This is a prospective and explorative clinical study performed at one centre. Objective: The objective of this study is to assess the clinical efficacy of pulmonary vein isolation using the Arctic Front Advance cryoballoon in patients with longstanding persistent atrial fibrillation (AF) at one year follow up.~44 subjects will be enrolled. Clinical sites: Arrhythmia centre in Uppsala University Hospital, Uppsala Sweden.~Subject population: Patients with longstanding persistent AF, with continuous AF of longer duration than one year, who have not previously undergone an AF ablation procedure, and who have symptoms related to AF corresponding to at least EHRA score 2, will be studied. Atrial fibrillation should be confirmed on at least 2 consecutive ECG recordings during the past one year supporting the presence of AF for at least one year. Patients should have failed at least a betablocker or class I or III antiarrhythmic drug.~In order to exclude permanent AF patients, an electrical cardioversion with conversion to sinus rhythm maintained for at least one hour, is required.~Excluded patients are those with congestive heart failure with New York Heart Association (NYHA) class 3 or more, left ventricular ejection fraction (LVEF) < 40%, left atrial diameter (LA) ≥ 60 mm, significant valvular disease or planned cardiac intervention within the next 12 months, and conventional medical contraindications for AF ablation procedures.~Pulmonary vein isolation: Pulmonary vein isolation (PVI) will be performed using the Arctic Front Advance cryoballoon ablation catheter. Acute procedural success is defined as electrical isolation of all pulmonary veins assessed by entrance and exit block, including 20 minutes waiting time and the use of the provocative agent adenosine to screen for early recurrence of PV conduction.~Design of the study: Patients will be screened with echocardiography and response to electrical cardioversion. Following conversion to sinus rhythm, amiodarone will be initiated in order to maintain sinus rhythm.~After cryoballoon ablation of all pulmonary veins, PV conduction block will be assessed by a circular mapping catheter, including waiting time and provocative agents. All patients will be subject to electro anatomical voltage mapping during sinus rhythm for demonstration of the extent of atrial myocardial lesions after ablation. Biomarkers including nTproBNP and troponin I, reflecting myocardial strain and destruction, will be collected at baseline and at different time points after the procedure.~Patients will be followed every third month up to one year after the ablation procedure. Amiodarone will be withdrawn one month after the ablation procedure.~Arrhythmia monitoring during follow up will be performed by a 7 day Holter monitoring every third month at 6, 9 and 12 months follow up, including a 12 lead ECG.~A transthoracic echocardiography will be repeated at 12 months follow up to assess LA volume and contractility. Symptoms, EHRA score, and quality of life (QoL) will be evaluated. Predictive variables for successful outcome/AF recurrence will be analysed.~All patients will be reinvestigated for assessment of PV re-conduction using a circular mapping catheter, irrespective of symptoms. Patients with symptomatic recurrence requiring a redo ablation procedure will be re-studied after 8-12 months while asymptomatic patients will be studied at 12 months follow up.~Primary end-point:~Clinical success defined as~Freedom from AF related symptoms, off or on previously ineffective antiarrhythmic drugs irrespective of the presence of asymptomatic AF on Holter. AF may be either absent or paroxysmal in nature, or~Presence of AF related symptoms, off or on previously ineffective antiarrhythmic drugs, but with significant symptomatic improvement to the extent that a redo procedure or a novel previously not tested antiarrhythmic drug is not desired as declared by the patient on a symptom questionnaire. Atrial fibrillation may be either absent or paroxysmal as recorded on Holter or ECG tracings after 1 or 2 procedures at 12 months.~Secondary end-points:~Complete freedom from AF without antiarrhythmic drugs at 6 and 12 months after 1-2 ablation procedures according to 7 day Holter and ECG.~Rhythm (% of subjects in sinus rhythm, paroxysmal AF and persistent AF) at 12 months.~AF burden on 7 day Holter at 12 months.~AF profile~Assess whether PVI is crucial for elimination of AF in patients with longstanding persistent AF. Correlation between freedom from AF/recurrence and PV isolation/re-conduction at repeat electrophysiological study.~Systemic blood pressure.~Quality of Life determined by standardized questionnaires (SF 36, with all domains and time-points and EQ 5D).~Symptoms (Symptoms Severity Questionnaire and EHRA Symptom Classification).~Incidence, intensity and relationship of Adverse Events.~Left and right atrial size and function (sinus rhythm) (echocardiography corrected for Body Surface area, dPdT) prior to and after ablation at 12 months.~Biomarkers including nTproBNP and troponin I, reflecting myocardial strain and destruction, will be collected at baseline and at different time points after the procedure. A biomarker reflecting fibrosis and brain damage will be analysed.~Extent of scar tissue as indicated by LA voltage mapping at baseline and extent of electrical silence around PV postablation.~A subgroup analysis will determine whether sinus rhythm obtained by AF ablation is superior AF with regard to all secondary endpoints including QoL, Symptoms, cardiovascular hospitalizations, safety, biomarkers, left atrial size and function, at 12 months.~Prediction of freedom from AF by risk variables including LA volume, LA contractility (strain rate), LA intracardiac pressures and dpdt, Atrial amplitude analysis during AF prior ablation, extent of scar tissue as assessed by a voltage mapping at baseline during sinus rhythm, biomarkers, and demographic variables (AF duration, hypertension, ischemic heart disease, diabetes and CHADS2VASscore).~Catheter related complications.~Cardiovascular hospitalization~Health economics
Prospective and explorative clinical study. The objective is to assess the clinical efficacy of pulmonary vein isolation using the Arctic Front Advance cryoballoon in patients with longstanding persistent atrial fibrillation (AF) at one year follow up.~44 subjects will be enrolled. Patients with longstanding persistent AF, with continuous AF duration longer than one year, who have not previously undergone an AF ablation procedure, and have symptoms related to AF corresponding to at least European Heart Rhythm Association (EHRA) score 2, will be studied. Patients should have failed at least one betablocker or class I or III antiarrhythmic drug.~Excluded are those with congestive heart failure with New York Heart Association (NYHA) class 3 or more, left ventricular ejection fraction < 40%, left atrial diameter ≥ 60 mm, significant valvular disease or planned cardiac intervention within next 12 months, and conventional contraindications for AF ablation procedures.~Patients will be screened with echocardiography and response to electrical cardioversion. Following conversion to sinus rhythm, amiodarone will be initiated to maintain sinus rhythm. Pulmonary vein isolation will be performed using the Arctic Front Advance cryoballoon ablation catheter. Pulmonary vein conduction block will be assessed by a circular mapping catheter.~All patients will be subject to electroanatomical voltage mapping during sinus rhythm for demonstration of extent of atrial myocardial lesions after ablation.~Patients will be followed every third month up to one year after the ablation procedure. Arrhythmia monitoring during follow up will be performed by 7 day Holter monitoring at 6, 9 and 12 months follow up, including a 12 lead ECG. 12 months follow up for symptoms, EHRA score, and quality of life. Patients with symptomatic recurrence requiring a redo ablation procedure will be re-studied after 8-12 months while asymptomatic patients will be studied at 12 months follow up.~Primary end-Point is Clinical success based on symptoms and presence of AF. Secondary end-Points include freedom from AF without antiarrhythmic drugs at 6 and 12 months according to 7 day Holter and ECG, Rhythm, AF burden, AF profile, Quality of Life, Symptoms, Adverse Events, atrial size and function, Biomarkers, extent of scar tissue, predictive factors of freedom from AF, complications, hospitalization and Health economics.