2.2 Patterns of atrial fibrillation and ablation
Paroxysmal AF was more frequent in women than in men (69.0% vs. 56.2%,p <0.001). No statistical significance was noted in the
redo procedure between women and men (13.2% vs 13.1%, p =0.837).
The proportion of patients undergoing cryoablation was similar between
men and women (1.3% vs. 1.1%, p =0.252).
2.3 Comorbidities of atrial fibrillation between sexes
Hypertension was the most common comorbidity in patients. The percentage
of patients with hypertension was higher in women than in men (58.1%
vs. 48.5%, p<0.001). We observed a significant increase in
rate of hypertension in men and women over time. Compared with men,
women were more likely to have a comorbid diagnosis of heart failure,
hyperlipemia, congenital heart disease, hyperthyroidism, hypothyroidism
and cancer (p <0.05) (Table 1). Dilated cardiomyopathy
(DCM) was more frequent in male patients (0.6% vs. 0.1%)
(p <0.001). The incidence of thromboembolic events such
as stroke and TIA were comparable between men and women
(p =0.524). Increased temporal trends of heart failure,
hypertension, stroke, and vascular diseases were observed in both sexes
(Table 2).
2.4 The temporal trends of CHA2DS2-VA
score between sexes
The
CHA2DS2-VA score was higher in women
than in men (1.64 vs. 1.28, p <0.001). The temporal
trend in the score increased in women from 1.17 to 1.81
(p<0.001) and in men from 0.91 to 1.41
(p <0.001); the sex gap in
CHA2DS2-VA score did not narrow over
time. The percentage of patients with
CHA2DS2-VA score ≥2 was higher in women
than in men (49.8% vs. 35.8%, p <0.001), and the
temporal trend of this sex gap was enlarged (8.0% in 2005-2007 vs.
15.5% in 2017-2019, p =0.03, Figure 3).
Discussion
In this retrospective study with a large cohort of 20215 cases from a
single center, we evaluated the sex differences and temporal trends in
hospitalization for catheter ablation of non-valvular atrial
fibrillation for 15 years. We observed that (1) the number of women was
almost half of that of men, the numbers of men and women significantly
increased over time, and the
temporal trend in the man/woman ratio did not change substantially; (2)
the median time of in-hospital stay and the in-hospital mortality were
comparable between women and men; (3) women were five years older than
men and had more comorbidities; and (4) the
CHA2DS2-VA score was higher in the women
compared with men. The percentage of patients with
CHA2DS2-VA score ≥2 increased more
quickly in women than in men.
Sex differences in AF ablation has gained increased interest. The safety
of AF ablation is always the greatest concern for the sex difference.
Several studies demonstrated that women were more likely to have a
procedural complication compared with men. Kaiser et al. reported that
women had a high risk of vascular complication, hemorrhage, and cardiac
tamponade compared with men during the procedure.8Data from the Chinese Atrial Fibrillation Registry also showed that
women had more vascular complications.9 In the present
study, we focused on in-hospital
mortality, which was 0.06% for both men and the women and did not
significantly change during the study period. An initial study by
Cappato et al. showed a risk of AF ablation–related mortality of 1 per
1000 patients.10 In a real-world setting, Deshmukh et
al. reported that the in-hospital mortality of AF ablation for all US
hospitals was 0.42% between 2000 and 2010.11 However,
these two studies did not provide sex-specific mortality rates.
In-hospital mortality in the present study is much lower than in
previous studies. It is well known that the complication and the
mortality of AF ablation are associated with the operator’s experience
and hospital volume. In line with this issue, data from Cleveland Clinic
showed zero procedure-related deaths over 16 years.12Therefore, our data may be representative of experienced AF ablation
centers in the real world. Intriguingly, the in-hospital stay time was
gradually shortened during the study period in both sexes. In 2019, the
average length of in-hospital stay was 4.3 ± 2.4 and 4.5 ± 2.6 days for
the men and the women, respectively. AF ablation is the most common
complicated ablation procedure, and there are challenging issues related
to pre-procedural, periprocedural and post-procedural management. The
progress of ablation device technology and ablation strategies, as well
as the operator’s experience, has substantially enhanced the safety,
efficacy, and efficiency of AF ablation. Consequently, the
life-threatening complications, procedural duration, and in-hospital
stay time have been significantly improved. In experienced AF centers,
even same-day discharge after AF ablation is feasible in the majority of
patients.13 Despite the lack of data about
life-threatening complications of AF ablation in the present study, the
same in-hospital mortality and the same hospital stay time between men
and women suggested that excellent safety during the ablation procedure
was indiscriminately provided for both sexes.
AF ablation has been the primary clinical service in many arrhythmia
centers. The number of AF ablation cases has substantially increased in
recent decades. Sharp increases in cases in the present study were noted
in both sexes, and the temporal trend in the man/woman ratio did not
significantly change. Our data were consistent with a nationwide cohort
study from Denmark, in which the number of patients undergoing AF
ablation almost tripled from 2005 to 2014, the majority of the patients
were men, and the man/woman ratio remained constant over the study
duration.14 A study using Quebec administrative
databases also demonstrated that the patients with AF undergoing AF
ablation increased almost seven-fold in 10 years, and the annual
proportion of women in the AF ablation cohort had not surpassed
30%.15 All the data support the finding that there
has been no increase in the relatively low percentage of women
undergoing AF ablation despite expansion of the uptake of AF ablation.
Two large cross-sectional studies of Chinese cohorts reported that
age-adjusted prevalence of AF was similar in women and men, implying
that women with AF are less likely to be referred for the advanced
therapy of ablation than men in China.16,17
For the direct comparison of the disease severity and complexity between
men and women, the CHA2DS2-VA score
(excluding female sex) was used in the present study. Our data showed
that this score was higher in women than men, and more women had scored
≥2 than men. Older age and more comorbidities in women accounted for
this sex gap. Our study is consistent with previous studies. For
instance, a study from Europe showed that the women undergoing catheter
ablation for drug-refractory AF were older, had a long history of AF,
and were more likely to have hypertension and valvular
disease.18 Intriguingly, the
CHA2DS2-VA score increased in both sexes
from 2005 to 2019 in the present study. An epidemiological study from
South Korea showed that there was a significant increase in the
proportion of high CHA2DS2-VASc scores
(≥2) in patients with AF from 2008 to 2015.19 There is
no data on CHA2DS2-VASc score trends in
China. Since the prevalence of AF in East Asia is similar and lower than
that in Western countries, we speculated that the temporal trend in
CHA2DS2-VA score in the present study is
unlikely to reflect the score shifting in the general AF population. The
expansion of indication for AF ablation in the recent decade and
improvements in the operator’s experience are attributable to the
temporal trend in this score.
Moreover, the temporal trend in the sex gap of the
CHA2DS2-VA score did not narrow, and
instead showed an increasing tendency. Especially, in the patients with
CHA2DS2-VA score ≥2, our data clearly
showed that this sex gap became wider over time, suggesting a decrease
in sex disparity in AF ablation over time. To our best of knowledge, no
previous study investigated this issue. In a study of questionnaire
measure, women often reported greater AF severity, frequency, and burden
than men.20 Consequently, female AF patients tended to
be more symptomatic and may have been more likely to seek medical
attention as a result. A study by Bhave et al. showed that
the sex disparity in AF management
resulted in less referrals for advanced therapies in
women.21 Previous work has suggested that fewer women
access new technology services, such as smaller devices and less
invasive procedures. For example, women were also less likely to undergo
cardiac catheterization, percutaneous transluminal coronary angioplasty,
coronary artery bypass surgery, pacemaker and defibrillator
implantation, compared to men.22-24 Hence, the
apparent impact of sex disparity is that women who do undergo AF often
have more comorbidities and older age. Despite the finding that efficacy
and safety of catheter ablation for AF in the hospital were comparable
in women and men in the present study, less favorable outcomes of AF
ablation have been reported in women, such as more AF recurrence and
more rehospitalization after the procedure. Compelling evidence
demonstrates that earlier AF detection and ablation enhance
efficacy.25,26 We speculate that the sex differences
in hospitalization for AF ablation are attributable to the adverse
clinical outcomes in women. The temporal trends of large gaps between
sexes in the hospitalization for AF ablation raise a warning flag to
resolve this issue.
The reasons for the sex
differences in the hospitalization for AF ablation remain unknown.
Sex-related differences of biology or physiology cannot explain the sex
differences observed in the present study. Socio-economic inequalities
between women and men need to be taken into account.27The sex inequalities in individual incomes and education level likely
greatly contribute to this issue. Further investigation to determine the
reasons for the sex differences in the hospitalization for AF ablation
is warranted.
The study has several limitations. First, it is a study from one of the
largest arrhythmia centers in China and is therefore limited by
selection bias. However, it may represent a developing trend of AF
ablation in China. Second, the information about periprocedural
complications and the follow-up is lacking. We cannot further evaluate
the differences and trends in the safety and efficacy of AF catheter
ablation between women and men.
Conclusions
The present study evaluated the sex differences and temporal trends of
hospitalization for catheter ablation of AF from one of the largest
arrhythmia centers in China. Efficacy and safety of catheter ablation
for AF were comparable between women and men. However, the women showed
a higher CHA2DS2-VA score compared with
the men. The percentage of patients with
CHA2DS2-VA score ≥2 increased more
quickly in women than men. The reasons for sex differences in the
hospitalization for AF ablation remain unknown. Further sex-specific
research is warranted to solve this issue.
DISCOLOSE
None.
ACKNOLEGEMENTS
This work was supported by the National Key Research and Development
Program of China (Grant Nos. 2018YFC1312501, 2016YFC0900901), the
National Science Foundation of China (Grant Nos. 81870244, 81670291 and
81770318) and Beijing Natural Science Foundation, China (Grant Nos.
7192051).
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Table 1. Baseline characteristics of AF patients by gender