Advertisement

Outcomes and complications of catheter ablation for atrial fibrillation in females

Published:October 26, 2009DOI:https://doi.org/10.1016/j.hrthm.2009.10.025

      Background

      Most atrial fibrillation (AF) ablation studies have consisted predominantly of males; accordingly, there is a paucity of information on the safety and efficacy of catheter ablation in a large cohort of female AF patients.

      Objective

      The purpose of this study was to evaluate catheter ablation for AF in female patients.

      Methods

      From January 2005 to May 2008, 3265 females underwent pulmonary vein antrum isolation. Success rates, patient profiles, and complications were collected.

      Results

      Approximately 16% of our population was female (P <.001). Females were older (59 ± 13 vs. 56 ± 19 years; P <.01) and had a lower prevalence of paroxysmal atrial fibrillation (PAF; 46% vs. 55%; P <.001). Females failed more antiarrhythmics (4 ± 1 vs. 2 ± 3; P = .04) and were referred later for catheter ablation (6.51 ± 7 vs. 4.85 ± 6.5 years; P = .02) than males. More females failed ablation (31.5% vs. 22.5%; P = .001) and had nonantral sites of firing than males (P <.001). Female patients had 11 (2.1%) hematomas versus 27 (0.9%) in males.

      Conclusions

      Five times as many males underwent catheter ablation than females. Females failed more ablations possibly because of a higher prevalence of nonantral firing, non-PAF, and longer history of AF. Females had more bleeding complications than males.

      Keywords

      Abbreviations:

      AF (atrial fibrillation), BMI (body mass index), EF (ejection fraction), LA (left atrium), LSPAF (long-standing persistent atrial fibrillation), PAF (paroxysmal atrial fibrillation), PV (pulmonary vein), PVAI (pulmonary vein antrum isolation)
      Over the past decade, catheter ablation for the management of atrial fibrillation (AF) has evolved from a provisional therapy to one that many electrophysiologists routinely use.
      • Benjamin E.J.
      • Wolf P.A.
      • D'Agostina R.B.
      • et al.
      Impact of atrial fibrillation on the risk of death: the Framingham Heart Study.
      The majority of AF ablation studies had predominantly consisted of males; accordingly, there is a paucity of information on the safety and efficacy of catheter ablation in a large cohort of female AF patients.
      While male gender is an independent risk factor for AF, so is increasing age. Since women tend to have longer life spans than men, the absolute number of men and women with AF is similar.
      • Rienstra M.
      • Van Veldhuisen D.J.
      • Hagens V.E.
      • et al.
      Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) Study.
      Moreover, in women, AF is often more symptomatic and is associated with greater cardiovascular mortality, a higher risk of thromboembolic stroke, and a poorer quality of life than in men.
      • Humphries K.H.
      • Kerr C.R.
      • Connolly S.J.
      • et al.
      New-onset atrial fibrillation: sex differences in presentation, treatment and outcome.
      Considering these issues, it becomes relevant to assess the safety and efficacy of pulmonary vein antrum isolation (PVAI) in women.
      The objective of this study was to (1) evaluate catheter ablation procedural success and complication rates between males and females patients and (2) to further investigate whether certain clinical characteristics predicted procedural failure in an all-female cohort.

      Methods

      Patient population

      We screened 3265 consecutive patients with highly symptomatic and drug-refractory AF who underwent ablation at Sutter Pacific Medical Center, San Francisco, California; Metro Health Case Western Reserve, Cleveland, Ohio; Stanford University, Palo Alto, California; Akron General Hospital, Akron, Ohio; and Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, Texas from January 2005 to May 2008. All female patients were selected from each center's AF ablation registry. Male patients served as a control population. This multicenter study was retrospective; however, the databases at each center were prospectively collected. This study has Institutional Review Board approval.

      Definitions

      AF was classified according to the 2007 expert consensus statement of the Heart Rhythm Society/Heart Rhythm Association/European Cardiac Arrhythmia Society on catheter and surgical ablation of AF.
      • Calkins H.
      • Brugada J.
      • Packer D.L.
      • et al.
      HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. European Heart Rhythm Association (EHRA); European Cardiac Arrhythmia Society (ECAS); American College of Cardiology (ACC); American Heart Association (AHA); Society of Thoracic Surgeons (STS).
      AF was classified as paroxysmal AF (PAF), persistent AF, and long-standing persistent AF (LSPAF). The nonparoxysmal AF group was made up of all persistent AF and LSPAF cases. Survival status was found by using the National Death Registry and the Social Security Death Index.
      Procedural failure is defined as any episode of AF/atrial tachycardia without antiarrhythmic drugs that lasted longer than 1 minute after the first 8 weeks. Episodes occurring during the first 8 weeks (blanking period) after the procedure were not considered to be recurrences. Success rates were reported in terms of primary ablation at the participating centers. Extra–pulmonary vein (PV) firing sites were defined as any sites of firing outside of the PV antrum before or after the administration of high-dose isoproterenol. Non-PV triggers were documented by the presence of firing leading to short bursts of tachycardia or AF after the completion of the basic procedure. Firing was mostly disclosed by administration of high-dose isoproterenol. Complications included stroke, PV stenosis/occlusion, atrioesophageal fistula, pericardial effusion, hematoma, and pseudoaneurysm.

      Ablation protocol

      Before ablation

      Antiarrhythmic drugs were discontinued four to five half-lives before ablation. Patients on amiodarone discontinued the medication 5–6 months before ablation. Patients with persistent AF or LSPAF had a transesophageal echocardiography or were treated with warfarin for approximately 5–6 weeks before the procedure. Warfarin was stopped 2–3 days before the procedure and bridged with 0.5 mg/kg of low molecular weight heparin. In one center, patients who had procedures after June 2005 did not discontinue warfarin before the procedure, and the international normalized ratio was maintained between 2.0 and 3.0.

      Ablation procedure

      All patients underwent the ablation procedure using the same ablation strategy. We used a circular mapping catheter (Lasso, Biosense Webster, Diamond Bar, CA) and a 3.5-mm open-irrigation-tip catheter (ThermoCool, Biosense Webster) for ablation. Intracardiac echocardiography was used to image the anatomy of the PVs. In additional, an electroanatomical mapping system was used to confirm the distribution of scar.
      During ablation with the open-irrigation catheter, radiofrequency energy was delivered at 40 W for a maximum of 20 seconds at each site. At sites where the ablation tip was parallel to the wall of the left atrium (LA), the energy was increased to 45 W. Power was limited to 35 W on the posterior wall and for a maximum of 20 seconds per application. Energy delivery was discontinued when the esophageal temperature probe reached 39°C. If the temperature in the esophagus increased rapidly, the power was lowered to 30 W. The esophageal course was monitored with intracardiac echocardiography and with fluoroscopy through the esophageal probe. The height of the esophageal temperature probe was adjusted in relation to the position of the ablation catheter for a more accurate temperature monitoring.
      In patients with paroxysmal AF, the antrum of the PVs including the entire posterior wall between the PVs was isolated. In addition, the tissue anterior to the right PVs along the left septum was ablated. The endpoint was defined as elimination of all the PV potentials along the antra or inside the veins (entry block). Occasionally, exit block was also shown for some veins after isolation (dissociated firing). The superior vena cava along the ostium was also ablated if PV-like potentials were found around this region and when high-output pacing did not capture the phrenic nerve.
      • Arruda M.
      • Mlcochova H.
      • Prasad S.K.
      • et al.
      Electrical isolation of the superior vena cava: an adjunctive strategy to pulmonary vein antrum isolation improving the outcome of AF ablation.
      After ablation, all patients were administered high-dose isoproterenol challenge (20–30 μg/min) to ensure electrical disconnection or to locate extra non-PV firing sites that were not previously present. All sites that showing firing were ablated.
      • Kanj M.H.
      • Wazni O.
      • Fahmy T.
      • et al.
      Pulmonary vein antral isolation using an open irrigation ablation catheter for the treatment of atrial fibrillation: a randomized pilot study.
      • Bhargava M.
      • Di Biase L.
      • Mohanty P.
      • et al.
      Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: results from a multicenter study.
      In patients with nonparoxysmal AF, the PV antrum and the superior vena cava were isolated. Ablation in the posterior wall was extended down to the coronary sinus, and the left side of the septum was ablated as well. In addition, the left and the right atrium (including the coronary sinus) were mapped to identify areas with fractionation. These areas were targeted until complete elimination of fractionated atrial electrograms. Fractionated electrograms were defined as atrial electrograms with fractionation and were composed of two deflections or more and/or had continuous activity of the baseline or atrial electrograms with a continuous cycle length ≤120 ms as described by Nademanee et al.
      • Nademanee K.
      • McKenzie J.
      • Kosar E.
      • et al.
      A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate.
      After ablation, high-dose isoproterenol challenge (20–30 μg/min) was performed in all patients to ensure electrical disconnection or to locate extra non-PV firing sites that were not previously present. Non-PV firing sites were ablated with conventional activation mapping.

      Anticoagulation

      A heparin bolus (100–150 U/kg) was given before transseptal punctures. The infusion rate was adjusted to keep the activated clotting time between 350 and 450 seconds. After PVAI, heparin was discontinued and IV protamine 20–30 mg was given. Sheaths were pulled when the activated clotting time was <280 seconds. At the end of all procedures, patients were given oral 325 mg of aspirin before leaving the electrophysiology laboratory. Oral anticoagulation with warfarin was resumed on the same night of the procedure. A half dose of subcutaneous low molecular weight heparin was administered twice a day until the patient's international normalized ratio was therapeutic. Since 2005, one center has kept its patients on warfarin during the procedure. The other intuitions have kept their patients on warfarin during the procedure starting from June to September 2007.

      Follow-up

      All patients were discharged on oral anticoagulation therapy (warfarin). Follow-up was scheduled at 3, 6, 9, and 12 months after the procedure and every 6 months thereafter. If patients were unable to be seen, their status was assessed by a nurse practitioner via the telephone and monitoring tests were obtained by the referring physician. During the first 5 months after the ablation, cardiac event monitoring was used to assess AF recurrence. Patients were asked to transmit their rhythm status 3 times a day and when they experienced symptoms consistent with AF. In addition, 48-hour Holter monitoring was performed at 3, 6, 9, and 12 months and every 6 months thereafter. In June 2007, 48-hour Holter was replaced by 7-day Holter monitoring.

      Statistical analysis

      Continuous data were described as mean ± standard deviation and as counts and percent if categorical. Student's t-test, one-way analysis of variance, χ2-test, and Fisher's exact test were used to compare differences across AF types. Multivariate Cox regression was used for identifying significant predictors of AF recurrence while controlling for clinically relevant covariates. All potential confounders were entered into the model based on known or expected clinical relevance, regardless of their statistical significance. The controlling variables used in the model were age, preprocedure left ventricular ejection fraction (EF), LA size, hypertension, diabetes, coronary artery disease, non-PV trigger, and type of AF. For the purpose of analysis, age was dichotomized into ≤55 and >50 years, and left ventricular EF and LA size were categorized into >50 and ≥40 mm, respectively. Tests were run to examine the presence of any significant interactions and to identify possible multicollinearity of the covariates. The hazard ratio (HR) and 95% confidence interval (CI) of AF recurrence were computed. Recurrence-free survival over time was calculated by Kaplan-Meier method. All tests were two-sided, and P <.05 was considered statistically significant. Analysis was performed using SAS 9.2 (SAS Institute Inc., Cary, NC).

      Results

      Patient characteristics

      Females made up 15.8% of the population (P <.001). The number of females who underwent catheter ablation during the observation period steadily increased from 105 in 2005 to 148 in 2008 (Figure 1). Females were older and had a higher incidence of prior stroke and LSPAF and a lower incidence of diabetes type II and coronary artery disease than males. Female had more non-PV sites of firing than males (261 [50.4%] vs. 449 [16.3%]; P <.001]. Females had failed more antiarrhythmic agents and were referred later for catheter ablation than males (Table 1).
      Figure thumbnail gr1
      Figure 1The yearly prevalence of females who underwent catheter ablation over the course of this study.
      Table 1Patient characteristics (n = 3265)
      FemaleMaleP
      No. of subjects, n (%)518 (15.8)2747 (84.2)<.001
      Statistically significant.
      Age, years59 ± 1356 ± 19<.01
      Statistically significant.
      BMI, kg/m228 ± 827.3 ± 9.54
      Comorbidities, n (%):
       Diabetes type II57 (11)414 (15).016
      Statistically significant.
       Hypertension286 (55.2)1100 (40)<.001
      Statistically significant.
       Coronary artery disease36 (7)312 (11.3).003
      Statistically significant.
       Stroke20 (3.8)45 (1.6)<.001
      Statistically significant.
      Type of AF, n (%):
       Paroxysmal237 (46)1506 (55)<.001
      Statistically significant.
       Persistent atrial140 (28)692 (25).379
       Long-standing persistent141 (27)549 (20)<.001
      Statistically significant.
      Echo parameters:
       Preprocedure EF, %56 ± 849 ± 5<.001
      Statistically significant.
       Preprocedure LA, cm4.3 ± 0.54.6 ± 0.3.04
      Statistically significant.
      No. of failed antiarrhythmic drugs4 ± 12 ± 3.04
      Statistically significant.
      Time from diagnosis to catheter ablation referral, years6.51 ± 74.85 ± 6.5.02
      Statistically significant.
      Follow-up period, in months24.28 ± 16.1535.57 ± 17.75.16
      a Statistically significant.

      Ablation success and complication rates

      After 24 ± 16 months of follow-up, females had lower success rates than males (68.5% vs. 77.5% P <.001). Kaplan-Meier survival estimates for freedom from AF/atrial tachycardia after ablation are shown in Figure 2. Cox regression demonstrated that in female patients, higher body mass index (BMI), non-PAF, and non-PV triggers predicted procedural failure. Females with non-PAF or non-PV triggers were twice as likely to fail catheter ablation (Table 2).
      Figure thumbnail gr2
      Figure 2Kaplan-Meier survival curve showing freedom from AF over the follow-up period of the study.
      Table 2Multivariate Cox regression analysis for recurrence of AF
      Predictors of failureHRLower 95% CIUpper 95% CIP
      Age >501.240.991.56.07
      Diabetes type II1.660.942.94.08
      Hypertension0.740.501.09.13
      BMI >301.111.041.18.001
      Statistically significant.
      Coronary artery disease1.020.422.47.97
      EF >50%1.031.001.06.10
      LA size >40 mm1.060.791.41.71
      AF type (non-PAF)2.071.622.61<.001
      Statistically significant.
      Non-PV triggers2.051.233.39.01
      Statistically significant.
      Note: Non-PV triggers are triggers located outside of the PV antrum.
      a Statistically significant.
      Females had more hematomas (2.1% vs. 0.9%; P =.026) and pseudoaneurysms (0.6% vs. 0.1%; P = .031) than males (Table 3). Adjusted Cox regression showed that type of AF (non-PAF), BMI (>30), and diabetes type II predicted complications in an all-female cohort (Table 4).
      Table 3Incidence of complications secondary to ablation in females and males
      Females (n = 518)Males (n = 2747)P
      Complications, n (%):26 (5)66 (2.4)<.001
      Statistically significant.
       Hematoma11 (2.1)27 (0.9).026
      Statistically significant.
       Moderate to severe PV stenosis6 (1.2)12 (0.4).053
       Stroke4 (0.8)17 (0.6).762
       Pericardial effusion2 (0.4)8 (0.29).665
       Pseudoaneurysm3 (0.6)2 (0.1).031
      Statistically significant.
      a Statistically significant.
      Table 4Adjusted multivariate Cox proportional hazards regression showing predictors of complications in females
      Predictors of complications in femalesHRLower 95% CIUpper 95% CIP
      Age0.920.661.27.60
      Diabetes2.801.395.62.001
      Statistically significant.
      Hypertension1.750.963.15.07
      BMI >301.131.041.23.01
      Statistically significant.
      Coronary artery disease2.110.825.44.12
      EF >50%1.010.971.06.64
      LA size >40 mm1.160.741.84.51
      AF type (non-PAF)0.590.390.89.01
      Statistically significant.
      a Statistically significant.
      Five (0.96%) females died over the course of the study period. None of the patients died due to complications associated with catheter ablation.

      Discussion

      Main findings

      To the best of our knowledge, this is the largest multicenter study to date that has reported the safety and efficacy of catheter ablation for AF in female patients. The main findings of this study were that (1) significantly fewer females than males had undergone catheter ablation in our experience; (2) females who had undergone catheter ablation tended to be older, had a higher prevalence of non-PAF, had failed more antiarrhythmic agents, and were referred later than males; (3) females failed ablation more often; (4) higher BMI, extra non-PV triggers, and type of AF predicted procedural failure in our female cohort; (5) females who had undergone catheter ablation had significantly more non-PV firing sites than males; and (6) female patients had significantly higher bleeding complications.

      Referral patterns in women undergoing catheter ablation of AF

      Over 5 times more males than females have undergone AF ablation in this retrospective multicenter study. Previous studies have also reported gender disparities in the use of innovative or costly cardiovascular technologies. Women have been under-referred for implantable cardioverter-defibrillator implantation, coronary artery bypass graft surgery, and cardiovascular diagnostic testing.
      • Cappato R.
      • Calkins H.
      • Chen S.
      • et al.
      Worldwide survey on the methods, efficacy and safety of catheter ablation for human atrial fibrillation.
      • Ayanian J.Z.
      • Epstein A.M.
      Differences in the use of procedures between women and men hospitalized for coronary heart disease.
      • Wong C.C.
      • Froelicher E.S.
      • Bacchetti P.
      • et al.
      Influence of gender on cardiovascular mortality in acute myocardial infarction patients with high indication for coronary angiography.
      • Hernandez A.F.
      • Fonarow G.C.
      • Liang L.
      • et al.
      Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure.
      • Mahon N.G.
      • McKenna C.J.
      • Codd M.B.
      • et al.
      Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era.
      • Dagres N.
      • Clague J.R.
      • Breithardt G.
      • Borggrefe M.
      Significant gender-related differences in radiofrequency catheter ablation therapy.
      • Forleo G.B.
      • Tondo C.
      • De Luca L.
      • et al.
      Gender-related differences in catheter ablation of atrial fibrillation.
      In our study, females were referred for catheter ablation after having failed more antiarrhythmic agents and after a longer period of time from diagnosis of AF to catheter ablation than males. Dagres et al
      • Dagres N.
      • Clague J.R.
      • Breithardt G.
      • Borggrefe M.
      Significant gender-related differences in radiofrequency catheter ablation therapy.
      also reported that women were referred for atrioventricular node reentrant tachycardia ablation later than males, after a longer duration of symptoms, and after having failed more antiarrhythmic drugs. Forleo et al
      • Forleo G.B.
      • Tondo C.
      • De Luca L.
      • et al.
      Gender-related differences in catheter ablation of atrial fibrillation.
      reported that in a multicenter study, in which 71 females underwent catheter ablation, the mean time of AF before ablation was 60 months in females versus 47 months in males, and while females had a slightly higher number of failed antiarrhythmic agents, it was not statistically significant. We reported a longer interval from diagnosis of AF to ablation and a larger number of failed antiarrhythmic agents than Forleo et al; however, these differences in findings could possibly be due to differences in health care practices.
      • Forleo G.B.
      • Tondo C.
      • De Luca L.
      • et al.
      Gender-related differences in catheter ablation of atrial fibrillation.
      Prior studies have also reported that once women are diagnosed with AF, they are often treated less aggressively than male patients. The reason why fewer female patients are referred for catheter ablation of AF and after a longer time interval than male patients is not completely apparent. It is possible that females tend to complain less and therefore are less likely to be considered for an invasive procedure. Other explanations may include that female patients are more reluctant to undergo an invasive procedure, physician gender bias referral, and child care issues.

      Clinical profile of female patients undergoing catheter ablation for AF

      Forleo et al
      • Forleo G.B.
      • Tondo C.
      • De Luca L.
      • et al.
      Gender-related differences in catheter ablation of atrial fibrillation.
      also reported that female patients undergoing AF catheter ablation were older and had a higher prevalence of diabetes, hypertension, and coronary artery disease and dilated cardiomyopathy than males. In our study, females patients were older and had a higher prevalence of stroke and hypertension than the male patients.

      Predictors for procedural failure

      Forleo et al reported that males and females had similar AF catheter ablation recurrence rates. However, their study only included 77 females. This discrepancy in success rates in our study can be attributed to the larger number nonparoxysmal cases in our female population. In this respect, LSPAF and persistent AF are more difficult to treat irrespective of gender. Moreover, female patients were substantially more likely to have extra non-PV antral triggers, which can be more challenging to treat effectively. As previously shown, age did not predict failure.
      • Corrado A.
      • Patel D.
      • Riedlbauchova L.
      • et al.
      Efficacy, safety, and outcome of atrial fibrillation ablation in septuagenarians.
      • Bhargava M.
      • Marrouche N.F.
      • Martin D.O.
      • et al.
      Impact of age on the outcome of pulmonary vein isolation for atrial fibrillation using circular mapping technique and cooled-tip ablation catheter.
      • Zado E.
      • Callans D.J.
      • Riley M.
      • et al.
      Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in the elderly.
      On the other hand, LSPAF and extra non-PV antrum triggers predicted failure in our study.

      PVAI complications in women

      In our study, females patients tended to have more cases of hematoma and pseudoaneurysm. When multivariate analysis was performed, higher BMI was found to be a predictor for bleeding complications. However, obesity was not limited to female patients alone. Additionally, there was no statistical difference in BMI between the male and female populations. Another possible cause of the larger number of hematomas in female patients can be attributed to anatomical variations in the relationship of the femoral vein to the artery. In females, the femoral artery and circumflex branches run very close and often overlap the femoral vein, increasing the risk of inadvertent arterial puncture.
      • Siddharth P.
      • Smith N.
      • Mason R.
      • et al.
      Variational anatomy of the deep femoral artery.
      • Hughes P.
      • Scott C.
      • Bodenham A.
      Ultrasonography of the femoral vessels in the groin: implications for vascular access.

      Limitations

      (1) Our study is retrospective in nature and is thereby subject to all the limitations inherent to this study design. However, all data was prospectively collected. (2) Transient recurrence of AF may be undetected if it occurred during a period in which patients were not monitored.

      Conclusion

      Over 5 times more males than females had undergone AF ablation in our catheter ablation experience. Overall, females had lower procedural success rates and higher risk of bleeding complications than their male counterparts. Higher procedural failure rates in female patients can possibly be attributed to a higher prevalence of nonparoxysmal AF, extra non-PV triggers, and a longer history of AF before being considered for ablation, which may have resulted in increased electrical and structural remodeling.

      References

        • Benjamin E.J.
        • Wolf P.A.
        • D'Agostina R.B.
        • et al.
        Impact of atrial fibrillation on the risk of death: the Framingham Heart Study.
        Circulation. 1998; 98: 946-953
        • Rienstra M.
        • Van Veldhuisen D.J.
        • Hagens V.E.
        • et al.
        Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) Study.
        J Am Coll Cardiol. 2005; 46: 1298-1306
        • Humphries K.H.
        • Kerr C.R.
        • Connolly S.J.
        • et al.
        New-onset atrial fibrillation: sex differences in presentation, treatment and outcome.
        Circulation. 2001; 103: 2365-2370
        • Calkins H.
        • Brugada J.
        • Packer D.L.
        • et al.
        HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up.
        Heart Rhythm. 2007; 6: 816-861
        • Arruda M.
        • Mlcochova H.
        • Prasad S.K.
        • et al.
        Electrical isolation of the superior vena cava: an adjunctive strategy to pulmonary vein antrum isolation improving the outcome of AF ablation.
        J Cardiovasc Electrophysiol. 2007; 18: 1261-1266
        • Kanj M.H.
        • Wazni O.
        • Fahmy T.
        • et al.
        Pulmonary vein antral isolation using an open irrigation ablation catheter for the treatment of atrial fibrillation: a randomized pilot study.
        J Am Coll Cardiol. 2007; 49: 1634-1641
        • Bhargava M.
        • Di Biase L.
        • Mohanty P.
        • et al.
        Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: results from a multicenter study.
        Heart Rhythm. 2009; 6: 1403-1412
        • Nademanee K.
        • McKenzie J.
        • Kosar E.
        • et al.
        A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate.
        J Am Coll Cardiol. 2004; 43: 2044-2053
        • Cappato R.
        • Calkins H.
        • Chen S.
        • et al.
        Worldwide survey on the methods, efficacy and safety of catheter ablation for human atrial fibrillation.
        Circulation. 2005; 111: 1100-1105
        • Ayanian J.Z.
        • Epstein A.M.
        Differences in the use of procedures between women and men hospitalized for coronary heart disease.
        N Engl J Med. 1991; 4: 221-225
        • Wong C.C.
        • Froelicher E.S.
        • Bacchetti P.
        • et al.
        Influence of gender on cardiovascular mortality in acute myocardial infarction patients with high indication for coronary angiography.
        Circulation. 1997; 96: II51-II79
        • Hernandez A.F.
        • Fonarow G.C.
        • Liang L.
        • et al.
        Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure.
        JAMA. 2007; 298: 1525-1532
        • Mahon N.G.
        • McKenna C.J.
        • Codd M.B.
        • et al.
        Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era.
        Am J Cardiol. 2000; 85: 921-926
        • Dagres N.
        • Clague J.R.
        • Breithardt G.
        • Borggrefe M.
        Significant gender-related differences in radiofrequency catheter ablation therapy.
        J Am Coll Cardiol. 2003; 42: 1103-1107
        • Forleo G.B.
        • Tondo C.
        • De Luca L.
        • et al.
        Gender-related differences in catheter ablation of atrial fibrillation.
        Europace. 2007; 9: 613-620
        • Corrado A.
        • Patel D.
        • Riedlbauchova L.
        • et al.
        Efficacy, safety, and outcome of atrial fibrillation ablation in septuagenarians.
        J Cardiovasc Electrophysiol. 2008; 19: 807-811
        • Bhargava M.
        • Marrouche N.F.
        • Martin D.O.
        • et al.
        Impact of age on the outcome of pulmonary vein isolation for atrial fibrillation using circular mapping technique and cooled-tip ablation catheter.
        J Cardiovasc Electrophysiol. 2004; 1: 8-13
        • Zado E.
        • Callans D.J.
        • Riley M.
        • et al.
        Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in the elderly.
        J Cardiovasc Electrophysiol. 2008; 19: 621-626
        • Siddharth P.
        • Smith N.
        • Mason R.
        • et al.
        Variational anatomy of the deep femoral artery.
        Anatom Rec. 1985; 212: 206-209
        • Hughes P.
        • Scott C.
        • Bodenham A.
        Ultrasonography of the femoral vessels in the groin: implications for vascular access.
        Anaesthesia. 2000; 55: 1198-1202