Electrocardiographic changes in hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy are a major cause of poor pregnancy outcome and complicate ∼6–11% of all pregnancies.1 These disorders encompasses a spectrum of conditions, which range

in severity from a mild increase in blood pressure (BP) at term with no additional signs/symptoms or adverse sequelae to multisystem conditions with the potential for significant maternal,

fetal and neonatal harm. When diagnosed during pregnancy, hypertension disorders increase the maternal risk of placental abruption, organ failure, cerebrovascular accident and disseminated

intravascular coagulation, as well as fetal risk of intrauterine growth restriction, intrauterine death and prematurity.2 Traditionally, hypertensive disorders during pregnancy are

classified into four categories: (a) chronic hypertension, (b) preeclampsia–eclampsia, (c) preeclampsia superimposed on chronic hypertension and (d) gestational hypertension.1 Nevertheless,

the Society of Obstetricians and Gynecologists of Canada (SOGC) recently released revised guidelines that classified hypertension disorders of pregnancy as pre-existing hypertension,

gestational hypertension (with the options to add ‘with comorbid conditions’ or ‘with evidence of preeclampsia’ to either category), preeclampsia or ‘other hypertensive effects’ (transient

hypertensive effect, white-coat and masked hypertensive effects).3 The latter category was added to raise awareness that office BP that is not consistently elevated may still be associated

with elevated risks compared with consistently normal BP.4 Among the investigations currently used to classify hypertensive disorders of pregnancy (serum creatinine, fasting blood glucose,

serum potassium and urinalysis), interpretation of the ECG is an important component in the evaluation of cardiovascular adaptations during pregnancy and it has been recently suggested as a

potential tool to identify women at increased risk for the development of these conditions.3 NORMAL ADAPTATIONS There is a clear suggestion that pregnancy affects the ECG at some time point

and that there is restoration of these pregnancy-induced changes late in pregnancy or following delivery (Figure 1). Heart rate (HR) increases progressively throughout the pregnancy,

reaching a peak during the third trimester. This increase in HR seems related to hormonal factors in early stages of pregnancy and later to increased left atrial diameter and sympathetic

activation (sinus-node remodelling). Gestational age also impacts QRS complex and T waves, promoting a leftward axis shift as pregnancy progresses. In particular, a leftward deviation of the

mean QRS axis during the second and third trimesters of pregnancy and then rightward before delivery is observed in the majority of women. PR interval exhibits a significant reduction in

the mean values during pregnancy,5 while the QRS amplitude generally increases slightly in the late pregnancy (but without a clear evidence of left ventricular hypertrophy). No clinically

significant changes occur in other ECG intervals (including QT interval) or cardiac rhythm (Figure 1). FEATURES OF INCREASED RISK Only a few studies have investigated the ECG changes during

normal pregnancy and little is known about ECG alterations during pregnancy-induced hypertensive disorders. Although little is known about electrophysiological cardiac alterations in

pregnant women with hypertensive disorders, there is evidence that hypertensive disorders of pregnancy can be associated with changes in P-wave morphology and QT interval. Clinical studies

have produced conflicting results with regard to QT interval changes and its time course during gestation. The rate-corrected QT interval seems to be unaffected by normal pregnancy,5 while

pregnancies with abnormal uterine perfusion that developed pathological outcomes (including pre-eclampsia) showed a trend towards shorter QTc intervals compared with pregnant women with

normal perfusion.6 Interestingly, the QTc interval of women with pathological pregnancy outcomes appeared to shorten progressively throughout the second half of gestation, before the onset

of clinical symptoms of hypertension or proteinuria.6 On the other hand, Isezuo and Ekele7 showed that eclampsia was associated with prolonged ventricular repolarization. Compared to

controls, the eclamptics had higher frequency of sinus tachycardia (9.0% _vs_. 13.3%) and abnormal QTc (46.7% _vs_. 6.6%, odds ratio (OR): 9.2; 95% confidence interval (CI): 1.61–68.48,

_P_=0.01) as measured on the surface ECG.7 For this mixed nature of the evidence, the analysis by Raffaelli _et al._8 published in the current issue of the _Journal_ adds further data, which

need to be combined with the previous literature. Briefly, the authors recruited 76 women affected by pre-eclampsia and a control group of pregnant women without cardiovascular disease or

gestational hypertension. A standard 12-lead ECG was performed on all patients prior to delivery.8 The routine evaluation of the ECGs in both groups was mostly non-pathological. However,

pre-eclamptic women showed a lower HR (77.4±14.3 _vs_. 81.6±11.0 b.p.m.; _P_=0.005), a longer mean QTc interval (442.7±26.7 _vs_. 423.7±20.7 ms; _P_<0.001) and a higher QT dispersion

(24.0 _vs_. 22.0 ms; _P_<0.001) than the control group.8 Notably, QT dispersion is an indicator of inhomogeneity in ventricular activity and its prolongation is correlated with an

increased incidence of ventricular arrhythmias and is a predictor of all-cause mortality.9 Thus, a prolonged QT dispersion could explain the increased incidence of serious ventricular

arrhythmias and adverse outcomes in pregnant women with pre-eclampsia. Nevertheless, assessing the acute cardiac effects of pre-eclampsia on ventricular repolarization, Raffaelli _et al._8

also documented that treatment with MgSO4 was an independent predictor of prolonged QT interval (_P_<0.001). Although intriguing, the lack of a formal interaction test between measures of

ventricular repolarization and MgSO4 administration does not support the hypothesis that alterations in the QT interval precede clinical manifestations of eclampsia (i.e., the prolonged QTc

interval might be only the result of high-dose administration of MgSO4). Thus, the notion that increased ventricular repolarization heterogeneity (as documented by higher values of QT

dispersion) is a spontaneous high-risk feature of pre-eclampsia for the development of adverse events remains questionable. More interestingly, the ancillary analysis by Raffaelli _et al._8

demonstrated that P-wave duration was significantly longer in the pre-eclamptic women than in the control group. This finding is consistent with a previous prospective screening study from

our group, which investigated the potential additive role of standard ECG in the identification of pregnant women at increased risk for hypertensive complications3 (Figure 2). Specifically,

12-lead ECG was recorded at the first antenatal visit and the following ECG parameters were analyzed: HR, QRS duration, QTc interval, Cornell voltage, presence of ST-T abnormalities and left

atrial abnormality in lead V1. The primary outcome of our study was the development of gestational hypertension, pre-eclampsia and eclampsia. The secondary outcome was a composite measure

of hypertensive disorders and other pregnancy complications. In a multivariable model, mean arterial pressure (MAP) and left atrial abnormality were independent predictors of hypertensive

disorders. In particular, the presence of left atrial abnormality in lead V1 was associated with a fourfold increased risk of developing hypertensive disorders during pregnancy (OR: 4.35;

95% CI: 1.84–10.31; _P_=0.001). The same prediction model was also able to identify pregnant women at increased risk for the occurrence of maternal and fetal/neonatal complications (Figure

2). PERSPECTIVES Pregnancy is physiologically associated with changes in HR, cardiac output and intravascular volume. These changes facilitate the adaptation of the cardiovascular system to

the increased metabolic needs of the mother enabling adequate delivery of oxygenated blood to the peripheral tissues and to the fetus.10 These alterations in cardiovascular parameters during

pregnancy suggest the likelihood of an altered ECG during pregnancy. Typically, ECG changes observed during normal pregnancy include sinus tachycardia, left axis deviation, ectopic beats,

inverted or flattened T waves, a Q wave in lead DIII and the augmented voltage unipolar left foot lead5 (Figure 1). The identification of some ECG changes induced by a normal pregnant state

helps to establish a reference for comparison. Nevertheless, for many of the clinical manifestations of hypertensive disorders of pregnancy pathological ECG changes have yet to be clearly

determined. In the last few years, particular attention has been placed on changes of P wave morphology2, 3 (Figure 2) and QT interval6, 7, 8 and their modifications during pregnant state.

However, clinical studies generated mixed evidence and some findings were based on limited clinical observations. Thus, it is still unclear whether ECG variations are useful to predict

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2013; 36: 698–704. Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Cardiology and Cardiovascular Pathophysiology, Hospital ‘S.M. della

Misericordia’, Perugia, Italy Fabio Angeli * Division of Obstetrics and Gynecology, Hospital ‘San Matteo degli Infermi’, Spoleto, Italy Enrica Angeli * Department of Internal Medicine,

Hospital of Assisi, Assisi, Italy Paolo Verdecchia Authors * Fabio Angeli View author publications You can also search for this author inPubMed Google Scholar * Enrica Angeli View author

publications You can also search for this author inPubMed Google Scholar * Paolo Verdecchia View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to Fabio Angeli. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Angeli, F., Angeli, E. & Verdecchia, P. Electrocardiographic

changes in hypertensive disorders of pregnancy. _Hypertens Res_ 37, 973–975 (2014). https://doi.org/10.1038/hr.2014.128 Download citation * Published: 21 August 2014 * Issue Date: November

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