Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery, 10 year follow up.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Treatment of AF
is challenging, despite increasing pharmacological and technological treatment
options. Despite state-of-the-art pharmacological therapies targeting the
ventricular rate or aiming to restore sinus rhythm (SR), many patients with AF
stay symptomatic. Pulmonary vein isolation (PVI) through catheter or surgical
ablation has become the primary treatment modality for individuals
necessitating invasive intervention. PVI has shown favorable outcomes,
particularly in cases of paroxysmal AF. However, its efficacy in advanced AF,
encompassing persistent AF, enlarged left atria, or previous unsuccessful
ablations, remains limited, with a reported freedom from AF at one year after
surgical ablation of 69% in persistent AF cases.

In pursuit of enhancing treatment efficacy, various strategies have been
advocated, including partial atrial denervation through ablation of the major
autonomic ganglion plexus (GP). The autonomous nervous system, especially the
GPs, plays an important role in initiating AF. Activity of the GP,
characterized by both parasympathetic and sympathetic stimulation, has been
implicated in AF induction through mechanisms involving triggered firing and
early afterdepolarizations.

However, the AFACT trial, a large RCT in minimally invasive AF surgery
patients, examined the efficacy of GP ablation in patients with advanced AF and
found no reduction in AF recurrence up to one and two years. To the contrary,
it revealed an elevated incidence of major procedural complications, including
bleeds necessitating procedure termination or sternotomy, as well as an
increased need for pacemaker implantations due to sinus node dysfunction and AV
block.

Long-term follow-up data on GP ablation for AF remain sparse. An observational
study examining the seven year outcomes of GP ablation in addition to
thoracoscopic PVI compared to PVI alone in a group of permanent AF patients,
demonstrated decreasing success rates over time in both groups. Remarkably, the
addition of GP ablation to the maze procedure exhibited a significantly lower
rate of AF recurrence over a prolonged period exceeding seven years.

Similarly, long-term follow-up data on minimally invasive thoracoscopic AF
ablation without GP ablation remain sparse. A recent retrospective cohort study
evaluated AF recurrence at 10 years after the procedure, finding that only 42%
of a cohort of 22 persistent AF patient were in sinus rhythm, while 58%
experienced a recurrence of AF. Despite the high recurrence rate, the study
noted an improvement in the quality of life compared to pre-procedure levels.
While these findings address crucial issues, several key questions remain
unanswered. The study focused on the presence of AF at the 10-year mark rather
than freedom from AF over the decade, leaving the question of long term freedom
from AF after thoracoscopic AF ablation unresolved. Additionally, the
retrospective nature and small cohort size further limit the generalizability
of the results.

Currently, There are no data available on long-term efficacy and safety of GP
ablation versus no GP ablation. Furthermore, long-term follow-up data in
thoracoscopic AF ablation in general are very limited. The potential benefits
of GP ablation might become more apparent over extended periods, highlighting
the need for further investigation into its long-term efficacy and safety
profiles.

Primary Objective:
The study aims to assess freedom from AF ten years after the procedure without
the use of antiarrhythmic drugs in patients who underwent thoracoscopic
ablation in advanced AF with or without GP ablation.

Secondary Objectives:
1. To assess the progression of AF from paroxysmal to persistent or from
persistent to permanent over the ten-year follow-up period.
2. To evaluate changes in left atrial volume and function ten years following
the procedure.
3. To assess the quality of life of patients ten years after the procedure.
4. To assess the number and underlying reasons for pacemaker implants between
the two study arms during the ten-year follow-up period.
5. To evaluate the frequency and reasons for additional ablation procedures
during the ten-year follow-up period.
6. To determine the incidence of major adverse events such as heart failure,
stroke, major bleeding, and mortality during the follow-up period.
7. To determine and compare the causes of death during the ten year follow-up.
8. To assess freedom of AF since initiation of the last dose of AAD.

Participants in the AFACT trial will be included in this study, which consists
of three parts: an examination of the national mortality database (BRP/NRO), a
prospective cohort study, and a retrospective chart review.

National database examination
Given the age of the population involved, a significant proportion may have
deceased since the initial trial. To prevent distress to relatives that could
arise from attempting to communicate with deceased individuals, we will
cross-reference the national mortality database to identify deceased
participants.

Prospective cohort study
Participants of the AFACT trial will be sent a patient information folder.
These patients will be invited to the outpatient clinic to sign informed
consent. Subsequently, participants will be assessed during a single visit with
an investigator. Alongside the clinic visit, patients will receive a 12-lead
electrocardiogram (ECG), a 24-hour Holter ECG, a transthoracic echocardiogram
(TTE), and a laboratory assessment. If a recent (within the last two years)
Holter ECG, TTE or laboratory investigation with the required measurements is
available, the investigation will not be repeated. Patients will also be
requested to complete an SF-36 quality of life questionnaire. Any abnormalities
identified during the clinic visit or diagnostic investigations will be
promptly reviewed by a cardiologist, and patients will be referred for further
evaluation as deemed necessary.

Retrospective chart review
In the retrospective chart review phase, we will review the medical charts of
study participants to gather clinical event data from the years between the
AFACT trial procedure and the present. We will combine data obtained from
medical chart reviews of the Amsterdam UMC and all other hospitals that the
patient attended in AF during the last ten years.
Data collection will include all available electrocardiograms (ECGs) and Holter
ECGs obtained during the follow-up period of approximately ten years,
documenting occurrences of atrial fibrillation (AF), atrial flutter, and atrial
tachycardia. We will specifically attempt to obtain the first documented
recurrences of AF since the AFACT study so between 2 and 10 years follow up.
Additionally echocardiograms and laboratory assessments from the previous two
years will be collected. Furthermore, we will screen for incidences of major
cardiovascular adverse events, in particular strokes, bleeding, myocardial
infarctions and hearth failure hospitalizations. The general practitioners of
the included patients will be asked for additional data sources, such as
hospital admissions previously unknown to the researchers.

Burden:
- Discomfort of measurements: participants may experience discomfort from the
Holter monitoring and venipuncture.
-Time commitment: Participating in the research requires additional time from
the participant.
-Incidental findings: It is possible that incidental findings may be discovered
during the examinations that are not directly relevant to the research but may
be important for the participant's health.

Risks:
-Venipuncture for Laboratory Investigation:
Minimal Risks: The procedure carries minimal risks, primarily hematoma and
prolonged bleeding.
Risk Mitigation: This is one of the most common invasive procedures in
medicine and serious complications are rare. The risk of complication is
minimized by ensuring the procedure is performed by licensed medical
practitioners according to local standards.
-Echocardiography and Rhythm Monitoring:
Risk-Free: These diagnostic procedures are non-invasive and carry no risks.

Benefits:
- Additional Control Visit: Patients receive an extra control visit dedicated
to investigating cardiac abnormalities and conducting physical examination.
This enhances monitoring and early detection of potential issues.

Overall, the procedures involved in this study carry minimal risks to the
participants, are conducted by trained and licensed professionals, adhering to
local standards to ensure patient safety and minimize any potential risks.