Abstract
Background
Little literature exists regarding the syndrome of inappropriate sinus tachycardia during pregnancy. We aimed to further understand the natural history of inappropriate sinus tachycardia in pregnancy, and to explore maternal and fetal outcomes.
Methods
A retrospective, observational cohort analysis of 19 pregnant women who presented with inappropriate sinus tachycardia.
Results
42% attended the emergency department on more than one occasion with symptoms of inappropriate sinus tachycardia; 32% required hospital admission and 26% required pharmacological therapy. There were no maternal deaths, instances of heart failure or acute coronary syndrome, and no thromboembolic or haemorrhagic complications during pregnancy. Rates of caesarean section were similar to the background rate of our unit (32% and 27%, respectively). Rates of induction were notably elevated (58% vs 25%).
Conclusion
Inappropriate sinus tachycardia in pregnancy is associated with high rates of hospitalization and induction of labour, which may not be mandatory given the clinical findings in this group of women.
Keywords
Introduction
The syndrome of inappropriate sinus tachycardia (IST) is a well-recognized, yet poorly understood condition that affects approximately 1% of the population. 1 It is defined by task force criteria as: (1) a sinus heart rate greater than 100 bpm at rest; (2) a mean 24-h heart rate greater than 90 bpm; (3) not due to primary causes; and (4) associated with distressing symptoms of palpitations. 2 Whilst IST is generally considered benign, the palpitations and possible associated symptoms, such as shortness of breath and exercise intolerance, may be severely debilitating. 1
We have previously reported on the presence of IST during pregnancy, 3 which we believe is a relatively frequent, yet underrecognized, phenomenon. To date, there remains only one other case report in the literature. 4 Given this, we sought to further clarify maternal and fetal outcomes of individuals with the condition through a retrospective observational cohort analysis.
Methods
Between January 2016 and January 2017, 24 women were referred to our maternity cardiology service with symptoms compatible with IST. In five women, it was not possible to complete a full diagnostic work-up prior to delivery to definitively confirm the diagnosis in accordance with task force criteria. 2
All women had a primary cause of sinus tachycardia excluded through intensive investigation (full blood count, CRP, renal function, thyroid function, cardiac troponin, NT pro-BNP, plasma metanephrines and echocardiogram in all. For those in whom there was clinical concern about pulmonary embolus, additional chest radiograph and lung perfusion scan were performed.
All data were collected as part of a locally approved service evaluation project (clinical project ID2506 PRN 8506).
Results
Clinical presentation
The 19 women with a definitive diagnosis of IST in pregnancy all described symptoms of palpitations (on exertion ± at rest) and reduced exercise capacity. At the time of their index presentation, they were aged 17–36 years (mean 28 (±6) years) and were in their first to eighth pregnancy (18 singleton, 1 twin). The history of presenting complaint revealed symptom onset in the index pregnancy between 4 and 36 weeks of gestation (mean 20, median 16 and mode 16 weeks of gestation).
On review of the past medical history, 5 out of the 19 women (26%) described prominent cardiac symptoms and/or had a diagnosed arrhythmia outside of pregnancy (IST in four women and a SVT in one. In those with previous IST, the presenting symptoms were distinct and newly occurring during the index pregnancy; they were not a continuation/exacerbation of pre-existing palpitations. Of those in their second or subsequent pregnancy (n = 8), four women (50%) described symptoms compatible with IST in previous pregnancies.
Cardiac investigations demonstrated sinus rhythm in all individuals with no evidence of pathological arrhythmias (Figure 1). The maximum recorded resting heart rate was 101–148 bpm (mean 124 (±16) bpm) with 24-h mean heart rates of 92–118 bpm (mean 99 (±6) bpm). Typically, there was preserved diurnal heart rate variation with a normal nocturnal dip but with frequent daytime tachycardias (of variable duration).
A selection of sample ECGs from four different individuals in the cohort, taken during symptoms and demonstrating sinus tachycardia.
Maternal outcome
Eight women (42%) attended the emergency department on at least one occasion and in six of the individuals (32%), the symptoms were so disabling that they required admission to hospital. Five women (26%) were treated with pharmacological therapies (beta-blockers in all cases). There were no maternal deaths, instances of heart failure or acute coronary syndrome and no thromboembolic or haemorrhagic complications during pregnancy.
Eighteen women delivered after 37 weeks with one woman presenting in spontaneous preterm labour at 35 weeks and 6 days of gestation. Six women (32%) were delivered by caesarean section (three elective, three emergency). This is not dissimilar from the background rate in our unit or in England (27%). 5 All caesarean sections were performed for standard obstetric indications which were unrelated to the maternal cardiac symptoms.
The induction rate was elevated with 11 women being induced (58%); this compares with a national rate of 27% 5 and a local rate of 25% (for corresponding time period). Six women (32% of total cohort) were induced purely because of symptoms of IST with the other five women (26%) being induced for standard obstetric indications, in line with both national and local rates.
All women in this cohort induced for IST had a vaginal birth. Sixteen women (84%) received anaesthetist interventions; eight epidural analgesia, seven spinal anaesthesia and one a remifentanil patient-controlled analgesia. No woman received general anaesthesia. The rate of anaesthetist intervention seen in this cohort is far greater than that reported for the general population of pregnant women in England (41%). 5
There were no maternal deaths. One women (5.3% of cohort) had a significant postpartum haemorrhage of greater than 1000 ml; this compares to national rate of 15.9%. 5 This was thought to be secondary to an atonic uterus and retained placental tissue following vaginal delivery. There was nothing to suggest that either is attributable to the diagnosis or treatment of IST.
In 17 of the 19 women, their cardiac symptoms resolved within a week of delivery allowing discontinuation of medication where it had been started during pregnancy. There were two individuals whose symptoms persisted at first postnatal clinic review and required new or ongoing pharmacological treatment. In the first case, the woman was given a new prescription for ivabradine (beta-blockers contra-indicated due to a history of asthma); this was, however, stopped at four months postpartum due to resolution of symptoms. In the second case, beta-blockers were re-started as the lady had become pregnant again and was suffering progressive and disabling IST-related symptoms.
Fetal outcome
There was no perinatal mortality. All infants were appropriately grown for gestational age. The APGAR scores at one minute were 9 or 10 in all but 2; 6 in one (twin) and 8 in one (singleton). Five-minute APGAR score was 9 or 10 in all but 1; 7 in one (same baby that had a one-minute score of 6).
Discussion
Main findings
Our data demonstrates IST in pregnancy is associated with high rates of hospitalization and induction of labour due to the distressing nature of symptoms.
Strengths and limitations
The cohort described in this paper has broadly similar characteristics to the background population of our unit. However, we recognize that given the relatively small number of women involved, caution must be taken when considering the significance of outcomes.
The diagnosis of IST by task force criteria 2 does not differentiate by gender or parity and thus can be applied to pregnant females as we have in this cohort. Some might debate the validity of this, believing instead that the normal physiological changes in heart rate that occur during pregnancy would frequently lead to resting and exercise tachycardias. We, however, would disagree.
After conception, the release of the pregnancy-related hormones results in vasodilation and a consequent reduction in total peripheral resistance (TPR). In order to maintain an adequate blood pressure, the reduction in TPR is compensated for by an increase in cardiac output (stroke volume × heart rate). The stroke volume is augmented by increasing cardiac preload (via renal-mediated enhancement of fluid retention). The heart rate increases via baroreceptor-mediated alterations in sympathetic/parasympathetic balance with the heart rate increasing progressively throughout pregnancy by 10–20 bpm (reaching a maximum heart rate during the third trimester).6–8 From 18 weeks of gestation, heart rates of more than 100 bpm (more than 105 bpm from 28 weeks of gestation) occurred in more than 10% of observations taken in healthy pregnancy.9–12 Therefore, we believe that a resting heart rate of greater than 100 bpm in a pregnant woman should, in the absence of an identifiable cause, be considered inappropriate. The use of a mean heart rate greater than 90 bpm as a diagnostic criteria for IST in pregnancy is reasonable based on anecdotal evidence but lacks evidence with no known studies that have published normal values for this parameter in pregnant women.
Interpretation
Is IST in pregnancy a distinct arrhythmia?
The majority of individuals only had cardiac symptoms during pregnancy with an abrupt cessation of those symptoms almost immediately postpartum. Additionally, half the women (presenting in their second or subsequent pregnancy) suffered symptoms compatible with IST in previous pregnancies but not in between those pregnancies. This is suggestive of IST in pregnancy being a distinct arrhythmia.
It is biologically plausible, as IST in pregnancy may reflect an exaggerated cardio-autonomic response to the physiological changes of pregnancy. It is known that during pregnancy, there is an increase in sympathetic tone and a change in baroreceptor reflex sensitivity.13,14 These changes could be exaggerated in individuals who develop IST during pregnancy resulting from variable hormonal fluctuations encountered during their pregnancy similar to those that have been identified during the menstrual cycle of some women. 15 Alternatively, there could be a hormonally mediated increase in sinus node sensitivity to the increased sympathetic tone of pregnancy; most specifically relating to an increased surface expression of HCN channels as has been demonstrated in pregnant mice. 16
How should women with IST during pregnancy be managed?
Empathic care and effective communication form the backbone of management. Regarding specific strategies, there is little evidence specific to IST in pregnancy; however, many of the strategies employed for managing IST in non-pregnant individuals may be utilized.
Lifestyle advise includes maintaining good levels of hydration and regular exercise. 17 These have evidence in the treatment of postural orthostatic tachycardia syndrome and may thus be applicable in women with IST given the number of shared physiological and symptomatic charecteristics.18,19
Pharmacological strategies can be used to reduce sinus rate; however, it should be noted this does not always lead to alleviation of symptoms. Traditionally, β-blockers and calcium channel blockers such as verapamil and diltiazem have been used as first-line therapy. Frequently, however, their use is limited by side effects,20–22 and to this end, ivabradine used either alone or in combination with β-blockers may improve symptoms and decrease heart rate with improved patient tollerence.23–28
Physicians are justifiable cautious when prescribing in pregnancy. Labetolol has traditionally been the β-blocker of choice in pregnancy, and is not known to be harmful when used outside the first trimester of pregnancy. Bisoprolol, labetolol, metoprolol and propranolol have been previously classified by the US Food and Drug Administration (US FDA) as category C (adverse effect demonstrated on the fetus in animal studies with no adequate studies in humans) and they should, therefore, only be given if the potential benefits to the mother justify the potential risk to the fetus. Atenolol was classified as category D use is usually discouraged in pregnancy.
When breast feeding, the BNF states that ‘with systemic use in the mother, infants should be monitored as there is risk of possible toxicity due to beta-blockade. However, the amount of most beta-blockers present in milk is too small to affect infants.’ It should be noted that atenolol, being a water-soluble β-blocker, is present to a greater extent in breast milk and is not included in the American Academy of Pediatrics Committee on Drugs, which advises that breastfeeding is possible if the mother is treated with labetolol, metoprolol and propranolol. 28
The BNF advises against the use of non-dihydropyridine calcium channel blockers during pregnancy but states that the amount of verapamil present in breast milk is too small to be harmful. The US FDA classifies non-dihydropyridine calcium channel blockers as category C (adverse effect demonstrated on the fetus in animal studies with no adequate studies in humans). In practice, verapamil and diltiazem can be used if other treatment options are lacking. The American Academy of Pediatrics Committee on Drugs advise that breastfeeding is possible if the mother is treated with diltiazem or verapamil. 28
The BNF also advises against the use of ivabradine in pregnancy and during breast feeding. Although not explicitly classified, the US FDA states that ivabradine may cause fetal toxicity when administered to a pregnant woman (based on animal studies) and that use is not recommended when breast feeding (no data available about excretion into human milk; excreted into milk in animal models). Despite these cautions, the use of ivabradine has been described in a pregnant woman with IST and a tachycardia-induced cardiomyopathy. 4
Radiofrequency ablation of the sinus node perhaps represents the most extreme option in these women. Whilst it has been utilized for the treatment of IST in non-pregnant individuals, it is not always effective and in the pregnant individual holds the additional risk of fetal irradiation.30–34 Ablation has been described in the treatment of a pregnant women with severe tachyarrhythmias not due to IST. 35
Specific to IST in pregnancy generally results in a resolution of symptoms. A number of studies in other groups have shown induction of labour at term to be safe for both mother and baby,36–38 although it still represents a significant medical intervention that not all mothers will want. In our cohort, all inductions of labour were carried out at term. The increased frequency of epidural anaesthesia use was also closely aligned with the rate of labour induction. Given the benign nature of IST, we emphasize the importance of a conservative strategy where possible.
Conclusions
The women described in this paper had pregnancies blighted by the distressing symptoms of palpitations and exercise intolerance with frequent hospital attendances and a high rate of labour induction within the cohort. For this reason, we believe, that the condition warrants further investigation. IST in pregnancy may represent a distinct arrhythmia, possibly mediated by an exaggerated cardio-autonomic response to the physiological changes of pregnancy. Treatment should be primarily conservative, focusing on empathic care, patient education and lifestyle measures such as regular exercise and maintaining good hydration. Pharmacological therapies should only be considered for frequent and highly intrusive symptoms.
Supplemental Material
sj-pdf-1-obm-10.1177_1753495X21990196 - Supplemental material for Pregnancy-related inappropriate sinus tachycardia: A cohort analysis of maternal and fetal outcomes
Supplemental material, sj-pdf-1-obm-10.1177_1753495X21990196 for Pregnancy-related inappropriate sinus tachycardia: A cohort analysis of maternal and fetal outcomes by Alexander Sharp, Charlotte Patient, Janet Pickett and Mark Belham in Obstetric Medicine
Footnotes
Ethics approval
All data collected as part of a local service evaluation project (clinical project ID2506 PRN 8506).
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Informed consent
Not applicable.
Guarantor
MB is the guarantor of the present work.
Contributorship
AS analysed and interpreted the data, and drafted the manuscript. CP acquired the data, analysed and interpreted the data and revised the manuscript for important intellectual content. JP acquired the data, analysed and interpreted the data and revised the manuscript for important intellectual content. MB conceived the research question, acquired the data, analysed and interpreted the data, drafted the manuscript and supervised AS.
References
Supplementary Material
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