Clinical trial NCT00643188: Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF
Official title: Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Heart Failure
Keywords: Atrial fibrillation
Ablation
Heart failure
Home Monitoring
Lead sponsor: Biotronik SE & Co. KG
Sponsor class: INDUSTRY
First posted: 2008-03-26
Enrollment: 398
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: All-cause mortality or worsening heart failure requiring unplanned hospitalization
timeFrame: 7 years
Secondary outcomes:
measure: 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
timeFrame: 7 years
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Linz
country: Austria
facility: A. ö. Krankenhaus der Elisabethinen Linz
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité Campus Mitte
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Franz-Volhard-Klinik, Universitätsklinikum Charité
city: Berlin
country: Germany
facility: Vivantes-Klinikum am Urban
city: Bielefeld
country: Germany
facility: Städtische Kliniken Bielefeld
city: Bonn
country: Germany
facility: St. Marien Hospital
city: Bremen
country: Germany
facility: Zentralkrankenhaus Links der Weser, Siebels & Langes Partnerschaft
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Düsseldorf
country: Germany
facility: Evangelisches Krankenhaus Düsseldorf
city: Frankfurt am Main
country: Germany
facility: Kardiocentrum Frankfurt an der Klinik Rotes Kreuz
city: Greifswald
country: Germany
facility: Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald
city: Landshut
country: Germany
facility: Krankenhaus Landshut-Achdorf
city: Lüdenscheid
country: Germany
facility: Klinikum Lüdenscheid
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: Paderborn
country: Germany
facility: St. Vincenz-Krankenhaus
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock
city: Budapest
country: Hungary
facility: Semmelweis Medical University
city: Debrecen
country: Hungary
facility: The Debrecen University of Medicine
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Warszawa
country: Poland
facility: National Institute of Cardiology
city: Krasnoyarsk
country: Russian Federation
facility: HRD Surgical Department; Federal Centre of Cardiovascular Surgery
city: Novosibirsk
country: Russian Federation
facility: N.S.B.R.I. of Circulation Pathology
city: Saint Petersburg
country: Russian Federation
facility: Arrhythmology Department; Federal Heart Blood and Endocrinology Center n.a. V. A. Almazov
city: Tomsk
country: Russian Federation
facility: FSBI Research Institute of Cardiology, Siberian Branch of RAMS
city: London
country: United Kingdom
facility: The Heart Hospital
Study officials:
affiliation: Klinikum Coburg, Germany
name: Johannes Brachmann, Prof. Dr.
role: STUDY_CHAIR
affiliation: Division of Cardiology, University of Utah Health Sciences Cente, Salt Lake City, Utah, United States
name: Nassir F. Marrouche, Dr.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.