Intra-cardiac mass, thrombus or vegetation; Evidence of right heart failure (TAPSE < 14 mm); Pulmonary hypertension (PASP > 60 mmHg); Associated atrial septal defect or large patent foramen ovale with significant left to right shunt in rest; TIA or stroke within the last 6 months; Thromboembolic events within the last 6 months; Hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy as cause of heart failure; Valvular diseases requiring therapy according to current ESC guidelines; Life expectancy < 1 year for non-cardiovascular reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: After left and right catheterization, CURB procedure will be performed in all patients. The first step is RFA on fossae ovalis; and then graded BAS is carried out after transseptal puncture; finally, RFA is repeated around the fenestration-rim created with BAS. The fenestration-size will be determined based on the levels of AOP and MLAP, and the immediate size of fenestration will be evaluated with intra-cardiac echocardiography. The patency and size of fenestration will be followed up for 12 months. During the period of follow up, the other evaluations will include the improvement in exercise tolerance, major adverse cardiac and/or cerebrovascular events (MACCE), reduction of PAWP/MLAP at rest, cardiac remodeling, myocardial injury, and so on.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CURB procedure<br>Personalized atrial septostomy with combined use of radiofrequency-ablation and balloon-dilation (CURB) | Procedure: Personalized atrial septostomy with combined use of radiofrequency-ablation and balloon-dilation<br>* After left and right catheterization, CURB procedure will be performed in all patients. The first step is RFA on fossae ovalis; and then graded BAS is carried out after transseptal puncture; finally, RFA is repeated around the fenestration-rim created with BAS. The fenestration-size will be determined based on the level of MLAP, and the immediate size of fenestration will be evaluated with intra-cardiac echocardiography. The patency and size of fenestration will be followed up for 6 months. During the period of follow up, the other evaluations will include the improvement in exercise tolerance, major adverse cardiac and/or cerebrovascular events (MACCE), reduction of PAWP/MLAP at rest, cardiac remodeling, myocardial injury, and so on.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical change | Distance in 6 minutes walk test | 12 months | 
| The size of created-fenestration | The change of created-fenestration size evaluated with echocardiography | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of subjects who experience major adverse cardiac and cerebrovascular events (MACCE) | Peri-procedural, and 12 months MACCE and systemic embolic events in patients after CURB procedure. | 12 months | 
| Change of PAWP or MLAP at rest | Pulmonary capillary wedge pressure (PCWP)/MLAP at rest evaluated with right heart catheterization | 12 months | 
| Change of cardiac remodeling | The change in cardiac chamber and function evaluated with MSCT and CMR | 12 months | 
| Myocardial remodeling | The myocardial molecular imaging evaluated with PET-CT | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure; atrial septostomy