Atrial Fibrillation (AF), Mitral Valve (MV) Regurgitation
Conditions
Keywords
Atrial fibrillation, Mitral valve regurgitation, Mitral valve repair, Catheter ablation
Brief summary
CABA-MiTRA-AFNET12 is a non-commercial, parallel-group, prospective, randomised, open, blinded endpoint assessment (PROBE), multi-centre, therapy strategy trial. The trial investigates patients with severe mitral valve regurgitation who have undergone transcatheter edge-to-edge mitral valve repair (M-TEER) and have concomitant atrial fibrillation (AF). The objective is to assess whether catheter ablation of AF is superior to standard-of-care treatment in patients after TEER in reduction of major adverse cardiovascular and cerebrovascular events (MACCE).
Detailed description
The occurrence of atrial fibrillation (AF) as the most frequent arrhythmia is associated with an increased risk of stroke, acute coronary syndrome, heart failure, and cardiovascular death. AF is often associated with mitral valve regurgitation (MR) which represents the most frequent valvular heart disease in an elderly population. Both entities are not only linked by a complex pathophysiologic interplay but also the incidence of both is expected to increase due to the demographic factors, aging and obesity. AF is also a frequent comorbidity in patients with mitral valve regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) with an incidence between 33-53% in randomized controlled trials. This is of particular clinical relevance due the complex and deleterious interaction between AF, MR, and left ventricular dysfunction. AF may pronounce left ventricular systolic dysfunction and enhance functional MR by mitral annulus dilatation (3). Current data has shown that AF contributes markedly to the course of functional MR and determines an unfavourable outcome. Catheter ablation (CA) for AF in the setting of congestive heart failure (CHF) has recently been demonstrated to be associated with a prognostic benefit in all stages of systolic left ventricular heart failure (heart failure with reduced ejection fraction, HFrEF). Although, the benefit of rhythm control in general, but also after surgical mitral valve repair (MVR) has been shown data in the setting of AF in TEER is sparse. In a recent multi-center observational cohort, the outcome of patients undergoing CA before or after TEER was investigated. As a proof of concept, it was shown that CA was associated with a prognostic benefit outweighing the negative influence of AF. Thus, the present study aims at investigating the prognostic relevance of CA following TEER in a randomized, prospective design.
Interventions
OTHERUsual Care
Usual care will consist of optimal AF and heart failure therapy based on guideline recommendations and local protocols and usage. Individual treatment decisions will be taken by the site teams, considering the approved instruction for use (IFU) of medical devices and summary of product characteristics (SmPC) of all approved medications in patients with AF. The choice of therapies and medications follows routine care in line with medical guidelines and local policies at the discretion of the treating physician and should be based on the individual medical status of each study patient.
OTHERPulmonary Vein Isolation
Patients randomised to AF ablation will undergo pulmonary vein isolation using a safe and effective technology within 30 days after randomisation.
Sponsors
Atrial Fibrillation Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
blinded endpoint assessment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with ECG-documented atrial fibrillation (AF). * Transcatheter edge-to-edge mitral-valve repair (TEER) for severe functional mitral valve regurgitation (MR) with successful result (less than moderate MR, gradient \< 5 mmHg) performed within a period of minimum of 30 days and a maximum of 6 months. Moderate residual MR is eligible if no further mitral valve intervention or surgery is planned and patient is stable for \> 3 months. * Provision of signed informed consent.
Exclusion criteria
* Age \<18 years * Patient not suitable for AF ablation * Previous ablation procedure for AF * Acute coronary syndrome, cardiac surgery, angioplasty, or cerebrovascular accident within 2 months prior to enrolment * Untreated hypothyroidism or hyperthyroidism requiring therapy * Enrolment in another randomised study * Indication for cardiac resynchronization therapy * Current pregnancy, breastfeeding, or women not using reliable contraceptive measures during fertility age * Mental or physical inability to participate in the study * Planned cardiovascular intervention or operation * Life expectancy ≤ 12 month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of cardiovascular complications related to AF | Throughout study completion, estimated at a median follow-up period of 33 months. | It is defined as the time from randomisation to the first occurrence of (1) a composite of cardiovascular death, ischemic stroke or systemic embolic event,hospitalisation for heart failure (MACCE) and/or (2) death of any cause in a hierarchical order. |
| The Primary Safety Outcomes are the occurrence of AF ablation associated serious adverse events, hemorrhagic stroke, and non-serious adverse events of special interest. | Throughout study completion, estimated at a median follow-up period of 33 months. | Serious Adverse Events (SAEs), including primary and secondary outcome parameters if based on clinical events, will be adjudicated by the independent Clinical Event Committee (CEC) according to standardised definitions given in the CEC charter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to individual components of first primary endpoint (MACCE) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Time to ECG documented AF recurrence | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Time to ILR documented AF recurrence (AF burden sub-study) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Time to any documented AF recurrence | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| AF burden assessed in the AF burden (ILR) sub-study | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Atrial arrhythmias assessed in the AF burden (ILR) sub-study | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Other arrhythmias assessed in the AF burden (ILR) sub-study | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Total number of ECG documented AF recurrences | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Quality of life changes at 12 and 24 months compared to baseline (assessed by KCCQ-12) | From Enrollment to month 24. | — |
| Quality of life changes at 12 and 24 months compared to baseline (assessed by AFEQT) | From Enrollment to month 24 | — |
| Quality of life changes at 12 and 24 months compared to baseline (assessed by EQ-5D-5L) | From Enrollment to month 24. | Quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L): The resulting score of the UK index ranges from 1 (for the best state) to - 0.285 (for the worst state). EQ5D- VAS: visual-analogue scale (0 worst to 100 best). |
| MoCA-test score changes at 12 months compared to baseline | From Enrollment to month 12 | — |
| Heart failure progression (pro-BNP) at 12 months compared to baseline | From Enrollment to month 12. | — |
| Heart failure progression (NYHA) at 12 months compared to baseline | From Enrollment to month 12 | — |
| ECHO: LA size assessed at 12 months, and if available at 24 months and further yearly FU visits as changes to baseline | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| ECHO: LA volume assessed at 12 months, and if available at 24 months and further yearly FU visits as changes to baseline | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| ECHO: LV size assessed at 12 months, and if available at 24 months and further yearly FU visits as changes to baseline | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| ECHO: LV function assessed at 12 months, and if available at 24 months and further yearly FU visits as changes to baseline | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| ECHO: MR grading assessed at 12 months, and if available at 24 months and further yearly FU visits as changes to baseline | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Time to AF progression (documented as clinically evaluated) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Time to AF regression (documented as clinically evaluated) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Number of required re-M-TEER procedures over the entire follow-up duration | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Number of total ablations procedures over the entire follow-up duration | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Number of nights spent in hospital (per year) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
| Number of ablation procedures per patient (including the index ablation procedure in the early AF ablation group) | Throughout study completion, estimated at a median follow-up period of 33 months. | — |
Countries
Germany
Contacts
CONTACTVincent Beuger, PhD
CONTACTSabine Jürgensmeyer, PhD
STUDY_DIRECTORLars Eckardt, MD
University Hospital Münster
STUDY_DIRECTORDaniel Steven, MD
University Hospital Cologne
STUDY_DIRECTORReza Wakili, MD
University Heart and Vascular Center Frankfurt
STUDY_DIRECTORStephan Willems, MD
Asklepios Hospital St. Georg
Outcome results
None listed