Clinical trial NCT05508256: CAtheter-Based Ablation of Atrial Fibrillation Compared to Conventional Treatment in Patients With Heart Failure With Preserved Ejection Fraction
Official title: CAtheter-Based Ablation of Atrial Fibrillation Compared to Conventional Treatment in Patients With Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Heart Failure With Preserved Ejection Fraction
Heart Failure With Mildly Reduced Ejection Fraction
Keywords: atrial fibrillation
heart failure
catheter ablation
medial therapy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
name: Kompetenznetz Vorhofflimmern e.V. (AFNET)
name: Boston Scientific Corporation
First posted: 2022-08-19
Enrollment: 1548
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The CABA-HFPEF is an investigator-initiated, prospective, parallel-group, randomized, open, blinded endpoint assessment, interventional multicenter strategy trial. CABA-HFPEF compares two treatment strategies that employ established therapies within their approved indications.
Primary purpose: TREATMENT

Brief summary: The objective of CABA-HFPEF is to test whether catheter ablation (CA) for atrial fibrillation (AF) can prevent adverse cardiovascular outcomes in patients with heart failure with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF).

Detailed description: HFpEF accounts for approximately half of HF diagnoses and HFmrEF adds another 20%. HFpEF patients are predisposed to AF with a prevalence of AF up to 65%. Conversely, the presence of AF increases the likelihood of subsequent HFpEF by up to 4-fold across diverse populations. The vulnerable hemodynamic state in HFpEF patients due to LV diastolic dysfunction can be significantly affected by AF with loss of atrial contraction and reduction in cardiac output. Thus, presence of AF in HFpEF patients leads to a significant increase in hospitalization, mortality and stroke.

Restoring and maintaining sinus rhythm in patients with HFpEF and AF could reduce cardiovascular (CV) outcomes. Catheter ablation (CA), particularly when performed as initial rhythm control, results in less recurrences of AF than anti arrhythmic drug therapy. In patients with HF with reduced ejection fraction (HFrEF) and AF, CA showed a significant reduction in all-cause mortality and worsening HF admissions compared to medical therapy.

No randomized clinical trial has tested or is currently testing the effects of CA on CV outcomes in patients with HFmrEF or HFpEF and AF. To address this, CABA-HFPEF tests whether CA can improve CV outcomes compared to usual care in these patients. The results of CABA-HFPEF will critically extend the current evidence on ablation-based rhythm control to this large population in dire need for treatments that improve clinical outcomes.

Eligibility criteria: INCLUSION CRITERIA:

1. Age ≥18 years
2. Signed written informed consent
3. Clinical evidence of symptomatic heart failure (NYHA Class II-III)
4. Paroxysmal or persistent atrial fibrillation (less than 24 months after first diagnosis, documented at least on one 12-lead ECG)
5. Left ventricular ejection fraction (LVEF) 40-49%

   OR

   LVEF ≥ 50% with at least one of the following HFpEF echocardiography findings (any local measurement made during the screening epoch):

   A. LA enlargement defined by at least 1 of the following: LA width (diameter) ≥3.8 cm or LA length ≥5.0 cm or LA area ≥20 cm2 or LA volume ≥55 ml or LA volume index ≥29 ml/m2

   B. Left ventricular hypertrophy (septal thickness or posterior wall thickness ≥1.1 cm or relative wall thickness \>0.42)
6. Patients with at least 1 of the following:

A. HF hospitalization (defined as HF listed as the major reason for hospitalization) within 6 months prior to screening visit and NT-proBNP \>200 pg/ml for patients in sinus rhythm (SR) or \>600 pg/ml for patients in AF at the time of blood sampling

B. NT-proBNP \>300 pg/ml for patients in SR or \>900 pg/ml for patients in AF on screening ECG

EXCLUSION CRITERIA:

1. Patient is unable or unwilling to provide infomed consent
2. Patient is not suitable for rhythm control of AF
3. Previous left atrial CA or surgical therapy of AF
4. Acutely decompensated HF, NYHA IV (patients can be enrolled after stabilization)
5. Valvular heart disease needing interventional or surgical treatment within 3 months
6. Heart surgery planned within 3 months
7. Prior heart transplant or listed for heart transplant or cardiac assist device implantation
8. Untreated hypothyroidism or hyperthyroidism (after successful treatment of thyroid dysfunction, patients may be enrolled)
9. Patient has absolute contra-indication to oral anticoagulation
10. Any disease that limits life expectancy to less than 1 year
11. Active systemic infection (after successful treatment of infection, patients may be enrolled)
12. Women currently pregnant or breastfeeding or women of childbearing potential without highly effective contraception (PEARL-Index \< 1%)
13. Patient is included in another clinical trial
14. Inability to comply with the study procedures

Primary outcomes:
measure: The primary outcome is defined as a composite of cardiovascular death, stroke and total (first and recurrent) unplanned cardiovascular hospitalization for heart failure or acute coronary syndrome.
timeFrame: Estimated first patient in to last patient out 48 months.
Secondary outcomes:
measure: All-cause mortality
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Cardiovascular death
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Stroke
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Total (first and recurrent) unplanned cardiovascular hospitalization for heart failure or acute coronary syndrome
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Unplanned hospitalization for atrial arrhythmia
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Total (first and recurrent) planned and unplanned cardiovascular hospitalizations
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Nights spent in hospital
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Days alive and out of hospital
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Atrial fibrillation burden (percentage of AF at 12 months FU Holter ECG)
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Change in left ventricular ejection fraction at 12 months FU
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Change in NYHA class at 12 months FU
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Change in EHRA score at 12 months FU
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
measure: Change in quality of life at 12 months FU
timeFrame: The secondary endpoints will be documented for at least 12 months following randomization. Estimated first patient in to last patient out 48 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité University Medicine Berlin, Campus Virchow Klinikum
Study officials:
affiliation: Head of Electrophysiology; Charité University Medicine Berlin, CVK
name: Abdul Parwani, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Director Department of Cardiology, Heart and Vascular Center University Hamburg Eppendorf
name: Paulus Kirchhof, Prof. Dr.
role: STUDY_CHAIR
affiliation: Department of Cardiology, Ludwig-Maximilians-University Hospital Munich
name: Stefan Kääb, Prof. Dr.
role: STUDY_CHAIR
affiliation: Departement of Medical Statistics, University Medical Center Göttingen
name: Tim Friede, Prof. Dr.
role: STUDY_CHAIR
affiliation: Head of Electrophysiology Department, University Hospital Lübeck
name: Roland Tilz, Prof. Dr.
role: STUDY_CHAIR
affiliation: Independent
name: Burkert Pieske, Prof. Dr.
role: STUDY_CHAIR
References: