Clinical trial NCT01553045: Reasons for Variations in Health Related Quality of Life and Symptom Burden in Patients With Atrial Fibrillation
Official title: Observational Study of the Variation in Health-related Quality of Life and Symptom Burden in Patients Accepted for Catheter Ablation of Atrial Fibrillation in Relation to Biomarkers, Intracardiac Pressures and Echocardiography.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Arrhythmias, Cardiac
Heart Failure, Systolic
Atrial Fibrillation
Keywords: symptom burden
atrial fibrillation
biomarkers
intracardiac pressures
Lead sponsor: University Hospital, Linkoeping
Sponsor class: OTHER
First posted: 2012-03-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referred for catheter ablation of atrial fibrillation for the first time.

Brief summary: Atrial fibrillation is the most common cardiac arrhythmia. There is a large variation in symptoms; from almost none to severe but the reason for this is unclear.

The investigators aim to find correlations between symptom burden and intracardiac pressure, biomarkers and findings with echocardiography in order to find alternative means of treatment.

It is even intended to study the neurohormonal activation directly after the atrial fibrillation (AF) initiation in patients eligible for AF radiofrequency ablation.

Detailed description: Atrial fibrillation (AF) is the most common cardiac arrhythmia and more than 1 % of the population suffers from AF, it is an independent risk factor for ischemic stroke One major unresolved issue concerning AF is the large variety in symptoms. In some AF is diagnosed accidentally while in others symptoms are severe and disabling.

It is known that B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) is stored in nodules in the atrial and ventricular myocytes and is produced in response to increased 'afterload' and 'preload' to restore and maintain cardiovascular homeostasis. Vasopressin (AVP), a non-cardiac plasma marker of cardiovascular disease, is released from the neurohypophysis in response to changes in plasma osmolality and is involved in osmoregulation and cardiovascular homeostasis. Adrenomodullin originates primarily in endothelial cells where cellular stress, ischaemia and hypoxia result in an increased production.

It is well-known that the concentrations of the natriuretic peptides are elevated in patients with AF and that the plasma concentrations decreased after conversion to sinus rhythm (SR). Yet their reaction when AF initiates is totally unknown. Moreover the role of ADM and AVP-hormonal system has not been researched in this category of patients.

Patients scheduled for catheter ablation of AF for the first time will be included; all with symptoms varying from moderate to severe. Using four health related quality of life forms the impact of AF on symptoms will be evaluated. Patients will be investigated with echocardiography, invasive hemodynamics and measurement of the levels of peptide indicators of heart failure and/or impact on myocardial function. Patients will also be categorized according to metabolic profile.

The information on this subject is scarce. Hemodynamic data is old and not correlated to symptoms. Effective and validated means of measuring health related quality of life including symptoms burden are relatively new tools. The aim is to find correlations between the impact on health related quality of life and parameters from echocardiographic measurements, from analysis of biomarkers (peptides) and from analysis of the metabolic profile.

In order to study the response of these four different neurohormonal systems (represented by NT-proBNP, MR-proANP, MR-proADM, copeptin) after the initiation of AF, a randomized interventional clinical sub-study is to be performed where the eligible population of SMURF main study can be randomized to AF induction or to control if freedom from AF is confirmed with thumb-ecg during the last 4 days before ablation. 45 patients are to be included to the sub-study with 2:1 allocation ratio with simple randomization.

If such correlations can be found alternate means for symptoms relief in AF patients can be identified and further ahead implemented in general health care.

The sub-study can give us a better insight on the AF initiation and the activation of different neurohormonal systems, an areas which is not well investigated.

Eligibility criteria: Inclusion Criteria:

* Persistent or paroxysmal atrial fibrillation
* Symptoms of atrial fibrillation
* Referred for catheter ablation

Sub-study:

Same inclusion criteria as the main study plus

-Freedom from arrhythmia the last four days before radiofrequency ablation.

Exclusion Criteria:

* Previous ablation attempts (surgical or catheter ablation)
* Unstable coronary disease
* Heart failure (NYHA III-IV)

Sub-study:

Same exclusion criteria as the main study

Primary outcomes:
measure: Symptom burden vs. peptide markers for heart failure
timeFrame: 3 years
measure: Sub-study primary outcome: Levels of four biomarkers in relation to heart rhythm
timeFrame: 3 years
Secondary outcomes:
measure: Levels of NT-proBNP and MR-proANP in different sites of the heart and the effect of radiofrequency ablation in relation to heart rhythm
timeFrame: 3 years
measure: Levels of copeptin and MR-proADM in different sites of the heart and the effect of radiofrequency ablation
timeFrame: 3 years
measure: The relation between left atrial function and neurohormonal activation in patients with atrial fibrillation eligible for radio frequency ablation
timeFrame: 3 years
measure: The effect of radiofrequency ablation on the left atrial and left atrial appendix function
timeFrame: 3 years
measure: Alcohol consumption in a atrial fibrillation population undergoing radio frequency ablation (RFA), the connection between alcohol consumption and quality of life and arrhythmia freedom after RFA
timeFrame: 3 years
measure: Which factors influence the quality of life in patients with atrial fibrillation (AF) undergoing ablation. Do patients with more symptoms have a greater activation of neurohormonal systems and increase of intracardiac pressures after the initiation of AF
timeFrame: 3 years
Other outcomes:
Locations:
city: Linkoeping
country: Sweden
facility: Dept of Cardiology, University Hospital
Study officials:
affiliation: IMH, Dept of Medical and Health Sciences, Linkoping University
name: Anna Stromberg, Prof, R.N.
role: PRINCIPAL_INVESTIGATOR
affiliation: IMH, Department of Medical and Health Sciences, Linkoping University
name: Urban Alehagen, Ass prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IMH, Department of Medical and Health Sciences, Linkoping University
name: Fredrik Nystrom, Prof, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: IMH, Department of Medical and Health Sciences, Linkoping University
name: Eva Nylander, Prof, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Charitakis E, Karlsson LO, Papageorgiou JM, Walfridsson U, Carlhall CJ. Echocardiographic and Biochemical Factors Predicting Arrhythmia Recurrence After Catheter Ablation of Atrial Fibrillation-An Observational Study. Front Physiol. 2019 Oct 2;10:1215. doi: 10.3389/fphys.2019.01215. eCollection 2019.
citation: Charitakis E, Barmano N, Walfridsson U, Walfridsson H. Factors Predicting Arrhythmia-Related Symptoms and Health-Related Quality of Life in Patients Referred for Radiofrequency Ablation of Atrial Fibrillation: An Observational Study (the SMURF Study). JACC Clin Electrophysiol. 2017 May;3(5):494-502. doi: 10.1016/j.jacep.2016.12.004. Epub 2017 Mar 1.
citation: Charitakis E, Walfridsson H, Nylander E, Alehagen U. Neurohormonal Activation After Atrial Fibrillation Initiation in Patients Eligible for Catheter Ablation: A Randomized Controlled Study. J Am Heart Assoc. 2016 Dec 12;5(12):e003957. doi: 10.1161/JAHA.116.003957.
citation: Charitakis E, Walfridsson H, Alehagen U. Short-Term Influence of Radiofrequency Ablation on NT-proBNP, MR-proANP, Copeptin, and MR-proADM in Patients With Atrial Fibrillation: Data From the Observational SMURF Study. J Am Heart Assoc. 2016 Sep 15;5(9):e003557. doi: 10.1161/JAHA.116.003557.
citation: Charitakis E, Walfridsson U, Nystrom F, Nylander E, Stromberg A, Alehagen U, Walfridsson H. Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation (SMURF): a protocol for an observational study with a randomised interventional component. BMJ Open. 2015 Dec 21;5(12):e008723. doi: 10.1136/bmjopen-2015-008723.