Persistent Atrial FibrillationPhase 4AFARC-LVFNCT02509754
Atrial Fibrillation Ablation Compared to Rate Control Strategy in Patients With Impaired Left Ventricular Function
A Phase 4 study testing Atrial fibrillation catheter ablation in people with Persistent Atrial Fibrillation and Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction, run by University of Turin, Italy.
Trial summary
Atrial fibrillation (AF) and congestive heart failure (CHF) are two epidemics that share several physiopathological links. CHF patients present a significantly increased risk of developing AF and the related detrimental hemodynamic effects are even more relevant than in patients without CHF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Persistent Atrial Fibrillation, Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction
- What is being tested?
- Atrial fibrillation catheter ablation
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recent (no longer than 6 months) diagnosis of congestive heart failure, defined as left ventricular ejection fraction lower or equal than 35% along with the presence of symptoms of heart failure, with a NYHA class II, III or ambulatory IV;
- Optimal medical therapy from at least 3 months (including a beta-blocker, an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) and, in NYHA III and IV patients, spironolactone);
- Persistent atrial fibrillation (at least 3 months or, alternatively, a minimum of two previous episodes lasting longer than 7 days);
- Refractory to at least one, or intolerant to, antiarrhythmic drug/s;
- Must be able to provide written informed consent.
Who cannot join
- Reversible causes of atrial fibrillation or congestive heart failure;
- Permanent or long-standing persistent atrial fibrillation (lasting more than 1 year);
- Previous surgical or transcatheter AF ablation;
- Previously implanted CRT with or without concomitant AV node ablation;
- QRS duration above 150 msec or above 120 msec in the presence of complete left bundle branch block (class IIa indication for CRT implantation);
- Life expectancy of one year or less;
Show all 12Show fewer
- High likelihood of undergoing cardiac transplantation within the next year;
- Contraindication to anticoagulant therapy;
- Documented intraatrial thrombus, tumor, or other abnormality that precludes catheter introduction and manipulation;
- Inability to perform a 6-minute walking test;
- Absence of optimal medical therapy as previously described;
- Cardiac surgery, myocardial infarction or percutaneous coronary intervention within the previous 3 months.
Trial locations and contacts
No sites are listed yet.
Mario Matta, M.D. contact
About this study
Official title: Atrial Fibrillation Ablation Compared to Rate Control Strategy in Patients With Recently Diagnosed Impaired Left Ventricular Function: a Multicenter, Randomized Controlled Trial
Atrial fibrillation (AF) and congestive heart failure (CHF) are two epidemics that share several physiopathological links. CHF patients present a significantly increased risk of developing AF and the related detrimental hemodynamic effects are even more relevant than in patients without CHF.
Within CHF patients rate control is the most widely used strategy to manage AF, having proved non-inferior to rhythm control strategies. However, by this strategy, the hemodynamic effects of AF persist, not contrasting the natural evolution towards progressive left ventricular (LV) function, cardiac output , and symptoms worsening. Rhythm control strategy, instead, has shown, in the general population, advantages over rate control concerning survival, quality of life and thromboembolic events. The main limitation is that antiarrhythmic therapy used to achieve this goal has several side effects, and that transcatheter AF ablation has been assessed only in modest sample size studies.
Read more
Available literature focusing on a direct comparison between two specific management strategies in patients with CHF and AF is limited to a small randomized study comparing pulmonary veins isolation to AV node ablation and biventricular PM implantation (PABA-CHF study). Additional indirect evidences may derive from meta-analyses of observational studies.
The investigators therefore designed this multicenter, randomized controlled trial aiming to assess if, in recently diagnosed (less than 6 months) and optimally treated CHF patients with impaired LV function, AF catheter ablation is effective in improving LV function and clinical functional class, potentially driving to a reduction of device implantations (ICD/CRTs).
Read the detailed description
Atrial fibrillation (AF) is the most common arrhythmia among the general population. Its prevalence increases with advanced age but also with the presence of structural heart disease. In particular patients suffering from congestive heart failure (CHF) with low left ventricular (LV) ejection fraction present a significantly increased risk of developing AF and its detrimental hemodynamic effects, due to the loss of atrial contraction, and fast and irregular beats, are an even more relevant compared to patients without CHF.
In CHF patients rate control is the most widely used strategy to manage AF; in fact, it has proved non-inferior to rhythm control strategies concerning survival rates . However, adequate ventricular rate is difficult to achieve; moreover, by rate control strategy, the detrimental hemodynamic effects of AF persist, leading to a further impair in LV function, cardiac output, and symptoms. This frequently leads to the fact that, despite optimal medical therapy (OMT) for at least 3 months, the patients require implantable cardioverter defibrillator (ICD), and, in case of poor rate control AV node ablation with resynchronization therapy (CRT). The latter, however, infer pacemaker (PM)-dependence, and relate to a not negligible risk of cardiac rhythm device peri-implantation and long-term complications (infections, leads failure).
On the other side rhythm control may represent an option. In the general population, in fact, recent evidences suggest an advantage over rate control concerning survival, quality of life and thromboembolic events. The main limitation, however, stands in how to achieve rhythm control: antiarrhythmic therapy has several side effects (amiodarone, in fact the only recommended drug, is thrived by frequent adverse events) and transcatheter AF ablation has been assessed only in modest sample size studies.
Available literature focusing on a comparison between different management strategies in patients with CHF and AF is limited. A small randomized study compared pulmonary veins (PVs) isolation to AV node ablation and biventricular PM implantation, showing improved 6-month outcome, defined by a composite end point of LV ejection fraction, 6-minutes walking distance and Minnesota Living with Heart Failure (MLWHF) questionnaire, in patients treated by PVs isolation. However, only 81 patients were enrolled in this short-term study, and no hard end point tested. More recently, and actually ongoing, the AATAC-AF study, is comparing amiodarone and catheter ablation in patients with chronic AF and an implantable device (biventricular PM or ICD). Also in this case, the preliminary results support an improved 24 month outcome, in terms of sinus rhythm (SR) achievement, quality of life and LV function, in patients undergoing AF ablation .
In addition to these direct comparisons, other indirect evidences support catheter ablation rhythm control . In a recent meta-analysis, PVs isolation, linear lesions and ablation of fragmented potentials in left atrium, although with a relatively high need for repeated procedures, have proven not only to be safe but also effective in improving symptoms (related to both CHF and AF), LV function and maintaining SR. In fact, in this analysis, 60% of the patients with a left ventricular function below 35% at baseline improved to a value above this limit following AF ablation.
We therefore designed this multicenter, randomized controlled trial aiming to assess if, in recently diagnosed (less than 6 months) and optimally treated CHF patients with impaired LV function, AF catheter ablation is effective in improving LV function and clinical functional class, potentially driving to a reduction of device implantations (ICD/CRTs).
The aim of the present study is to assess within patients with concomitant CHF and persistent AF whether AF ablation, compared to optimal rate control strategy, is superior in terms of LV function and clinical functional class. In addition, long-term outcome and complications will be recorded and compared.
This study is a prospective, multicenter, randomized, two-arms parallel-group trial. Randomization is performed through a 24-hour, centralized, computer system. Enrollment will occur at 5 centers in Italy. The study protocol will receive approval by the ethics review board at each institution before study enrollment, and patients will be randomized to undergo either arm of the study in an open fashion, due to the nature of the alternative procedures.
Written informed consent, including description of the procedure and risk of complications, is obtained from each patient before study inclusion.
At 3, 6 and 12 months from the index procedure a complete follow-up visit is performed for all patients in both study arms. Clinical assessment will include signs and symptoms of heart failure, NYHA functional class evaluation, quality of life assessment by MLWHF questionnaire and a 12-lead ECG. Additionally, all patients will undergo a complete transthoracic echocardiographic evaluation, including LV ejection fraction, end-diastolic and end-systolic volumes, LV diastolic function, LA volume, mitral regurgitation or stenosis grade, right ventricular diameter and systolic function (TAPSE). A 6-minute walking test will be performed aiming to reproducibly quantify the functional class of the patients at each scheduled evaluation. A 24-hour ECG Holter will be performed in all patients, to detect AF recurrences in the AF ablation arm, mean heart rate (both for patients in AF and SR) and ventricular arrhythmias burden. For patients implanted with a device, AF burden, ICD interventions and percentage of biventricular pacing will be recorded. Finally, the incidence of heart failure hospitalizations, ischemic or hemorrhagic strokes and all-cause mortality will be assessed in both groups. Additional clinical assessment will be performed in case of heart failure acute worsening.
No external source of funding will contribute to this study, and no conflict of interest has been to be declared. All data are independently collected, managed, and analyzed with a restricted-access database. The steering committee, is responsible for the design and conduct of the study and for the drafting and editing of the results. The steering committee will have full access to the final study data and statistical analysis.
- Conditions
- Persistent Atrial Fibrillation, Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction
- Being tested
- Atrial fibrillation catheter ablation, Rate control
- Keywords
- atrial fibrillation, congestive heart failure, catheter ablation, rate control, left ventricular function
- Medical subject headings
- Atrial Fibrillation, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atrial fibrillation catheter ablationProcedure or surgery
Rate controlProcedure or surgery
Composite of optimal medical therapy and device implantation
| Study group | Role | What they receive |
|---|---|---|
| Atrial fibrillation catheter ablation | Experimental | Atrial fibrillation (AF) catheter ablation is performed following each Center's common practice. Activated clotting time (ACT) is maintained above 350 seconds. The left atrium (LA) is accessed by transseptal puncture or through a patent foramen ovale. A multipolar catheter and an irrigated-tip ablation catheter are inserted into the LA and a 3-dimensional reconstruction of the LA and pulmonary veins (PVs) ostia is performed. The mainstay is to obtain a complete antral PVs isolation, defined by complete elimination of PVs potentials. PVs isolation may be accompanied by the creation of linear lesions (roof line, left isthmus) or ablation of complex fractioned atrial electrograms. Patients are discharged on oral anticoagulation and optimal medical therapy. Each center will evaluate patients for ICD implantation; a loop recorder may be implanted if within routine clinical practice. Receives: Procedure: Atrial fibrillation catheter ablation |
| Rate control arm | Experimental | Patients randomized to rate control only arm will undergo ICD implantation and optimization of the rate control therapy. In case of uncontrolled ventricular rate at 24-h ECG Holter, defined as a mean resting heart rate higher than 90 bpm, patients will receive atrioventricular (AV) node ablation and resyncronization therapy (CRT-D) implantation, performed following common practice at each Center. In case of failure or technical difficulties of the transvenous approach, epicardial screw-in or steroid-eluting passive lead is implanted via a limited thoracotomy. Transcatheter AV node ablation is performed as follows: a non-irrigated tip ablation catheter is introduced on the right side of the interatrial septum and ablation performed on the fast pathway region or the smallest His bundle signal. The goal of the procedure is AV modulation below 30 bpm or complete AV block. Receives: Procedure: Rate control |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite of the improvement of left ventricular ejection fraction above 35% and concomitant NYHA class lower than II, measured as number of patients reporting both conditions at follow-up
Measured: 6 months
Secondary outcomes (7)
6-minute walking test distance, meaused in metres
Measured: 3, 6 and 12 months
quality of life, assessed with Minnesota Living With Heart Failure questionnaire score
Measured: 3, 6 and 12 months
number of heart failure hospitalizations
Measured: 3, 6 and 12 months
number of ICD interventions
Measured: 3, 6 and 12 months
number of patients suffering ischemic or hemorrhagic stroke
Measured: 3, 6 and 12 months
all-cause mortality
defined as number of patients died during follow-up
Measured: 3, 6 and 12 months
periprocedural major complications
composite of death, cerebrovascular accidents, cardiac tamponade, pneumothorax, phrenic nerve persistent injury, access site pseudoaneurysm/fistula/hematoma requiring drainage
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2015 (estimated)
- Study startJan 2016
- Primary completionJun 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Persistent Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Collaborators
- Centro Cardiologico Monzino, Humanitas Research Hospital IRCCS, Rozzano-Milan, University of Padova, Policlinico Casilino ASL RMB
- Responsible party
- Principal investigator, Fiorenzo Gaita, University of Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02509754
- Sponsor's protocol ID
- FG062015TRN
- Acronym
- AFARC-LVF
- Status last verified
- Dec 2015
- First submitted
- 22 Jul 2015
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994 Mar 16;271(11):840-4.
PubMed 8114238Savelieva I, John Camm A. Atrial fibrillation and heart failure: natural history and pharmacological treatment. Europace. 2004 Sep;5 Suppl 1:S5-19. doi: 10.1016/j.eupc.2004.07.003.
PubMed 15450275Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1825-33. doi: 10.1056/NEJMoa021328.
PubMed 12466506Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003 Jun 17;107(23):2920-5. doi: 10.1161/01.CIR.0000072767.89944.6E. Epub 2003 May 27.
PubMed 12771006Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH, Pires LA; PAVE Study Group. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. 2005 Nov;16(11):1160-5. doi: 10.1111/j.1540-8167.2005.50062.x.
PubMed 16302897McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-847. doi: 10.1093/eurheartj/ehs104. Epub 2012 May 19. No abstract available.
PubMed 22611136Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 Aug;34(29):2281-329. doi: 10.1093/eurheartj/eht150. Epub 2013 Jun 24. No abstract available.
PubMed 23801822Gasparini M, Auricchio A, Regoli F, Fantoni C, Kawabata M, Galimberti P, Pini D, Ceriotti C, Gronda E, Klersy C, Fratini S, Klein HH. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol. 2006 Aug 15;48(4):734-43. doi: 10.1016/j.jacc.2006.03.056. Epub 2006 Jul 24.
PubMed 16904542Gasparini M, Auricchio A, Metra M, Regoli F, Fantoni C, Lamp B, Curnis A, Vogt J, Klersy C; Multicentre Longitudinal Observational Study (MILOS) Group. Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation. Eur Heart J. 2008 Jul;29(13):1644-52. doi: 10.1093/eurheartj/ehn133. Epub 2008 Apr 4.
PubMed 18390869Ezzat VA, Lee V, Ahsan S, Chow AW, Segal O, Rowland E, Lowe MD, Lambiase PD. A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation? Open Heart. 2015 Feb 17;2(1):e000198. doi: 10.1136/openhrt-2014-000198. eCollection 2015.
PubMed 25745566Nof E, Epstein LM. Complications of cardiac implants: handling device infections. Eur Heart J. 2013 Jan;34(3):229-36. doi: 10.1093/eurheartj/ehs352. Epub 2012 Oct 22.
PubMed 23091204Kleemann T, Becker T, Doenges K, Vater M, Senges J, Schneider S, Saggau W, Weisse U, Seidl K. Annual rate of transvenous defibrillation lead defects in implantable cardioverter-defibrillators over a period of >10 years. Circulation. 2007 May 15;115(19):2474-80. doi: 10.1161/CIRCULATIONAHA.106.663807. Epub 2007 Apr 30.
PubMed 17470696Ionescu-Ittu R, Abrahamowicz M, Jackevicius CA, Essebag V, Eisenberg MJ, Wynant W, Richard H, Pilote L. Comparative effectiveness of rhythm control vs rate control drug treatment effect on mortality in patients with atrial fibrillation. Arch Intern Med. 2012 Jul 9;172(13):997-1004. doi: 10.1001/archinternmed.2012.2266.
PubMed 22664954Tsadok MA, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Humphries KH, Tu JV, Behlouli H, Pilote L. Rhythm versus rate control therapy and subsequent stroke or transient ischemic attack in patients with atrial fibrillation. Circulation. 2012 Dec 4;126(23):2680-7. doi: 10.1161/CIRCULATIONAHA.112.092494. Epub 2012 Nov 2.
PubMed 23124034Gaita F, Corsinovi L, Anselmino M, Raimondo C, Pianelli M, Toso E, Bergamasco L, Boffano C, Valentini MC, Cesarani F, Scaglione M. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol. 2013 Nov 19;62(21):1990-1997. doi: 10.1016/j.jacc.2013.05.074. Epub 2013 Jul 10.
PubMed 23850917
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atrial Fibrillation Ablation Compared to Rate Control Strategy in Patients With Recently Diagnosed Impaired Left Ventricular Function: a Multicenter, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02509754
- Acronym / sponsor ID
- AFARC-LVF / FG062015TRN
- Conditions
- Persistent Atrial Fibrillation, Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction
- Keywords
- atrial fibrillation, congestive heart failure, catheter ablation, rate control, left ventricular function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Collaborators
- Centro Cardiologico Monzino, Humanitas Research Hospital IRCCS, Rozzano-Milan, University of Padova, Policlinico Casilino ASL RMB
- Study start
- Jan 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 28 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Atrial fibrillation (AF) and congestive heart failure (CHF) are two epidemics that share several physiopathological links. CHF patients present a significantly increased risk of developing AF and the related detrimental hemodynamic effects are even more relevant than in patients without CHF.
Within CHF patients rate control is the most widely used strategy to manage AF, having proved non-inferior to rhythm control strategies. However, by this strategy, the hemodynamic effects of AF persist, not contrasting the natural evolution towards progressive left ventricular (LV) function, cardiac output , and symptoms worsening. Rhythm control strategy, instead, has shown, in the general population, advantages over rate control concerning survival, quality of life and thromboembolic events. The main limitation is that antiarrhythmic therapy used to achieve this goal has several side effects, and that transcatheter AF ablation has been assessed only in modest sample size studies.
Available literature focusing on a direct comparison between two specific management strategies in patients with CHF and AF is limited to a small randomized study comparing pulmonary veins isolation to AV node ablation and biventricular PM implantation (PABA-CHF study). Additional indirect evidences may derive from meta-analyses of observational studies.
The investigators therefore designed this multicenter, randomized controlled trial aiming to assess if, in recently diagnosed (less than 6 months) and optimally treated CHF patients with impaired LV function, AF catheter ablation is effective in improving LV function and clinical functional class, potentially driving to a reduction of device implantations (ICD/CRTs).
Detailed description
Atrial fibrillation (AF) is the most common arrhythmia among the general population. Its prevalence increases with advanced age but also with the presence of structural heart disease. In particular patients suffering from congestive heart failure (CHF) with low left ventricular (LV) ejection fraction present a significantly increased risk of developing AF and its detrimental hemodynamic effects, due to the loss of atrial contraction, and fast and irregular beats, are an even more relevant compared to patients without CHF.
In CHF patients rate control is the most widely used strategy to manage AF; in fact, it has proved non-inferior to rhythm control strategies concerning survival rates . However, adequate ventricular rate is difficult to achieve; moreover, by rate control strategy, the detrimental hemodynamic effects of AF persist, leading to a further impair in LV function, cardiac output, and symptoms. This frequently leads to the fact that, despite optimal medical therapy (OMT) for at least 3 months, the patients require implantable cardioverter defibrillator (ICD), and, in case of poor rate control AV node ablation with resynchronization therapy (CRT). The latter, however, infer pacemaker (PM)-dependence, and relate to a not negligible risk of cardiac rhythm device peri-implantation and long-term complications (infections, leads failure).
On the other side rhythm control may represent an option. In the general population, in fact, recent evidences suggest an advantage over rate control concerning survival, quality of life and thromboembolic events. The main limitation, however, stands in how to achieve rhythm control: antiarrhythmic therapy has several side effects (amiodarone, in fact the only recommended drug, is thrived by frequent adverse events) and transcatheter AF ablation has been assessed only in modest sample size studies.
Available literature focusing on a comparison between different management strategies in patients with CHF and AF is limited. A small randomized study compared pulmonary veins (PVs) isolation to AV node ablation and biventricular PM implantation, showing improved 6-month outcome, defined by a composite end point of LV ejection fraction, 6-minutes walking distance and Minnesota Living with Heart Failure (MLWHF) questionnaire, in patients treated by PVs isolation. However, only 81 patients were enrolled in this short-term study, and no hard end point tested. More recently, and actually ongoing, the AATAC-AF study, is comparing amiodarone and catheter ablation in patients with chronic AF and an implantable device (biventricular PM or ICD). Also in this case, the preliminary results support an improved 24 month outcome, in terms of sinus rhythm (SR) achievement, quality of life and LV function, in patients undergoing AF ablation .
In addition to these direct comparisons, other indirect evidences support catheter ablation rhythm control . In a recent meta-analysis, PVs isolation, linear lesions and ablation of fragmented potentials in left atrium, although with a relatively high need for repeated procedures, have proven not only to be safe but also effective in improving symptoms (related to both CHF and AF), LV function and maintaining SR. In fact, in this analysis, 60% of the patients with a left ventricular function below 35% at baseline improved to a value above this limit following AF ablation.
We therefore designed this multicenter, randomized controlled trial aiming to assess if, in recently diagnosed (less than 6 months) and optimally treated CHF patients with impaired LV function, AF catheter ablation is effective in improving LV function and clinical functional class, potentially driving to a reduction of device implantations (ICD/CRTs).
The aim of the present study is to assess within patients with concomitant CHF and persistent AF whether AF ablation, compared to optimal rate control strategy, is superior in terms of LV function and clinical functional class. In addition, long-term outcome and complications will be recorded and compared.
This study is a prospective, multicenter, randomized, two-arms parallel-group trial. Randomization is performed through a 24-hour, centralized, computer system. Enrollment will occur at 5 centers in Italy. The study protocol will receive approval by the ethics review board at each institution before study enrollment, and patients will be randomized to undergo either arm of the study in an open fashion, due to the nature of the alternative procedures.
Written informed consent, including description of the procedure and risk of complications, is obtained from each patient before study inclusion.
At 3, 6 and 12 months from the index procedure a complete follow-up visit is performed for all patients in both study arms. Clinical assessment will include signs and symptoms of heart failure, NYHA functional class evaluation, quality of life assessment by MLWHF questionnaire and a 12-lead ECG. Additionally, all patients will undergo a complete transthoracic echocardiographic evaluation, including LV ejection fraction, end-diastolic and end-systolic volumes, LV diastolic function, LA volume, mitral regurgitation or stenosis grade, right ventricular diameter and systolic function (TAPSE). A 6-minute walking test will be performed aiming to reproducibly quantify the functional class of the patients at each scheduled evaluation. A 24-hour ECG Holter will be performed in all patients, to detect AF recurrences in the AF ablation arm, mean heart rate (both for patients in AF and SR) and ventricular arrhythmias burden. For patients implanted with a device, AF burden, ICD interventions and percentage of biventricular pacing will be recorded. Finally, the incidence of heart failure hospitalizations, ischemic or hemorrhagic strokes and all-cause mortality will be assessed in both groups. Additional clinical assessment will be performed in case of heart failure acute worsening.
No external source of funding will contribute to this study, and no conflict of interest has been to be declared. All data are independently collected, managed, and analyzed with a restricted-access database. The steering committee, is responsible for the design and conduct of the study and for the drafting and editing of the results. The steering committee will have full access to the final study data and statistical analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atrial fibrillation catheter ablation | Experimental | Procedure: Atrial fibrillation catheter ablationAtrial fibrillation (AF) catheter ablation is performed following each Center's common practice. Activated clotting time (ACT) is maintained above 350 seconds. The left atrium (LA) is accessed by transseptal puncture or through a patent foramen ovale. A multipolar catheter and an irrigated-tip ablation catheter are inserted into the LA and a 3-dimensional reconstruction of the LA and pulmonary veins (PVs) ostia is performed. The mainstay is to obtain a complete antral PVs isolation, defined by complete elimination of PVs potentials. PVs isolation may be accompanied by the creation of linear lesions (roof line, left isthmus) or ablation of complex fractioned atrial electrograms. Patients are discharged on oral anticoagulation and optimal medical therapy. Each center will evaluate patients for ICD implantation; a loop recorder may be implanted if within routine clinical practice. |
| Rate control arm | Experimental | Procedure: Rate controlPatients randomized to rate control only arm will undergo ICD implantation and optimization of the rate control therapy. In case of uncontrolled ventricular rate at 24-h ECG Holter, defined as a mean resting heart rate higher than 90 bpm, patients will receive atrioventricular (AV) node ablation and resyncronization therapy (CRT-D) implantation, performed following common practice at each Center. In case of failure or technical difficulties of the transvenous approach, epicardial screw-in or steroid-eluting passive lead is implanted via a limited thoracotomy. Transcatheter AV node ablation is performed as follows: a non-irrigated tip ablation catheter is introduced on the right side of the interatrial septum and ablation performed on the fast pathway region or the smallest His bundle signal. The goal of the procedure is AV modulation below 30 bpm or complete AV block. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Recent (no longer than 6 months) diagnosis of congestive heart failure, defined as left ventricular ejection fraction lower or equal than 35% along with the presence of symptoms of heart failure, with a NYHA class II, III or ambulatory IV;
- Optimal medical therapy from at least 3 months (including a beta-blocker, an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) and, in NYHA III and IV patients, spironolactone);
- Persistent atrial fibrillation (at least 3 months or, alternatively, a minimum of two previous episodes lasting longer than 7 days);
- Refractory to at least one, or intolerant to, antiarrhythmic drug/s;
- Must be able to provide written informed consent.
Key exclusion criteria (12 listed)
- Reversible causes of atrial fibrillation or congestive heart failure;
- Permanent or long-standing persistent atrial fibrillation (lasting more than 1 year);
- Previous surgical or transcatheter AF ablation;
- Previously implanted CRT with or without concomitant AV node ablation;
- QRS duration above 150 msec or above 120 msec in the presence of complete left bundle branch block (class IIa indication for CRT implantation);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atrial fibrillation catheter ablation | Procedure or surgery | Atrial fibrillation catheter ablation |
| Rate controlComposite of optimal medical therapy and device implantation | Procedure or surgery | Rate control arm |
Primary outcome
composite of the improvement of left ventricular ejection fraction above 35% and concomitant NYHA class lower than II, measured as number of patients reporting both conditions at follow-up
Time frame: 6 months
7 secondary outcomes
6-minute walking test distance, meaused in metres
Time frame: 3, 6 and 12 months
quality of life, assessed with Minnesota Living With Heart Failure questionnaire score
Time frame: 3, 6 and 12 months
number of heart failure hospitalizations
Time frame: 3, 6 and 12 months
number of ICD interventions
Time frame: 3, 6 and 12 months
number of patients suffering ischemic or hemorrhagic stroke
Time frame: 3, 6 and 12 months
all-cause mortality
Time frame: 3, 6 and 12 months
periprocedural major complications
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
- Background: PubMed 8114238Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994 Mar 16;271(11):840-4.
- Background: PubMed 15450275Savelieva I, John Camm A. Atrial fibrillation and heart failure: natural history and pharmacological treatment. Europace. 2004 Sep;5 Suppl 1:S5-19. doi: 10.1016/j.eupc.2004.07.003.
- Background: PubMed 12466506Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1825-33. doi: 10.1056/NEJMoa021328.
- Background: PubMed 12771006Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003 Jun 17;107(23):2920-5. doi: 10.1161/01.CIR.0000072767.89944.6E. Epub 2003 May 27.
- Background: PubMed 16302897Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH, Pires LA; PAVE Study Group. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. 2005 Nov;16(11):1160-5. doi: 10.1111/j.1540-8167.2005.50062.x.
- Background: PubMed 22611136McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012 Jul;33(14):1787-847. doi: 10.1093/eurheartj/ehs104. Epub 2012 May 19. No abstract available.
- Background: PubMed 23801822Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 Aug;34(29):2281-329. doi: 10.1093/eurheartj/eht150. Epub 2013 Jun 24. No abstract available.
- Background: PubMed 16904542Gasparini M, Auricchio A, Regoli F, Fantoni C, Kawabata M, Galimberti P, Pini D, Ceriotti C, Gronda E, Klersy C, Fratini S, Klein HH. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol. 2006 Aug 15;48(4):734-43. doi: 10.1016/j.jacc.2006.03.056. Epub 2006 Jul 24.
- Background: PubMed 18390869Gasparini M, Auricchio A, Metra M, Regoli F, Fantoni C, Lamp B, Curnis A, Vogt J, Klersy C; Multicentre Longitudinal Observational Study (MILOS) Group. Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation. Eur Heart J. 2008 Jul;29(13):1644-52. doi: 10.1093/eurheartj/ehn133. Epub 2008 Apr 4.
- Background: PubMed 25745566Ezzat VA, Lee V, Ahsan S, Chow AW, Segal O, Rowland E, Lowe MD, Lambiase PD. A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation? Open Heart. 2015 Feb 17;2(1):e000198. doi: 10.1136/openhrt-2014-000198. eCollection 2015.
- Background: PubMed 23091204Nof E, Epstein LM. Complications of cardiac implants: handling device infections. Eur Heart J. 2013 Jan;34(3):229-36. doi: 10.1093/eurheartj/ehs352. Epub 2012 Oct 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Matta, M.D. contact
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atrial fibrillation catheter ablation in people with Persistent Atrial Fibrillation and Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction, run by University of Turin, Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fiorenzo Gaita, M.D., Prof. (+390116335570, fiorenzo.gaita@unito.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
composite of the improvement of left ventricular ejection fraction above 35% and concomitant NYHA class lower than II, measured as number of patients reporting both conditions at follow-up (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02509754, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2015.