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

Heart Failure Clinical Trial

— CASTLE-AF  

Official title:

Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00643188
• Other study ID #: EP020
• Status: Completed
• Phase: Phase 4
• First received: February 22, 2008
• Last updated: May 17, 2017
• Start date: January 2008
• Est. completion date: March 2017

Study information

• Verified date: May 2017
• Source: Biotronik SE & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 398
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

Procedure:
• Radiofrequency ablation
Radiofrequency ablation of atrial fibrillation

Other:
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Royal Brisbane and Women's Hospital	Herston
Austria	A. ö. Krankenhaus der Elisabethinen Linz	Linz
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Germany	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
Hungary	Semmelweis Medical University	Budapest
Hungary	The Debrecen University of Medicine	Debrecen
Netherlands	Antonius Ziekenhuis	Nieuwegein
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Isala Klinieken	Zwolle
Poland	National Institute of Cardiology	Warszawa
Russian Federation	HRD Surgical Department; Federal Centre of Cardiovascular Surgery	Krasnoyarsk
Russian Federation	N.S.B.R.I. of Circulation Pathology	Novosibirsk
Russian Federation	Arrhythmology Department; Federal Heart Blood and Endocrinology Center n.a. V. A. Almazov	Saint Petersburg
Russian Federation	FSBI Research Institute of Cardiology, Siberian Branch of RAMS	Tomsk
United Kingdom	The Heart Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Biotronik SE & Co. KG

Countries where clinical trial is conducted

Australia,  Austria,  Germany,  Hungary,  Netherlands,  Poland,  Russian Federation,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality or worsening heart failure requiring unplanned hospitalization		7 years
Secondary	All-cause mortality Cardiovascular mortality Unplanned hospitalization due to cardiovascular reason Worsening heart failure requiring unplanned hospitalization Cerebrovascular accidents Left ventricular function Exercise tolerance Quality of life		7 years

External Links

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