Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure

Heart Failure Clinical Trial

— ARC-HF  

Official title:

A Randomised Trial to Assess Catheter Ablation Versus Rate-Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00878384
• Other study ID #: 2008CI008B
• Status: Completed
• Phase: N/A
• First received: April 7, 2009
• Last updated: July 11, 2012
• Start date: April 2009
• Est. completion date: July 2012

Study information

• Verified date: July 2012
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

It is still uncertain what the best treatment is for patients who have both atrial fibrillation (AF) and heart failure. The aim of the study is to help identify the optimal treatment for patients with these two significant medical conditions. This will be performed by comparing two alternative strategies for AF management: catheter ablation (to restore normal rhythm) and medical therapy (to control heart rate, but not aiming ro restore normal rhythm). After random assignment, the effect of each strategy will be assessed by looking for changes in exercise capacity, symptoms, heart pump function, and quality of life during 12 months of follow-up.

Description:

Currently available evidence suggests that occurrence of AF in patients with heart failure (HF) leads to a decline in exercise tolerance, worsened quality of life, increased hospitalisation, and in many studies an increase in mortality. These may be explained by the haemodynamic effects of AF i.e. reduction in functional cardiac output due to inappropriate heart rates, irregularity, and loss of atrial contraction, plus the risk of thromboembolism.

Evidence from large clinical studies has shown that patients with heart failure fare better if sinus rhythm can be restored, but on the contrary a 'rhythm control' strategy (as intention to treat) of cardioversion or antiarrhythmic drugs to achieve sinus rhythm has not been shown to be superior to the strategy of rate control. These apparently contradictory findings might be explained by the poor efficacy and side effects associated with current rhythm control strategies, or could reflect that AF is merely a passive marker of underlying disease severity. However, many studies would point to the former, and it might be hypothesised that the theoretical benefits of sinus rhythm could be seen for real in clinical practice if a superior rhythm-control strategy was used.

Catheter ablation, a relatively new treatment for atrial fibrillation, has been shown to be feasible in a non-randomised heart failure patient cohort, with markers suggesting improvement of cardiac function.

This prospective clinical trial will enrol HF patients on optimal therapy, with documented persistent AF, and compare the strategies of catheter-ablation and medical rate control in a 1:1 randomised fashion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria:

• Age = 18 years, < 80years

• NYHA II-IV symptoms

• Impairment of left ventricular systolic function (left ventricular ejection fraction estimated as = 35% by radionuclide ventriculography)

• Documented AF lasting for at least 7 days (persistent or permanent AF)

Exclusion criteria:

• CRT or ICD device implanted in the previous 6 months

• AV nodal ablation within previous 3 months

• Prior AV nodal ablation or complete heart block with a single chamber pacemaker

• Contraindication to anticoagulation

• Persistent thrombus in the left atrium despite anticoagulation

• Active malignancy

• Cerebrovascular accident within the previous 6 months

• Reversible causes of AF including thyroid disorders, alcohol, recent surgery

• Reversible causes of heart failure including acute myocarditis or alcohol

• Cardiac events including myocardial infarction (MI), percutaneous coronary intervention (PCI), valve or coronary bypass surgery within the previous 3 months

• Prior AF ablation procedure

• Previous heart transplant, or on urgent heart transplant waiting list

• Severe neuro-muscular disease

• Creatinine clearance <30 ml/min

• Serum bilirubin >50 micromol/L

• Active participation in another research study

• Unable to understand and comply with protocol or give written informed consent

• Body mass index >35 (kg/m2)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

Drug:
• Medication to control ventricular rate in AF
Standard pharmacologic rate control. Current therapy will be adjusted to achieve rate-control targets of <80bpm and <110bpm on exercise (6 minute walk). Where necessary, additional medication will be given as per standard practice (digoxin or beta-blocker). Typical does: Digoxin 62.5-250mcg o.d. ; Bisoprolol 1.25-20mg o.d.; Carvedilol 3.125-50mg b.d. ; Nebivolol 1.25-10mg o.d.

Procedure:
• Catheter Ablation for Persistent Atrial Fibrillation
Radiofrequency catheter ablation, which may include pulmonary vein isolation, atrial substrate modification, and/or linear ablation.

Locations

Country	Name	City	State
United Kingdom	Royal Brompton & Harefield NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG; AFFIRM Investigators. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004 Mar 30;109(12):1509-13. Epub 2004 Mar 8. — View Citation

Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998 Sep;32(3):695-703. — View Citation

Hagens VE, Crijns HJ, Van Veldhuisen DJ, Van Den Berg MP, Rienstra M, Ranchor AV, Bosker HA, Kamp O, Tijssen JG, Veeger NJ, Van Gelder IC; RAte Control versus Electrical cardioversion for persistent atrial fibrillation study group. Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study. Am Heart J. 2005 Jun;149(6):1106-11. — View Citation

Hsu LF, Jaïs P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M, Pasquié JL, Scavée C, Bordachar P, Clémenty J, Haïssaguerre M. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med. 2004 Dec 2;351(23):2373-83. — View Citation

Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. Circulation. 1991 Jul;84(1):40-8. — View Citation

Pedersen OD, Brendorp B, Elming H, Pehrson S, Køber L, Torp-Pedersen C. Does conversion and prevention of atrial fibrillation enhance survival in patients with left ventricular dysfunction? Evidence from the Danish Investigations of Arrhythmia and Mortality ON Dofetilide/(DIAMOND) study. Card Electrophysiol Rev. 2003 Sep;7(3):220-4. — View Citation

Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O'Hara G, Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B, Waldo AL; Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19;358(25):2667-77. doi: 10.1056/NEJMoa0708789. — View Citation

Swedberg K, Olsson LG, Charlesworth A, Cleland J, Hanrath P, Komajda M, Metra M, Torp-Pedersen C, Poole-Wilson P. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J. 2005 Jul;26(13):1303-8. Epub 2005 Mar 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak oxygen consumption at cardiopulmonary exercise test		12 months	No
Secondary	Left ventricular ejection fraction		12 months	No
Secondary	Quality of Life score		3, 6 and 12 months	No
Secondary	6 minute walk distance		3, 6 and 12 months	No
Secondary	Level of plasma neurohormones (including BNP)		3, 6 and 12 months	No
Secondary	Freedom from AF		3, 6 and 12 months	No