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\begin{document}

\title{The burden of premature ventricular contractions predicts adverse fetal
and neonatal outcomes among pregnant women without structural heart
disease: a prospective cohort study}



\author[1]{Jing Lin}%
\author[1]{Yanxia Qian}%
\author[1]{Qiushi Chen}%
\author[1]{Mingming Zhang}%
\author[1]{Jiahui Zhang}%
\author[2]{Yaoxi Chen}%
\author[2]{Ruijie Xu}%
\author[2]{Jingxian Chen}%
\author[2]{Yukang Shi}%
\author[2]{Shunxin Yang}%
\author[2]{Xinyi Luo}%
\author[1]{Qiang Ding}%
\author[1]{Xin Wu}%
\author[1]{Junhong Wang}%
\affil[1]{Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital}%
\affil[2]{Nanjing Medical University}%


\vspace{-1em}



  
  \date{May 07, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To investigate the outcomes of fetuses or neonates of
pregnant women with premature ventricular contractions (PVCs). Design:
Prospective cohort study. Setting: University-affiliated tertiary
hospital. Population: 6, 148 pregnant women with normal cardiac
structure and function and 103 with a PVC burden \textgreater{}0.5\%
among them. Methods: 103 pregnant women with PVCs were divided into two
groups based on the presence or absence of adverse fetal or neonatal
events. The adverse outcomes were compared between the groups. Main
outcome measures: Adverse fetal and neonatal events: premature birth
(\textless{}37 weeks gestation), small-for-gestational-age birth weight
(\textless{}10th percentile for gestational age or \textless{}2500 g),
respiratory distress syndrome, intraventricular hemorrhage and fetal
death (after 20 weeks gestation and before birth). Results: A total of
17 adverse events (12 cases) occurred among 103 pregnant women with
PVCs, which was significantly higher than that among women without PVCs
(11.65\% vs. 2.93\%, p\textless{}0.01). Compared with that of the women
without adverse events, the median PVC burden of women with adverse
fetal or neonatal outcomes was significantly higher (9.02\% vs. 2.30\%,
p\textless{}0.01). Multivariate logistic regression analysis
demonstrated that PVC burden was associated with adverse fetal or
neonatal outcomes among pregnant women with PVCs (OR: 1.34, 95\% CI
(1.11-1.61), p\textless{}0.01). Conclusions: Frequent PVCs have adverse
effects on pregnancy, and the PVC burden might be an important factor
associated with adverse fetal and neonatal outcomes among pregnant women
with PVCs. Our cohort study indicated that the higher the PVC burden is,
the higher the likelihood of adverse events would be.%
\end{abstract}%



\sloppy


\textbf{The burden of premature ventricular contractions predicts
adverse fetal and neonatal outcomes among pregnant women without
structural heart disease: a prospective cohort study}

\textbf{short title: PVCs in pregnancy}

Jing Lin \textsuperscript{a\#}, Yanxia Qian \textsuperscript{a\#},
Qiushi Chen \textsuperscript{a\#}, Mingming Zhang \textsuperscript{a},
Jiahui Zhang \textsuperscript{a}, Yaoxi Chen \textsuperscript{b}, Ruijie
Xu \textsuperscript{b}, Jingxian Chen \textsuperscript{b}, Yukang
Shi\textsuperscript{b}, Shunxin Yang \textsuperscript{b}, Xinyi
Luo\textsuperscript{b}, Qiang Ding \textsuperscript{c}, Xin
Wu\textsuperscript{d*}, Junhong Wang \textsuperscript{a,e*}

\textsuperscript{a} Department of Cardiology, the first affiliated
hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu,
China

\textsuperscript{b} Nanjing Medical University, Nanjing, 210009,
Jiangsu, China

\textsuperscript{c} Department of Breast Surgery, the first affiliated
hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu,
China

\textsuperscript{d} Department of Obstetrics, the first affiliated
hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu,
China

\textsuperscript{e} State Key Laboratory of Natural Medicines, China
Pharmaceutical University, Nanjing, 210009, Jiangsu, China

\# These authors contributed equally to the work.

*Correspondence to Xin Wu, MD, Department of Obstetrics, the First
Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300,
Nanjing 210029, China. E-mail:\emph{wuxin0220@aliyun.com} and Junhong
Wang, MD, PhD, Department of Cardiology, the First Affiliated Hospital
with Nanjing Medical University, Guangzhou Road 300, Nanjing 210029,
China. E-mail:

\emph{wangjunhong@jsph.org.cn}

Total word count: 2155

Abstract

Objective: To investigate the outcomes of fetuses or neonates of
pregnant women with premature ventricular contractions (PVCs).

Design: Prospective cohort study.

Setting: University-affiliated tertiary hospital.

Population: 6, 148 pregnant women with normal cardiac structure and
function and 103 with a PVC burden \textgreater{}0.5\% among them.

Methods: 103 pregnant women with PVCs were divided into two groups based
on the presence or absence of adverse fetal or neonatal events. The
adverse outcomes were compared between the groups.

Main outcome measures: Adverse fetal and neonatal events: premature
birth (\textless{}37 weeks gestation), small-for-gestational-age birth
weight (\textless{}10th percentile for gestational age or
\textless{}2500 g), respiratory distress syndrome, intraventricular
hemorrhage and fetal death (after 20 weeks gestation and before birth).

Results: A total of 17 adverse events (12 cases) occurred among 103
pregnant women with PVCs, which was significantly higher than that among
women without PVCs (11.65\% vs. 2.93\%, p\textless{}0.01). Compared with
that of the women without adverse events, the median PVC burden of women
with adverse fetal or neonatal outcomes was significantly higher (9.02\%
vs. 2.30\%, p\textless{}0.01). Multivariate logistic regression analysis
demonstrated that PVC burden was associated with adverse fetal or
neonatal outcomes among pregnant women with PVCs (OR: 1.34, 95\% CI
(1.11-1.61), p\textless{}0.01).

Conclusions: Frequent PVCs have adverse effects on pregnancy, and the
PVC burden might be an important factor associated with adverse fetal
and neonatal outcomes among pregnant women with PVCs. Our cohort study
indicated that the higher the PVC burden is, the higher the likelihood
of adverse events would be.

Key words: fetal/neonatal outcomes; pregnancy; premature ventricular
contractions (PVCs)

Tweetable abstract: The PVC burden might be the main factor associated
with adverse pregnancy outcomes.

Funding

This work was supported by the National Natural Science Foundation of
China (NSFC 81570328, Wang JH), the Jiangsu Province ''333'' project
(BRA2018389, Wang JH), the Jiangsu Province's Key Provincial Talents
Program (ZDRCB2016005, Wang JH), the Open Project of State Key
Laboratory of Natural Medicines (No. SKLNMKF201903, Wang JH) and the
International cooperation project of Jiangsu Province (BZ2018054, Ding
Q).

Introduction

Idiopathic PVCs are relatively benign in cases without structural heart
diseases but may signal an increased risk of sudden death in cases with
structural heart disease (SHD) and may be markers of underlying
pathology. An estimated prevalence of 1 to 4\% is found in the general
population on standard 12-lead electrocardiography
(ECG)\textsuperscript{1}. Frequent PVCs, defined as more than 10\% of
all QRS complexes on standard 24-hour Holter monitoring, have been found
to be associated with subsequent development of left ventricular
dilatation and PVC-induced cardiomyopathy. Treatment of frequent PVCs in
patients with impaired ventricular function can reverse this
pattern\textsuperscript{2-7}. PVCs may increase during pregnancy, which
leads to an additional challenge, as pregnancy outcome implications are
not known for this already cardiac overloaded
state\textsuperscript{8,9}. Relatively few studies have evaluated the
relationship between PVCs and the adverse outcomes of fetuses or
neonates\textsuperscript{10}. Therefore, we aimed to determine the
relationship between the adverse outcomes of the fetus or neonate among
pregnant women with PVCs.

Methods

Study design and patient population

This is a single-center prospective cohort study of consecutive
pregnancies referred to the First Affiliated Hospital of Nanjing Medical
University from July 2017 to July 2019. The inclusion criteria were
pregnant women with normal cardiac structure and function based on
echocardiographic examination. Pregnant women with PVC burdens greater
than 0.5\% on Holter examination each time during the whole pregnancy
period were classified as the PVC group. The exclusion criteria were as
follows: pregnant women with 1) hyperthyroidism, 2) hypothyroidism, 3)
gestational hypertension or pregnancy with hypertension, 4) type I or II
diabetes, 5) chronic nephritis or impaired renal function (creatinine
clearance rate, Ccr \textless{}60 ml/min), 6) autoimmune disease, 7)
congenital heart diseases, 8) pulmonary artery hypertension, 9)
cardiomyopathy, 10) alcohol abuse, 11) anemia (Hgb\textless{}110 g/l),
12) smoking, and 13) a family history of sudden cardiac death. The study
protocol was performed in accordance with the ethical standards
established in the 1964 Declaration of Helsinki and its later amendments
and was approved by the institutional ethics committee of the First
Affiliated Hospital of Nanjing Medical University (2019SR-503). Informed
consent was obtained from all pregnant women enrolled in the study.

Baseline characteristics

Clinical and 12-lead electrocardiogram (ECG) data were collected at the
time of the initial clinic visit or for routine obstetric examinations
during the first trimester of pregnancy. If the standard 12-lead ECG
recorded the PVC events, Holter monitoring was then performed and
reexamined in each subsequent trimester to assess the burden of
ventricular premature contractions and analyze the total number of QRS
complexes, total number of PVCs and total runs of nonsustained
ventricular tachycardia (NSVT) (run with \textgreater{}3 consecutive
PVCs but \textless{}30 s). Furthermore, if the women had self-reported
symptoms such as palpitation during pregnancy, the 12-lead ECG
examination was then performed. If no arrhythmia was recorded, a
wearable single-lead ECG recorder (Shuweikang company, Nanjing, China)
was then weared for 3 continuous days to record the possible PVC events
in those pregnant women. The single-lead wearable ECG recorder was
designed to recognize the arrhythmia based on the Convolutional Neural
Network (CNN) technology. It can easily identify the PVCs when it
happens. Here is the image of the wearable ECG recorder and the
representative PVC captured by the recorder (Figure S1). And if the PVCs
was documented by 12-lead ECG or the wearable single-lead ECG recorder
and confirmed by the ECG experts in our center (Lin J \& Chen QS), the
Holter was examined thereafter once a trimester for the remainder of the
pregnancy period. The average PVC burden was determined by calculating
the total number of PVCs in the total QRS complexes. PVC morphological
patterns were analyzed to determine the PVC origin. PVCs with inferior
axis and left bundle branch block (LBBB) patterns were determined to
most likely originate from the right ventricular outflow tract (RVOT).
Specific diagnostic procedures were carried out with reference to
published diagnostic criteria\textsuperscript{11}. Specifically, the
burden, morphology and the origin of PVCs were calculated not by the
wearable recorder but by the Holter and 12-lead ECG results due to its
single lead characteristics.

Echocardiography was performed in the first and third trimesters in all
pregnant women. Experienced echocardiographers performed
echocardiography to ensure that there was no evidence of SHD in the
pregnant women and to ensure that the cardiac function of the enrolled
pregnant women was within the normal range (left ventricular ejection
function (LVEF) \textgreater{}60\%).

All pregnant women were followed, and the data on characteristics
including age, comorbid medical conditions and family history were
recorded. All women were followed from preconception to 1 week after
delivery. If the exclusion criteria were met, they were excluded from
the study.

Neonatal/fetal outcome events

Two physicians blinded to the women's baseline characteristics
independently verified adverse events. Adverse fetal and neonatal events
were defined as previously described\textsuperscript{12}: premature
birth (\textless{}37 weeks gestation), small-for-gestational-age birth
weight (\textless{}10th percentile for gestational age or
\textless{}2500 g), respiratory distress syndrome, intraventricular
hemorrhage and fetal death (after 20 weeks gestation and before birth).
Only one event was counted if multiple events occurred in the fetus or
newborn simultaneously.

Statistical analysis

Statistical analysis was performed using SPSS (Version 22.0). Data are
presented as the means \selectlanguage{ngerman}± SDs, medians (25th--75th percentiles), or
proportions. Student's t-test or the Wilcoxon rank-sum test was used to
compare continuous variables between the women with and without adverse
fetal/neonatal events who had PVCs \textgreater{}0.5\%. Possible risk
factors of adverse events were analyzed using univariable logistic
regression, followed by multivariable logistic regression. A P value
\textless{}0.05 was considered statistically significant.

Results

Baseline characteristics and fetal or neonatal outcomes

6, 148 pregnant women who fulfilled the inclusion criteria were enrolled
consecutively, of which 103 had symptomatic or asymptomatic PVCs. A
total of 17 adverse events occurred in 103 pregnant women with PVCs,
including 5 cases of respiratory distress syndrome, 5 preterm births and
7 small-for-gestational-age births. Finally, only 12 women with adverse
events were counted, as multiple events occurred in some of them
simultaneously. The remaining defined adverse events did not occur. The
other 91 pregnant women with PVCs delivered safely~without adverse
events. A total of 177 fetal and neonatal adverse cases were counted in
the cohort of 6,045 pregnant women without PVCs. The incidence of
adverse events was significantly higher in PVC cases (11.65\%) than in
those without PVC (2.93\%) (Figure 1).

Cardiac rhythm of pregnant women with PVCs

The pregnant women with PVCs were divided into two groups on the basis
of the presence or absence of adverse events. The baseline
characteristics are listed in Table 1. The proportion of bigeminy PVCs
was significantly higher in pregnant women with adverse fetal or
neonatal outcomes (50\% vs. 19.8\%, p\textless{}0.05), as was the median
PVC burden, than in women without adverse events (9.02\% vs. 2.30\%,
p\textless{}0.01). The median documented PVC burden was 2.84\% (1.02\%
to 6.10\%). Eight pregnancies had a maximal PVC burden
\textgreater{}10\%, and of these, 2 pregnancies had a PVC burden
\textgreater{}20\%. Although the LVEF of the adverse outcome group was
within the normal range, it remained slightly lower than that of the
control group (64.16±1.56\% vs. 65.69±2.54\%, p\textless{}0.05). There
were no other significant differences in the remaining baseline data
between the two groups.

12-Lead ECG showed normal sinus rhythm with premature ventricular
complexes in the study. PVCs with an LBBB and inferior axis, most likely
originating from RVOT, were found in 41.75\% of pregnancies with PVCs.
In contrast, PVCs with an RBBB and inferior axis, frequently associated
with the left ventricular outflow tract (LVOT), accounted for
approximately 11.65\%, far less than PVCs associated with the RVOT.
According to the special morphology of PVCs reported in the previous
literature\textsuperscript{12-15}, PVCs originating from the tricuspid
annulus account for approximately 12.62\% and 20.39\% of PVCs
originating from the papillary muscles or fascicle of the left
ventricle, respectively. A total of 9.71\% of PVC origins could not be
determined from the ECG (Figure S2).

Predictors of fetal and neonatal outcomes

The baseline characteristics of the study cohort suggested that the
average burden of PVCs was related to adverse outcomes, so the burden of
PVCs was further divided into low (\textless{}33rd percentile), middle
(33rd-67th percentile) and high groups (\textgreater{}67th percentile)
according to the percentile of the average PVC burden (Figure 2). The
incidence of adverse events was significantly higher in the high-burden
PVC group than in the low and middle groups, indicating that the higher
the PVC burden, the higher the likelihood of adverse events would be.

Univariable logistic regression analysis demonstrated that the LVEF,
bigeminy and burden of PVCs were associated with adverse fetal or
neonatal outcomes among pregnant women with PVCs; however, statistical
significance was evident for PVC burden only in the multivariate
logistic regression analysis (OR: 1.34, 95\% CI (1.11-1.61),
p\textless{}0.05, Table 2).

\subsubsection*{}

{\label{section}}

\subsubsection*{Discussion}

{\label{discussion}}

\subsubsection*{Main Findings}

{\label{main-findings}}

It is widely recognized that idiopathic PVCs are relatively benign in
structurally normal hearts\textsuperscript{16}; however, relatively few
studies have evaluated the relationship between PVCs and the adverse
outcomes of fetuses or neonates among pregnant women\textsuperscript{10,
17}. In this study, we found that PVCs were associated with a higher
frequency fetal/neonatal adverse events among pregnant women with a
structurally normal heart. In fact, we further demonstrated that `high'
PVC burden is an important factor for predicting the incidence of
adverse fetal/neonatal outcomes.

Interpretation

In our study, the pregnant women had a structurally normal heart and
high PVC burden, and the rate of adverse fetal/neonatal cases was
11.65\%. However, in the group of women without PVCs, the incidence rate
was only 2.93\%, which was significantly lower than that previously
reported in the group of pregnant women with or without structural heart
disease\textsuperscript{10, 18}. The reasons might be that comorbidities
that may cause adverse fetal/neonatal outcomes, such as diabetes,
hypertension or hyperthyroidism were excluded from our study. In fact,
when the pregnant women with PVCs were divided by outcome, a
significantly high PVC burden, a high rate of bigeminal PVCs and
slightly decreased LVEF were associated with a high incidence of
fetal/neonatal events. Further multivariate logistic analysis suggested
that a high PVC burden was the only predictor of adverse fetal/neonatal
outcomes among women with PVCs. In contrast to previous
reports\textsuperscript{10}, our study revealed a close relationship
between PVCs and adverse fetal/neonatal outcomes among pregnant women,
suggesting that more active medication or even invasive strategies such
as radiofrequency ablation should be considered for women with a high
PVC burden before or during pregnancy\textsuperscript{19}. Furthermore,
it is undeniable to say that some of pregnant women with PVCs would not
be captured through an intermittent screening 12-lead EKG, which may
cause misclassification of women with PVCs into those without PVCs. We,
therefore, use the wearable single-lead ECG recorder to identify the
possible PVC in those women with self-reported symptoms such as
palpitation to reduce the possible misclassification.

Idiopathic PVCs are distributed mainly to specific cardiac structural
sites, of which the RVOT accounts for approximately 67\%, and the rest
are mainly followed by the LVOT around the annulus, papillary muscles
and other special sites\textsuperscript{20}. The distribution of the
origin of PVCs in all pregnant women was documented to investigate the
relationship between the origin of PVCs and adverse pregnancy outcomes.
Unlike the studies by Nakagawa et al\textsuperscript{9} and Tong et
al\textsuperscript{10}, which reported that 73\%\textasciitilde{}92\% of
PVCs originated from RVOT in pregnant women, we found that approximately
57.28\% of PVCs originated from the right ventricle, of which only
41.75\% originated from the RVOT. In addition, PVCs of the left
ventricle accounted for approximately 32.04\% in our study, which was
significantly higher than that in the normal population. The possible
mechanism may be the reason that the left ventricle is more sensitive to
volumetric load than the right ventricle. However, because the origin of
9.71\% of PVCs could not be identified based on the 12-lead ECG in our
study, this may have an impact on classification of the true
distribution of PVCs in pregnant women.

Study limitations

Although this study is a prospective, single-center study, the number of
participants included is still relatively small; therefore, a
large-scale and multicenter study should be performed in the future.
Second, PVC origin was classified by a standard 12-lead ECG pattern in
the study. Undeniably, changes in diaphragm position during pregnancy
and cardiac rotation may cause misjudgment of the origin of PVCs. Third,
because the PVC burden may fluctuate throughout the day and throughout
stages of pregnancy, we applied the average PVC burden screened by
Holter in each trimester to represent the PVC burden during pregnancy.
It is therefore suggested to use long-term wearable monitoring equipment
to screen the PVC burden in the future. Finally, all patients underwent
only two-dimensional echocardiography in the study, and cardiac magnetic
resonance might be suitable for further study to eliminate the
possibility of latent cardiomyopathy.

Conclusions

In conclusion, our study revealed that the prevalence of PVCs in
pregnancy is higher than that in the normal population. Frequent PVCs
have adverse effects on pregnancy, and the PVC burden might be the main
factor associated with adverse pregnancy outcomes.

Disclosure of interests

The authors have declared that no conflict of interest exists.

Contribution to authorship

WJH, WX: Designed, supervised the study and prepared the manuscript. LJ,
QYX, CQS: Data collection and analysis, writing original draft. CYX,
XRJ, CJX, SYK, YSX and LXY: Data collection and analysis. ZMM and ZJH:
Writing - Review and Editing. DQ: Project administration and data
analysis.

Details of ethics approval

The study protocol was performed in accordance with the ethical
standards established in the 1964 Declaration of Helsinki and its later
amendments and was approved by the institutional ethics committee of the
First Affiliated Hospital of Nanjing Medical University (2019SR-503).

Supporting Information

Additional supporting information may be found online in the Supporting
Information section at the end of the article.

Figure S1. The image of the wearable one-lead ECG recorder and
representative PVC recorded by the recorder. A\&B: the cover and back
image of the recorder; C: the representative PVC recorded by the
recorder.

Figure S2. The origin of PVC in pregnant women. LVOT, left ventricular
outflow tract; RVOT, right ventricular outflow tract; TV, tricuspid
valve; LP, left posterior; LA, left anterior; others indicate 10
unidentified classifications, 1 from right ventricular inflow tract, 1
from right ventricular apex, 1 from His bundle and 1 from right
ventricular mid-septum.

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Table 1\selectlanguage{english}. Baseline characteristics of pregnant women with premature
ventricular contractions\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Characteristic\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
No adverse events (n=91)\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Adverse events (n=12)\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
P value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Age, y\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
30.46\selectlanguage{ngerman}±4.62\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
32.67\selectlanguage{ngerman}±5.55\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.132\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Previous abortion(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
32(35.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5(41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.752\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
ECG\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
V-Bigeminy(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18(19.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6(50.0)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.030\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Multifocal PVC(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2(2.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2(16.7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.066\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
NSVT(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1(1.1)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0(0)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.000\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Origin\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
LV(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28(30.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5(41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.515\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
PVC burden(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.30(0.88,4.85)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.02(7.43,11.71)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.000\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
LVEF\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
65.69\selectlanguage{ngerman}±2.54\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
64.16\selectlanguage{ngerman}±1.56\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.032\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Childbirth type\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Natural childbirth(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
55(60.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5(41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.351\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are expressed as mean\selectlanguage{ngerman}±SD, medians (25th--75th percentiles), or
number (percentage). ECG, electrocardiogram; PVC, premature ventricular
contraction; NSVT, non-sustained ventricular tachycardia; LV, left
ventricular; LVEF, left ventricular ejection fraction

Table 2\selectlanguage{english}. Logistic regression analysis for adverse events in pregnant
women with PVCs\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& Univariable analysis OR (95\% CI) & Univariable analysis OR (95\% CI)
& Univariable analysis OR (95\% CI) & Multivariable analysis OR (95\%
CI) & Multivariable analysis OR (95\% CI) & Multivariable analysis OR
(95\% CI)\tabularnewline
\midrule
\endhead
& OR & 95\%CI & P value & OR & 95\%CI & P value\tabularnewline
V-Bigeminy & 4.06 & (1.17,14.07) & 0.027 & & &\tabularnewline
PVC burden & 1.35 & (1.14,1.58) & 0.000 & 1.34 & (1.11,1.61) &
0.002\tabularnewline
LVEF & 0.76 & (0.58,1.00) & 0.049 & & &\tabularnewline
\bottomrule
\end{longtable}

PVC, premature ventricular contraction; OR, odds ratio; CI, confidence
interval; LVEF, left ventricular ejection fraction

Figure legends:

Figure 1. The incidence of adverse events in pregnant women with or
without PVC. The incidence of adverse events is higher in PVC cases
(11.65\%) than normal controls without PVC (2.93\%). * indicates
p\textless{}0.05

Figure 2. Incidence of adverse fetal events in low PVC burden (A),
medium PVC burden (B) and high PVC burden group (C). A: low PVC burden
\textless{}the 33rd percentile (\textless{}1.69\%), B: medium PVC
burden, the 33rd percentile - the 67th percentile (1.69\%-4.77\%), C:
high PVC burden \textgreater{}the 67th percentile
(\textgreater{}4.77\%), * indicates p\textless{}0.05\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

