His-pacing and AV-node Ablation vs. Pulmonary Vein Isolation for Atrial Fibrillation (His-PAAF)

Physiological Pacemaker Treatment in Combination With AV Node Ablation Compared With Pulmonary Vein Isolation for Patients With Symptomatic Atrial Fibrillation - a Randomized Controlled Study

Objective To investigate if conduction system pacing ((CSP) i.e. atrioventricular node ablation + His bundle pacing or Left Bundle Branch pacing) is as good as (or better than) atrial fibrillation ablation with pulmonary vein isolation for older patients (70-85yrs) with symptomatic atrial fibrillation and at least moderately dilated left atrium.

Patient population:

90 patients aged 70-85 years with atrial fibrillation, referred to either AV node ablation or pulmonary vein isolation.

Primary endpoint:

Improvement in health-related quality of life as measured by the physical component summary (PCS) of the well-validated SF-36 form, at one year after AV node ablation + CSP or AF ablation.

Secondary endpoints:

Physical performance measured by 6-minute walk test, biochemical markers of heart failure (NT-ProBNP), frequency of complications, left ventricular systolic and diastolic function, and left atrial size evaluated after 12 months. Arrhythmia specific symptoms and anxiety will be measured with the ASTA and HADS questionnaires. Arrhythmia symptom correlation between subjective and objective findings. After three years, clinical endpoints will be evaluated regarding overall survival, and risk of heart failure hospitalization or death. The cost of the treatments will be compared, and estimated cost per quality adjusted year of life will be calculated, based on the EQ5D questionnaire.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Left Atrial Dilatation
• Intervention / Treatment: Procedure: Conduction System pacing and AV node ablation; Procedure: Atrial fibrillation ablation by pulmonary vein isolation

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rasmus Borgquist, MD PhD; Phone Number: +4646171010; Email: rasmus.borgquist@med.lu.se
• Study Contact Backup: Name: Cecilia Rorsman, MD; Email: Cecilia.Rorsman@regionhalland.se

Study Locations

• Sweden
  • Linköping, Sweden
    • Not yet recruiting
    • Linköping University
    • Contact: Ulla Walfridsson, RN PhD; Email: Ulla.walfridsson@regionostergotland.se
  • Lund, Sweden, 221 85
    • Active, not recruiting
    • Skåne University Hospital
  • Stockholm, Sweden
    • Active, not recruiting
    • Stockholm Arrhythmia Center
  • Varberg, Sweden
    • Recruiting
    • Varberg Hospital
    • Contact: Cecilia Rorsman, MD; Email: cecilia.rorsman@med.lu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Indication for invasive treatment of symptomatic atrial fibrillation according to current guidelines
• LVEF >35%
• Age 70-85 years
• Persistent atrial fibrillation, or paroxysmal atrial fibrillation with at least moderate enlargement of the left atrium (≥42ml/m2)
• Chronic and well-tolerated treatment with anticoagulants (either non-vitamin K oral anticoagulant or vitamin K antagonist)
• Willingness to participate, to understand the instructions and fill out the questionnaires, and ability to sign informed consent

Exclusion Criteria:

• Chronic atrial fibrillation with >1 year duration
• BMI >40kg/m2
• Hypertrophic cardiomyopathy
• Severe heart failure with symptoms ≥ NYHA class IIIb
• Heart amyloidosis
• Cardiac sarcoidosis
• Recent (<3 months) myocardial infarction
• Significant heart valve disease (pronounced insufficiency or stenosis)
• Pacemaker or ICD treatment ongoing, or current pacemaker indication
• Congenital heart disease that required surgical correction
• Comorbidity that is assessed significantly affect the patient's quality of life over the next year, or 3-year survival

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conduction System pacing plus AV node ablation; A His-pacing lead in combination with a backup RV pacing lead or an LBB pacing lead, and a right atrial lead (if needed) will be placed using standard technique. The His-pacing or LBB pacing lead will be Medtronic 3830, and the outer sheath will be either Medtronic C304 or C315 deflectable. If failure to implant with these tools, other leads and sheaths can be used at the discretion of the operator. A standard DDD pacemaker or CRT-P device from Medtronic will be used. A minimum of three weeks post-implant, the device will be interrogated and His-bundle threshold will be evaluated. A threshold of ≤2.0V@1.0ms is acceptable. If the device is well-functioning and successful His-pacing is documented, AV node ablation will be performed.	Procedure: Conduction System pacing and AV node ablation; See study arm description.
Active Comparator: Pulmonary vein isolation; Atrial fibrillation will be performed as a complete pulmonary vein isolation. Either Cryoballon or radio frequency ablation with irrigated tip contact force enabled catheter can be used. Pulsed field ablation can be used if available. Endpoint is complete electrical isolation of all pulmonary veins, verified by entry- and exit block using a multipolar catheter during pacing.	Procedure: Atrial fibrillation ablation by pulmonary vein isolation; See study arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related Quality of Life: questionnaire	Improvement in the Physical Component Summary (PCS) of the SF-36 questionnaire	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint: Proportion of patients with major adverse events	Proportion of patients with major adverse events that are devicerelated or related to ablation procedure (including but not limited to exit block, infection, perforation/tamponade, pericardial effusion, lead dislodgement, TIA/stroke, oesophago-atrial fistula, groin hematoma or vascular complication, pseudoaneurysm, phrenic nerve injury).	12 months
Mental Quality of Life: questionnaire	Improvement of the "mental" health related quality of life, measured by the mental component summary (MCS) of the SF-36 questionnaire	12 months
Arrhythmia related Quality of Life: ASTA questionnaire	Change in arrhythmia related quality of life as measured by the The Arrhythmia-Specific questionnaire in Tachycardia. The ASTA questionnaire consists of 13 items, each with a score of 0-4. A higher score denotes more symptoms associated with the arrhythmia. and Arrhythmia (ASTA) questionnaire	12 months
Anxiety and depression	Anxiety and depression symptoms, measured by the Hospital Anxiety and Depression Scale (HADS). The scale consists of 14 questions with 0 to 3 points for each, with a higher score denoting more depression/anxiety	12 months
Ejection fraction	Change in left ventricular systolic ejection fraction	12 months
Biomarker for heart failure	Change in NT-ProBNP level	12 months
Physical performance	Change in six minute walk test distance	12 months
Electrocardiography changes	Change in QRS duration on ECG	12 months
Health economy	Total atrial fibrillation and device related health care cost	12 months
Survival	Total survival and survival free of major complications	3 years
Hospitalization for heart failure	Risk of hospitalization for heart failure assessed by Kaplan Meier time dependent analysis using time from ablation to first hospitalization for heart failure within three years	3 years

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Rasmus Borgquist, MD PhD, Lund University, Skane University Hospital, Arrhythmia Section, Lund, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Quality of Life; Atrial fibrillation; Pulmonary vein isolation; AV node ablation; Left atrial dilatation; Conduction System pacing; Age group 70 to 85 years
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Arrhythmias, Cardiac; Atrial Fibrillation; Dilatation, Pathologic
• Other Study ID Numbers: His_PAAF_study

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