Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF

NCT ID: NCT00643188

Last Updated: 2017-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 398 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2017-03-31

Brief Summary

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The incidence and prevalence of AF increase exponentially with increasing age and AF is associated with higher mortality, more frequent hospitalization, and lower quality of life. Furthermore, AF is often associated with heart failure. The majority of AF is initiated by ectopic foci found primarily in the pulmonary veins. It was shown that catheter ablation of those veins could eliminate episodes of AF. In patients with heart failure, catheter ablation could improve cardiac function, symptoms and quality of life. It remains still unknown whether AF ablation is more effective than conventional treatment in terms of mortality and morbidity.

Detailed Description

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice; its incidence and prevalence increase exponentially with increasing age and it is associated with increased mortality, more frequent hospitalization, and decreased quality of life.

An initial approach to the cure of patients suffering from AF was surgical intervention with the Maze procedure, which involved the creation of linear lesions in the atria to break the re-entrant wavefronts responsible for maintenance of AF. Subsequently, less invasive procedures have been developed to achieve the same results. One of them is catheter based radio frequency ablation, in which a catheter is placed in the heart percutaneously, followed by application of electrical energy to the target regions, thereby creating a permanent lesion.

The origin of AF is often localized in the pulmonary veins (PVs); therefore one common approach is to ablate them in order to electrically isolate them from the left atrium (LA). Several strategies have been developed, such as linear, segmental, circumferential, and double-lasso.

Additionally, other anatomical regions such as the right atrium (RA), superior vena cava (SVC), and coronary sinus (CS) can be ablated in order to eliminate non-PV drivers of AF.

Heart failure (HF) is frequently a chronic and lethal condition, causing substantial morbidity and, after initial diagnosis, results in mortality rates which come close to or exceed those of many malignancies.

Both AF and HF have a significant impact on the health care expenditures. The two diseases often coexist, there is a complex interaction between them: many of the processes that predispose to HF, such as hypertension, diabetes, coronary artery disease, and valvular heart disease, are also risk factors for the development of AF. Similarly, many of the echocardiographic findings that are common in patients with HF, including LA enlargement, increased left ventricular (LV) wall thickness, and reduced LV fractional shortening, predispose patients in the development of AF.

In small groups of patients suffering from HF and AF, radio frequency ablation has been performed; the restoration of sinus rhythm resulted in the improvement of quality of life, exercise performance, and cardiac parameters like ejection fraction and fractional shortening. It is still unknown if such therapy is also effective in reducing mortality and morbidity.

CASTLE-AF is a prospective, unblinded, randomized, multicenter study whose aim is to compare the effect of radio frequency catheter-based ablation on mortality and morbidity with that of conventional treatment in HF subjects with AF. About 420 patients with LV dysfunction (ejection fraction ≤ 35%) and New York Heart Association (NYHA) class ≥ II, already implanted with a dual chamber implantable cardioverter defibrillator (ICD) with Home Monitoring® capabilities, will be enrolled and randomized 1:1 to undergo either AF ablation or standard treatment as indicated in the American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology (ESC) 2006 guidelines for the management of patients with AF. In addition to planned and unplanned visits, the ablated patients will be constantly monitored remotely via Home Monitoring®, in order to detect any recurrences of AF episodes, even if non-symptomatic or short in duration, during an observational period of minimum 3 years for each patient.

Conditions

Atrial Fibrillation; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Radiofrequency ablation of atrial fibrillation:

Subjects assigned to the catheter AF ablation strategy will undergo ablation within 48 hours after baseline evaluation. The aim of the procedure is to achieve isolation of all Pulmonary Veins (PVs) and to restore sinus rhythm. Only radiofrequency catheter based AF ablation is permitted; other methods, like cryoablation, ultrasound and laser, are not permitted in this study.

Before ablation, a transesophageal echocardiogram must be performed in order to rule out presence of atrial thrombi.

Anticoagulation should be initiated, or continued, for at least six months post ablation. Six months after successful ablation and in absence of any recurrence of AF, antiarrhythmic drugs should be discontinued.

Group Type: EXPERIMENTAL

Radiofrequency ablation

Intervention Type: PROCEDURE

Radiofrequency ablation of atrial fibrillation

2

Conventional treatment:

Subjects assigned to the conventional treatment strategy will be treated according to current guidelines for the management of patients with chronic heart failure and/or atrial fibrillation. Efforts to maintain sinus rhythm in this study arm are recommended.

Anticoagulation will be initiated, if not already started, and maintained throughout the study according to current guidelines.

Group Type: ACTIVE_COMPARATOR

Conventional treatment

Intervention Type: OTHER

The best medical treatment according to the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult and the ACC/AHA/ESC 2006 Guidelines for Management of Patients with Atrial Fibrillation.

Interventions

Radiofrequency ablation

Radiofrequency ablation of atrial fibrillation

Intervention Type: PROCEDURE

Conventional treatment

The best medical treatment according to the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult and the ACC/AHA/ESC 2006 Guidelines for Management of Patients with Atrial Fibrillation.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Symptomatic paroxysmal or persistent atrial fibrillation
• Failure or intolerance of antiarrhythmic drug therapy or unwillingness to take antiarrhythmic drugs
• Left Ventricular Ejection Fraction <= 35%
• NYHA >= II
• ICD for primary or secondary prevention with atrial sensing capabilities or Cardiac Resynchronization Therapy plus Defibrillator (CRT-D) device, both with Home Monitoring® technology already implanted
• Patient is willing and able to comply with the protocol and has written informed consent
• Age >= 18 years

Exclusion Criteria

• Contraindication for chronic anticoagulation therapy and heparin
• Documented left atrial diameter > 6 cm
• Previous left heart ablation procedure for atrial fibrillation
• Acute coronary syndrome, cardiac surgery, angioplasty or stroke within 2 months prior to enrollment
• Untreated hypothyroidism or hyperthyroidism
• Enrollment in another investigational drug or device study
• Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertility age
• Mental or physical inability to take part in the study
• Listed for heart transplant
• Cardiac assist device implanted
• Planned cardiovascular intervention
• Life expectancy ≤ 12 months
• Uncontrolled hypertension
• Requirement for dialysis due to terminal renal failure
• Participation in another telemonitoring concept

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biotronik SE & Co. KG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johannes Brachmann, Prof. Dr.

Role: STUDY_CHAIR

Klinikum Coburg, Germany

Nassir F. Marrouche, Dr.

Role: STUDY_CHAIR

Division of Cardiology, University of Utah Health Sciences Cente, Salt Lake City, Utah, United States

Locations

Royal Adelaide Hospital

Adelaide, , Australia

Royal Brisbane and Women's Hospital

Herston, , Australia

A. ö. Krankenhaus der Elisabethinen Linz

Linz, , Austria

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Herz- und Diabeteszentrum Nordrhein-Westfalen

Bad Oeynhausen, , Germany

Charité Campus Mitte

Berlin, , Germany

Charité Campus Virchow-Klinikum

Berlin, , Germany

Franz-Volhard-Klinik, Universitätsklinikum Charité

Berlin, , Germany

Vivantes-Klinikum am Urban

Berlin, , Germany

Städtische Kliniken Bielefeld

Bielefeld, , Germany

St. Marien Hospital

Bonn, , Germany

Zentralkrankenhaus Links der Weser, Siebels & Langes Partnerschaft

Bremen, , Germany

Klinikum Coburg

Coburg, , Germany

Evangelisches Krankenhaus Düsseldorf

Düsseldorf, , Germany

Kardiocentrum Frankfurt an der Klinik Rotes Kreuz

Frankfurt am Main, , Germany

Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald

Greifswald, , Germany

Krankenhaus Landshut-Achdorf

Landshut, , Germany

Klinikum Lüdenscheid

Lüdenscheid, , Germany

Deutsches Herzzentrum München

München, , Germany

St. Vincenz-Krankenhaus

Paderborn, , Germany

Universitätsklinikum Rostock

Rostock, , Germany

Semmelweis Medical University

Budapest, , Hungary

The Debrecen University of Medicine

Debrecen, , Hungary

Antonius Ziekenhuis

Nieuwegein, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

National Institute of Cardiology

Warsaw, , Poland

HRD Surgical Department; Federal Centre of Cardiovascular Surgery

Krasnoyarsk, , Russia

N.S.B.R.I. of Circulation Pathology

Novosibirsk, , Russia

Arrhythmology Department; Federal Heart Blood and Endocrinology Center n.a. V. A. Almazov

Saint Petersburg, , Russia

FSBI Research Institute of Cardiology, Siberian Branch of RAMS

Tomsk, , Russia

The Heart Hospital

London, , United Kingdom

Countries

Australia; Austria; Germany; Hungary; Netherlands; Poland; Russia; United Kingdom

References

Marrouche NF, Brachmann J; CASTLE-AF Steering Committee. Catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation (CASTLE-AF) - study design. Pacing Clin Electrophysiol. 2009 Aug;32(8):987-94. doi: 10.1111/j.1540-8159.2009.02428.x.

Reference Type: BACKGROUND

PMID: 19659616 (View on PubMed)

Brachmann J, Sohns C, Andresen D, Siebels J, Sehner S, Boersma L, Merkely B, Pokushalov E, Sanders P, Schunkert H, Bansch D, Dagher L, Zhao Y, Mahnkopf C, Wegscheider K, Marrouche NF. Atrial Fibrillation Burden and Clinical Outcomes in Heart Failure: The CASTLE-AF Trial. JACC Clin Electrophysiol. 2021 May;7(5):594-603. doi: 10.1016/j.jacep.2020.11.021. Epub 2021 Feb 24.

Reference Type: DERIVED

PMID: 33640355 (View on PubMed)

Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, Merkely B, Pokushalov E, Sanders P, Proff J, Schunkert H, Christ H, Vogt J, Bansch D; CASTLE-AF Investigators. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med. 2018 Feb 1;378(5):417-427. doi: 10.1056/NEJMoa1707855.

Reference Type: DERIVED

PMID: 29385358 (View on PubMed)

Related Links

http://www.castle-af.org

Click here for more information about this study: CASTLE-AF

Other Identifiers

EP020

Identifier Type: -

Identifier Source: org_study_id