Clinical Investigation
Electrophysiology
Clinical predictors of atrial fibrillation recurrence in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico–Atrial Fibrillation (GISSI-AF) trial

https://doi.org/10.1016/j.ahj.2010.02.016Get rights and content

Background

Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm (SR). Identifying risk factors for recurrence may help define the best strategy for secondary prevention.

Methods

The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks. Patients were randomized to valsartan or placebo; all other treatments for AF or underlying heart diseases were allowed. Primary end points were time to first recurrence of AF and proportion of patients with >1 AF episode during 1-year follow-up. We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model.

Results

Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months, independent of the modality of SR restoration, spontaneous (HR 1.42, 95% CI 1.14-1.77, P = .002), or by cardioversion (HR 1.19, 95% CI 1.01-1.40, P = .038), and a lower heart rate during SR (HR 0.99, 95% CI 0.99-1.00, P = .052). The risk factors were the same for >1 AF recurrence. Patients treated with amiodarone had a lower risk for both end points (P < .0001 and P = .017), whereas those on diuretics had a greater risk (P = .009 and P = .003).

Conclusions

In the GISSI-AF study population, AF history had significant prognostic value independent of the modality of SR restoration. Amiodarone and diuretic treatment affected the rate of AF recurrence.

Section snippets

Methods

The rationale, design, and results of GISSI-AF trial have already been published24, 25 (Clinical Trials.gov identifier: NCT00376272). It was a prospective, multicenter, randomized, double blind, placebo-controlled trial to assess whether addition of the angiotensin II-receptor blocker (ARB) valsartan to established therapies could reduce recurrence of AF in patients with a history of AF associated with cardiovascular diseases. The ethics committee at all participating centers approved the

Results

The baseline characteristics of study population at the time of enrolment according to first recurrence of AF within 1 year of follow-up are presented in Table I.

Discussion

GISSI-AF was a pragmatic trial with broad selection criteria to mimic real clinical practice as much as possible. This post hoc analysis suggests that, in GISSI-AF patients, a history of arrhythmia and low sinus rate at enrolment were predictors of AF recurrences within a 1-year follow-up. No other clinical, demographic, or electrocardiographic parameters were associated with AF recurrences, thus precluding the possibility of devising an arrhythmic risk score for use in the clinical setting. We

Conclusions

The GISSI-AF data indicate that it is impossible to devise an arrhythmic risk score in this patient population on the basis of clinical, demographic, and electrocardiographic parameters. Only AF history and, in particular, the presence of at least 2 episodes of AF in the last 6 months had significant prognostic value independent of the modality of SR restoration.

We confirmed the antiarrhythmic effects of amiodarone in hypertensive patients. We also report for the first time the negative

References (38)

  • KannelW.B. et al.

    Epidemiologic features of atrial fibrillation: the Framingham study

    N Engl J Med

    (1982)
  • GoA.S. et al.

    Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention; the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study

    JAMA

    (2001)
  • PozzoliM. et al.

    Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: a prospective study in 344 patients with baseline sinus rhythm

    J Am Coll Cardiol

    (1998)
  • DriesD.L. et al.

    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)
  • MathewJ. et al.

    Incidence, predictive factors, and prognostic significance of supraventricular tachyarrhythmias in congestive heart failure

    Chest

    (2000)
  • RoyD. et al.

    Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators

    N Engl J Med

    (2000)
  • Lafuente-LafuenteC. et al.

    Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation

    Arch Intern Med

    (2006)
  • KoberL. et al.

    Increased mortality after dronedarone therapy for severe heart failure

    N Engl J Med

    (2008)
  • CappatoR. et al.

    Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation

    Circulation

    (2005)
  • FusterV. et al.

    ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation)

    Eur Heart J

    (2006)
  • HohnloserS. et al.

    Rhythm or rate control in atrial fibrillation. Pharmacological Intervention in Atrial Fibrillation (PIAF)

    Lancet

    (2000)
  • WyseD.G. et al.

    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)
  • Van GelderI.C. et al.

    Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study Group (RACE). A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation

    N Engl J Med

    (2002)
  • RoyD. et al.

    Rhythm control versus rate control for atrial fibrillation and heart failure

    N Engl J Med

    (2008)
  • DuytsschaeverM. et al.

    Factors influencing long term persistence of sinus rhythm after first electrical cardioversion for atrial fibrillation

    PACE

    (1998)
  • LehtoM. et al.

    Persistent atrial fibrillation: a population based study of patients with their first cardioversion

    Int J Cardiol

    (2003)
  • DahlinJ. et al.

    Poor maintenance of sinus rhythm after electrical cardioversion of patients with atrial fibrillation or flutter: a 5-year follow-up of 268 consecutive patients

    Scand Cardiovasc J

    (2003)
  • RaittM.H. et al.

    Prediction of the recurrence of atrial fibrillation after cardioversion in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study

    Am Heart J

    (2006)
  • BorianiG. et al.

    Electrical cardioversion for persistent atrial fibrillation or atrial flutter in clinical practice: predictors of long-tem outcome

    Int J Clin Pract

    (2007)

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      For example, in the Gruppo Italiano per lo Studio della Sopravvivenza Nell'Infarto Miocardico—Atrial Fibrillation trial,30 which included 1,442 patients with ≥2 documented AF episodes in the previous 6 months, there was no observed significant difference at baseline in prevalence of DM between the group in which AF recurred and the group in which AF did not recur (13.9% vs 15.4%, p = 0.44).

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    RCT# NCT00376272.

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    A complete list of GISSI-AF study committees, collaborators, and participating centers is published in the New England Journal of Medicine 2009;360:1606-1617.

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