Personalized Atrial Septostomy for Heart Failure (PAS)

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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure; Heart Failure, Diastolic
• Intervention / Treatment: Procedure: Personalized atrial septostomy with combined use of radiofrequency-ablation and balloon-dilation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100037
      • National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences,Fuwai Hospital
    • Beijing, Beijing, China, 100037
      • Yan Chaowu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years;
2. Symptomatic heart failure in NYHA class III or IV ambulatory;
3. Optimal medical therapy of heart failure according to European Society of Cardiology (ESC) guidelines for last 6 months;
4. LVEF ≥ 45%;
5. Elevated left heart filling pressures: left ventricular end-diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg at rest;
6. LVEDP or PCWP-Mean right atrial pressure (MRAP) ≥ 5 mmHg;
7. Systolic blood pressure ≥ 90 mmHg.

Exclusion Criteria:

1. Acute infection or sepsis;
2. Intra-cardiac mass, thrombus or vegetation;
3. Evidence of right heart failure (TAPSE < 14 mm);
4. Pulmonary hypertension (PASP > 60 mmHg);
5. Associated atrial septal defect or large patent foramen ovale with significant left to right shunt in rest;
6. TIA or stroke within the last 6 months;
7. Thromboembolic events within the last 6 months;
8. Hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy as cause of heart failure;
9. Valvular diseases requiring therapy according to current ESC guidelines;
10. Life expectancy < 1 year for non-cardiovascular reasons.

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: CURB procedure; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Chaowu Yan, PhD and MD, National Center for Cardiovascular Diseases

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: September 20, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: April 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Heart failure; atrial septostomy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: 2020-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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