Objectives To determine cardiac and fetal/neonatal event rates among pregnant women with premature ventricular contractions (PVCs) and compare with control groups.
Methods Prospective case–control cohort study: 53 consecutive pregnancies in 49 women referred to the St. Paul’s Hospital between 2010 and 2016 with PVC burden >1% in women without underlying cardiac disease. Maternal cardiac and fetal/neonatal outcomes were compared with two pregnant control groups: (1) supraventricular tachycardia (SVT) group of 53 women referred for a history of SVT/SVT in the current pregnancy and (2) low-risk group of 53 women with no cardiac disease.
Results The maximal PVC burden was 9.2% (range 1.1%–58.7%). Six of 53 (11%) pregnancies were complicated by a maternal cardiac event: heart failure n=1 and sustained ventricular tachycardia requiring therapy n=5 as compared with no cardiac events in both control groups. All women with an adverse event had a PVC burden >5%. Seven (13%) pregnancies were complicated by an adverse fetal and/or neonatal event and this was similar to the normal control group (5 (9%), P=0.45) and significantly less than the SVT group (16 (30%), P=0.03). The adverse fetal event was driven by small for gestational age neonates and preterm delivery.
Conclusions In our cohort of pregnant women with a structurally normal heart and ‘high’ PVC burden, we found an adverse maternal event rate of 11%, and all events were successfully managed with medical therapy. The rate of adverse fetal events in the PVC group was similar to the normal control group.
- premature ventricular beats
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Premature ventricular contractions (PVCs) in individuals with a structurally normal heart are usually considered benign.1 2 However, very frequent PVCs, defined as greater than 10% of all QRS complexes on standard 24-hour Holter monitoring, have been found to be associated with the presence or subsequent development of left ventricular dilatation and dysfunction.3–5 Treatment of frequent PVCs in patients with impaired ventricular function can result in improvement or normalisation of ventricular function.
PVCs are becoming increasingly recognised during pregnancy and it may be that pregnancy unmasks pre-existing PVCs or that they are occurring de novo. PVCs in pregnancy pose an additional challenge, as the maternal and fetal implications are not known in this already cardiac overloaded state. There is minimal data published in this area. Small studies have suggested that the incidence of PVCs decreases during the postpartum period in women with new onset of ventricular arrhythmia during pregnancy.6 7 Beta-blockers such as metoprolol have resulted in a significant decrease in PVC burden during pregnancy.8 The objective of this study was to determine the rate of maternal cardiac and fetal/neonatal adverse events among pregnant women with PVCs and compare with relevant control groups.
Study design and population
This is a prospective case–control study of consecutive pregnancies referred to the St. Paul’s Hospital Cardiac Obstetrics Clinic. The cases were consecutive patients referred for findings of or complaints secondary to PVCs between January 2010 and December 2016. All patients with greater than 1% PVC burden on at least one Holter monitor in pregnancy were eligible. Exclusion criteria were (1) women with palpitations but no documented PVCs, (2) pregnancy that resulted in spontaneous abortion <20 weeks, (3) documented structural cardiac disease and/or (4) history of cardiovascular events. The first control group consisted of the first 53 consecutive age-matched women referred to the same clinic between January 2010 and December 2016 for a history of supraventricular tachycardia (SVT) or SVT in the current pregnancy with a PVC burden of <1% on Holter monitoring. The second control group consisted of women considered to have a low-risk normal pregnancy with no cardiac diagnosis and consisted of the first 53 consecutive age-matched women meeting these criteria in 2016. The inclusion of two control groups allows for two different perspectives with comparison of cardiac and fetal/neonatal outcomes in the PVC group with a normal population and a similarly perceived low-risk arrhythmia population.
Clinical and electrocardiographic data were collected at the time of the initial clinic visit for the PVC and SVT control group. An echocardiogram was also performed in the first trimester in the PVC and SVT control groups. Subsequent clinic visits and investigations were dictated by clinical status. The normal control group was followed as per routine obstetric care. The following data were recorded for the women with PVCs and for both control groups: age, comorbid medical conditions (pulmonary disease, thyroid dysfunction, hypertension, diabetes mellitus), smoking history, New York Heart Association functional class, gestational age, parity, complaints of presyncope/syncope/palpitations,and medications during pregnancy. Family history was obtained, and no women self-reported a family history of any cardiomyopathy or sudden cardiac death. Obstetric risk factors for adverse fetal/neonatal events were also recorded, including (1) prior pregnancy history of premature rupture of membranes, incompetent cervix or caesarean section and (2) antepartum bleeding >12 weeks gestation, febrile illness or uterine/placental abnormalities during current pregnancy and smoking, anticoagulation use, multiple gestation and maternal age <20 and >35 years.
An experienced echocardiographer (JG) interpreted all echocardiograms at the time of study enrolment to ensure that there was no evidence of structural heart disease in the PVC group and to document left ventricular ejection fraction. A standard 12-lead ECG from preconception (when available), antepartum and postpartum period was reviewed and, when possible, PVC morphological patterns were analysed to determine the PVC origin. PVCs with inferior axis and left bundle branch block (LBBB) pattern were determined to most likely originate from the right ventricular outflow tract (RVOT). PVCs with other morphological patterns were broadly labelled as being either from the left or right ventricle. Holters were performed over a 24-hour period and analysed for total number of QRS complexes, total number of PVCs and total runs of non-sustained ventricular tachycardia (NSVT) (ie, run with >3 consecutive PVCs but <30 s). PVC burden was determined from total number of PVCs in total QRS complexes.
All pregnant women with PVCs and the SVT control group were followed from the time of referral until 6 months postpartum. The normal control group was followed for up to 1 week postpartum. Adverse events during the ante-, peri- and postpartum periods were classified as maternal cardiac, fetal/neonatal and obstetric, respectively. Two physicians (JG, CT) blinded to the women’s baseline characteristics independently verified adverse events. Adverse cardiac events were defined as pulmonary oedema (documented by chest radiograph, or by crackles heard over at least one third of posterior lung fields and jugular venous distension), sustained ventricular tachyarrhythmia (>30 s), multiple runs of NSVT (>10 runs in 24 hours), stroke, cardiac arrest or cardiac death. Fetal and neonatal complications were defined as premature birth (<37 weeks gestation), small-for-gestational-age birth weight (<10th percentile for gestational age or <2500 g), respiratory distress syndrome, intraventricular haemorrhage, fetal death (after 20 weeks gestation and before birth) or neonatal death (from birth to age 28 days). Obstetric complications were defined as maternal death from non-cardiac causes, pregnancy-induced hypertension (systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg measured on two separate occasions) or postpartum haemorrhage (blood loss >500 mL after vaginal delivery or >1000 mL after caesarean section, requiring transfusion, or accompanied by a drop in haemoglobin level >20 g/L).
All data were analysed using SPSS V.20.0. Data are presented as median values with IQR or mean±SD. The two-sided unpaired Student’s t-test or Wilcoxon rank-sum test, as appropriate for distribution, was used to compare continuous variables between groups. Fisher’s exact test was used to analyse categorical variables between groups. Logistic regression analysis was used to evaluate factors associated with adverse events. P value of <0.05 was considered statistically significant.
Sixty-seven pregnancies were seen in the Cardiac Obstetrics Clinic for PVC assessment over the study period. Fifty-three pregnancies in 49 women fulfilled our study criteria (table 1). Seven pregnancies were excluded as there was no available Holter monitor data, and seven pregnancies were excluded as the PVC burden was <1%. Maternal age at delivery ranged from 18 to 42 years (median 33 years). One woman had a history of sustained ventricular tachycardia (VT) originating from the RVOT for which she had a cardiac intervention in the form of a VT ablation and she was not on a beta-blocker prepregnancy. There was no reported history of syncope in the PVC group. Other than the arrhythmia diagnosis, the PVC and SVT/normal control groups were similar with respect to comorbidities (table 1).
The underlying rhythm for the entire PVC study cohort was sinus rhythm. PVCs with an LBBB and inferior axis, most likely of RVOT origin, were found in 90% of ECGs that captured PVCs in pregnancy (48 of 53 pregnancies). The mean PVC burden as documented from the baseline Holter was 13.9%±11.3%. The baseline Holter was performed just prior to or at the time of referral (46% performed in the first trimester, 22% performed in the second trimester, and 32% performed in the third trimester). The median maximal documented PVC burden was 9.2% (range 1.1% to 58.7%). Twenty-five pregnancies had a maximal PVC burden >10%, and of these, 17 pregnancies had a PVC burden >20%. Overall, there was a decline in PVC burden into the postpartum period; however, there was great variability between individuals (figure 1). Twenty five of 53 (47%) pregnancies were treated with a beta-blocker (metoprolol n=21, bisoprolol n=3, sotalol n=1). The mean maximal doses were metoprolol 38.7±24 mg twice daily and bisoprolol 3.3±1.4 mg daily. The mean gestational age when beta-blockers were started was 22±13 weeks. Reasons for beta-blockers initiation in pregnancy included symptom control (n=9), physician concern regarding PVC burden (n=10) and secondary to runs of VT (n=6).
Among the PVC cohort, palpitations were reported in 78% and presyncope in 24% of pregnancies. Syncope was experienced in one pregnancy in relation to a run of VT at 16 weeks' gestation. Six of 53 (11%) pregnancies in the PVC cohort were complicated by at least one adverse maternal cardiac event. Heart failure requiring diuretic therapy occurred in one pregnancy, sustained VT requiring therapy occurred in two pregnancies in two women, and multiple runs of NSVT (>10 in 24 hours) occurred in three pregnancies in three women (table 2). Both women with sustained VT were admitted to hospital for therapy. All adverse maternal cardiac events were successfully managed with medical therapy during the pregnancy. No pregnancies were complicated by stroke, cardiac arrest or cardiac death. We did not identify any factors associated with an adverse cardiac event in the PVC group (table 3). However, 100% of women with an adverse cardiac event had a maximal documented PVC burden of >5% as opposed to 70% of women without an event (P=0.05). As defined by the study criteria, there were no adverse maternal cardiac events in the SVT or normal control groups. In the SVT group, 20 (38%) patients had SVT in pregnancy that ranged from a single episode to hospitalisation for medical treatment and/or cardioversion.
With the exception of the one woman who required VT ablation postpartum, PVC burden was <1% by 6 months postpartum in the remaining four women who had experienced sustained VT or multiple episodes of NSVT during pregnancy. Cardiac MRI was performed in all of these women postpartum, and there was no structural heart disease identified.
Obstetric and fetal outcomes
The 53 pregnancies resulted in 53 live births in the PVC group. The most frequently used method of anaesthesia in the PVC group was an epidural in 54% of deliveries and spinal in 15% of deliveries. Sixty-eight per cent (36/53) of the deliveries were vaginal deliveries, and induction was used in 36% of cases. Caesarean deliveries occurred in the remaining 17 pregnancies for the following indications: previous caesarean delivery/planned (n=7), failure to progress (n=2) and fetal distress (n=8). Caesarean delivery was not performed for cardiac indications in any of the women. Adverse obstetric outcomes are shown in table 4.
Seven of 53 (13%) pregnancies were complicated by an adverse fetal and/or neonatal event in the PVC group (table 4). There was a trend towards obstetric risk factors among pregnancies complicated by a fetal/neonatal adverse event (table 5). We found that there was an increasing risk of adverse fetal/neonatal events with increasing obstetric risk: (1) women with low perceived cardiac risk (PVC burden <10% and no cardiac events) and no obstetric risk factors had a rate of 0% (0/9); (2) women with high perceived cardiac risk (PVC burden >10% and/or cardiac event) and no obstetric risk factors had a rate of 10% (2/20); (3) women with low perceived cardiac risk and presence of obstetric risk factors had a rate of 13% (2/15); (4) women with both high perceived cardiac risk and obstetric risk factors had the highest rate at 40% (4/10). The 40% rate suggests that there may be some synergistic negative effect with both cardiac and obstetric risk factors present. No relationship between maternal cardiac events, NSVT or beta-blocker use was found with adverse fetal/neonatal outcomes (table 5).
Rates of adverse fetal/neonatal events were significantly lower in the PVC group at 13% vs 30% in the SVT group. Three women with SVT and an adverse fetal event had recurrent symptomatic episodes of SVT, and the others had a stable course with respect to the SVT diagnosis. There was no difference in the rates of adverse obstetric and fetal/neonatal events between the PVC and normal low-risk pregnancy group.
This is the first study to examine the cardiac and fetal/neonatal outcomes in consecutive pregnant women evaluated for a high burden of PVCs. We have found that among pregnant women with a structurally normal heart and ‘high’ PVC burden, there is an important incidence of cardiac events at 11%, but all were successfully managed with medical therapy during pregnancy. There were no heart failure or VT-related outcomes in either control group. Obstetric and fetal/neonatal outcomes in the PVC group were similar to the low-risk normal pregnancy group. In fact, the SVT control group had a significantly higher number of adverse fetal/neonatal events as compared with the PVC group.
Among a cohort of 110 pregnant women presenting with palpitations and/or presyncope, Shotan et al 7 found that 59% had evidence of PVCs on Holter monitoring. Although this was higher than that observed in an asymptomatic control group, there was no direct association found between the symptomatic episodes and documented arrhythmia on Holter monitoring. Similarly, we did not find an association between symptoms and PVC burden in our cohort of women with a ‘high’ PVC burden. These results support the notion that palpitations during pregnancy are in most cases related to the pregnancy-related changes in heart rate, stroke volume, peripheral vascular resistance and hormones.7–11 Nevertheless, we did find an important incidence of cardiac events in this patient cohort that was driven by hospitalisation for VT requiring treatment. All these women remained stable with these episodes and responded to medical therapy. In fact, in all but one woman, medical therapy was weaned in the postpartum period and recurrent VT was not an issue. The woman who required VT ablation postpartum, had a focus at the aortomitral continuity. Although outcomes are good for this patient population, our results suggest that women with a ‘high’ burden of PVCs should not be overlooked. In fact, it should be considered that the outcomes were likely favourable as these women were medically managed. We found that all women with a cardiac event had a PVC burden >5% as opposed to the inclusion criteria of 1%. The important message from this study is that VT can occur in pregnant women with a high PVC burden, but can be managed conservatively with medication during pregnancy in the majority of cases. Perhaps women with these features should have at least one follow-up with Holter assessment in a Cardiac Clinic specialised in pregnancy and maintain a connection should a cardiac event occur. Aggressive strategies such as ablation or implantable defibrillator should not be pursued until it can be determined that this remains a persistent issue beyond several months postpartum.
PVCs originating from the right ventricle without underlying structural heart disease are thought to be benign.12 A study of 61 patients with no structural heart disease and PVCs originating from the right ventricle demonstrated no occurrence of sudden death, development of sustained VT or any cardiomyopathy.12 In our pregnancy cohort, we found that 92% of PVCs likely originated from the RVOT. This is consistent with the study by Nakagawa et al in which the majority (73%) of their 11 pregnant women had PVCs originating from the RVOT. Outside of pregnancy, increasing PVC burden and duration of PVCs have been found to be detrimental to cardiac function. In a study of 174 patients referred for catheter ablation of symptomatic PVCs, Baman et al found that those with reduced LVEF (<50%) had 33% PVC burden compared with 13% PVC burden in those with normal LVEF (>50%).3 There was a significant improvement in LVEF after successful ablation of PVCs. Duration of PVCs has also been found to be associated with development of reversible cardiomyopathy.13 In our cohort of pregnant patients, all women had a normal left ventricular ejection fraction, and MRI confirmed those with a cardiac event to have a structurally normal heart in the postpartum period. As pregnancy only transiently increases PVC burden, the duration may not be sufficient for cardiomyopathy to develop. In our one pregnant patient who developed heart failure, the PVC burden was 17% and left ventricular ejection fraction was 60%, suggesting that the heart failure occurred likely due to a combination of ventricular ectopy and the already volume overloaded state of pregnancy.
In this cohort of pregnant women with a structurally normal heart and high PVC burden, the rate of adverse fetal/neonatal events was 13% and not significantly different than that of the normal control group at 9%. This was mostly driven by premature delivery and small for gestational age neonates. Previous studies examining pregnant women with other forms of heart disease have reported higher rates of neonatal complications.14–20 Specifically, in a Canadian prospective study of neonatal outcomes in pregnant women with all forms of heart disease, adverse neonatal outcomes occurred in 18% of pregnancies in the heart disease group compared with 7% of healthy pregnant controls.21 In fact, our study would suggest that the SVT group warrants closer attention in pregnancy as there was a significantly higher number of adverse fetal/neonatal events in this group as compared with the PVC group. In our study, there was a trend to increasing adverse fetal/neonatal events among women who had obstetric risk factors. With obstetric risk factors added to the risk profile in women with low perceived cardiac risk, the adverse neonatal event rate went from 0% to 13% with the addition of obstetric risk factors. Similarly, among women with a high perceived cardiac risk, the adverse neonatal rate went from 10% to 40% with the addition of obstetric risk factors. These results should be interpreted with caution due to the small sample size. However, previous work has also shown that obstetric risk factors are strongly associated with adverse neonatal events, and in this patient cohort were highly prevalent at 54%. Beta-blockers are an acceptable treatment for symptomatic control of PVCs in pregnancy.22 Although no teratogenicity has been reported, intrauterine growth restriction, neonatal bradycardia and hypoglycaemia have been associated with propranolol secondary to its beta-2 mediated effect.23 24 Ersbøll et al found that among 175 pregnant women with structural heart disease, beta-blocker therapy was associated with small for gestational age neonates.25 We did not find substantial difference in newborn weight regardless of beta-blocker exposure suggesting that perhaps its fetal impact is minimal in women with a structurally normal heart.
Because all women included in this prospective study were receiving care at a tertiary care cardiac centre, a referral bias may exist. However, it is important to note that at the time of referral, none of the women had suffered a cardiac event. Most of the women referred to the clinic for a high PVC burden were symptomatic. This may lead to a bias as asymptomatic women with a high PVC burden may not be referred and, hence, not included in this study. Because of the small sample size, this study was not powered to identify multiple predictors of outcomes. Larger sample sizes would be needed to identify additional determinants of outcome. Holter monitoring was performed according to the discretion of the clinician and, hence, performed at different time points in each patient. Structural heart disease was ruled out at the time of study enrolment by echocardiography, and among those with a cardiac event cardiac MRI ruled out structural heart disease after delivery. However, there is no longer-term follow-up to determine if structural heart disease developed later and accounted for the PVC burden.
In our cohort of pregnant women with a structurally normal heart and ‘high’ PVC burden, we found overall maternal outcomes to be favourable. Eleven per cent of pregnancies were complicated by a cardiac event, but all were successfully managed with medical therapy during pregnancy. With the exception of one pregnancy, no further therapy was required in the postpartum period and PVC burden was found to decrease. As such, aggressive strategies such as ablation or implantable defibrillator should not be pursued unless there is a persistent issue several months postpartum. The rate of adverse obstetric and fetal/neonatal outcomes in the PVC group was comparable to the normal pregnant population.
What is already known on this subject?
There is minimal knowledge with respect to the impact of premature ventricular contractions (PVCs) in pregnancy on adverse cardiac and fetal/neonatal events.
What might this study add?
This is a prospective case–control study of pregnancies complicated by a high burden of PVCs among women without structural heart disease. We have learnt in this population that there is an adverse cardiac event rate of 11%, and an adverse fetal/neonatal event rate of 13% which is similar to a normal control group (9%) but significantly lower than a supraventricular tachycardia control group (30%). The fetal event rate was driven by small for gestational age neonates and preterm delivery.
How might this impact on clinical practice?
Women found to have >1% PVC burden in pregnancy can be reassured that they will have fetal/neonatal outcomes comparable to the normal pregnant population. However, these women do experience an increased cardiac event rate, warranting consultation and in select cases ongoing follow-up, with a Cardiologist experienced in looking after pregnant women with cardiac disease.
The authors thank Tee Kow for the technical and administrative support.
Contributors CT collected patient data and assisted in manuscript writing. MK identified patients in clinic and provided critical feedback on the manuscript. MD was involved in study design and manuscript review. MO, MQ and AC assisted with data collection. EH and BM identified patients in clinic and recruited them for the study. CS was involved in study design and manuscript review. JG was involved in study design, data review, statistical analysis and manuscript writing.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Ethics approval Obtained from the University of British Columbia Research Ethics Board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No unpublished data available.