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Year : 2014  |  Volume : 2  |  Issue : 2  |  Page : 43-46

Corrected QT Interval (QTc) Among Pregnant Women During Different Gestational Periods

1 Department of Physiology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences, Sattur, Dharwad, Karnataka, India
2 Department of Physiology, Government Medical College, Miraj, Maharashtra, India

Date of Web Publication17-Jun-2014

Correspondence Address:
Vitthal Khode
Department of Physiology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences, Sattur, Dharwad - 580 009, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2321-449x.134579

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Background: Cardiovascular changes and hence electrocardiographic changes do occur as duration of pregnancy proceeds. There is not much data available on particularly QT interval and corrected QT interval (QTc) in different phases of pregnancy. Pregnancy can precipitate cardiac arrhythmias in later phases in apparently healthy women due to changes in the electric activity of the heart and prolonged QTc is one of the causes. Since prolonged QT interval can precipitate arrhythmias, we thought it is essential to find baseline value for QT interval and QTc in different phases of pregnancy to detect pregnant women at risk. Aims: Our aim of the study was to record QTc in pregnant females during different phases to establish fact that QTc can be correlated with duration of pregnancy. Materials and Methods: Cross-sectional study, 202 pregnant individuals were selected from the antenatal clinic with different phases of pregnancy. All were subjected for electrocardiogram (ECG). QTc was calculated using Bazett's formula and QT intervals were correlated with duration of pregnancy. Results: There was significant gradual increase in QTc with duration of pregnancy. There was significant positive correlation between duration of gestation and QTc (r = 0.277) (P < 0.001). Conclusion: QTc prolongation occurs as pregnancy proceeds.

Keywords: Gestational period, pregnancy, QTc

How to cite this article:
Ruikar K, Khode V, Deokar N. Corrected QT Interval (QTc) Among Pregnant Women During Different Gestational Periods. Heart India 2014;2:43-6

How to cite this URL:
Ruikar K, Khode V, Deokar N. Corrected QT Interval (QTc) Among Pregnant Women During Different Gestational Periods. Heart India [serial online] 2014 [cited 2022 Jan 21];2:43-6. Available from: https://www.heartindia.net/text.asp?2014/2/2/43/134579

  Introduction Top

Women have slower cardiac repolarization than men, which manifests as longer heart rate (HR) corrected QT intervals (QTc) on the electrocardiogram (ECG). [1] This sex difference is seen only after puberty. [2] Women are more prone than men to develop torsades de pointes and ventricular arrhythmias after administration of drugs that prolong cardiac repolarization. [3],[4],[5] These studies suggest a role for sex hormones in the response to drugs that alter cardiac repolarization, and animal studies have demonstrated that sex hormones can affect potassium channel expression, ion currents, cardiac repolarization, and QT response to drugs. [6],[7],[8],[9]

During the pregnancy there is a dynamic change in the structure and electric activity of the heart. Pregnancy can precipitate cardiac arrhythmias in later phase apparently well individuals. Potential factors that can promote arrhythmias in pregnancy include the direct cardiac electrophysiological effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia of pregnancy, and underlying heart disease. Among hormones estrogen has been shown to prolong QT interval and precipitate arrhythmias in pregnancy in animal studies. [8],[9] However, there is paucity in human studies regarding QTc in different phases of pregnancy. Estrogen level in the blood increases as pregnancy proceeds. [10] We hypothesized QT interval increases with duration of pregnancy. We recorded the ECG in pregnant females to examine if the heart rate (HR)-QTc increases progressively as duration of pregnancy increases.

  Materials and methods Top

Selection of subjects

This cross-sectional study was conducted in the Department of Physiology and Medicine in our medical institution. After taking approval of ethical committee, randomly 202 pregnant individuals with different gestational periods between the age group 18-30 years, who were attending antenatal clinic were selected for the study. Sample size was calculated to allow detection of a 30% difference in QTc prolongation between different trimesters and with α of 0.05 and power of 0.8. After taking informed consent, history was noted. Physical examination was done. Vitals were recorded. This was followed by cardiovascular examination in which heart sounds, cardiac murmurs, raised jugular venous pressure (JVP), hepatospleenomegaly, and basal crepitation were looked for any cardiac abnormalities. Particular care was taken to exclude the intrinsic cardiovascular disease. Subjects with pregnancy induced hypertension were excluded from the study.

Recording of ECG and calculation of QTc

ECG was recorded in the morning hours between 9.30 to 11.30 am. Five minutes of rest was given to the patient before recording ECG to allay anxiety. ECG was recorded using CARDIART 108T, J8A 14901 machine, bipolar leads with paper speed 25 mm/s. RR interval was calculated by randomly selecting two consecutive on set of QRS complexes in lead 2. QTc for HR was performed by Bazett's formula. The standard clinical correction was Bazett's formula, named after physiologist Henry Cuthbert Bazett, calculating the HR-QTc interval QTc. Bazett's formula was as follows: QTcB = QT√RR where QTc was the QT interval corrected for HR, and RR is the interval from the onset of one QRS complex to the onset of the next QRS complex, measured in seconds, often derived from the HR as 60/HR (here QT is measured in milliseconds). However, this nonlinear formula overcorrects at high HRs and undercorrects at low HRs.

Statistical analysis

All the data entered and analyzed using Statistical Package of Social Sciences (SPSS) version 16. Data were presented as mean ± standard deviation (SD). Differences in demographic variables in different trimester were analyzed by analysis of variance (ANOVA). Difference between the groups was considered statistically significant at probability value of <0.05. To find out the relation between duration of pregnancy and QTc, Pearson correlation and linear regression was done. To determine the accuracy and respective best cutoff values of QTc for different trimester, the receiver operating characteristic (ROC) curves and their corresponding areas under the curve (AUC) were used. A P-value of <0.05 was considered statistically significant.

  Results Top

Among 202 selected pregnant females 42 included in first trimester, 70 included in second trimester, and 90 were included in third trimester. There was no significant difference in demographic variables among pregnant women [Table 1]. There was no significant difference in HR among pregnant females. There was gradual increased QTc with duration of pregnancy. Statistically significant correlation was observed between duration of pregnancy and QTc. Linear regression analysis revealed there was significant relation between duration of pregnancy and QTc (F = 16.65, P < 0.001) with regression coefficient +0.277 R squared value 0.077 with adjusted R 0.072. The formula was constructed for expected QTc depending on duration of pregnancy was expected QTc = 425.6 (constant QTc) + 0.166 × duration of pregnancy in days [Figure 1]. ROC curve of QTc in second trimester of pregnancy was constructed and the AUC was found to be 0.367 (95% confidence interval (CI) Upper Bound 461, Lower Bound 272) and statistically significant (P = 0.007). Additionally, the AUC of the QTc in third trimester was 0.482 (95% CI Upper Bound 563, Lower Bound 400) and statistically insignificant (P = 0.658). The best cutoff values for QTc in second and third trimester and were 449.2 ms (sensitivity 42.9%; specificity 38.8%) and 453 ms (sensitivity 41.4%; specificity 59.3%), respectively.
Table 1: Comparison of different parameters among first, second, and third trimester

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Figure 1: Scatter plot showing relation between QTc and duration of pregnancy. r = 0.277; r2 = 0.077, Y = 425.6 + 0.166X, Y = Predicted QTc, X = Duration of pregnancy in days

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  Discussion Top

The present study was aimed to determine the possible changes in QT interval and QTc with duration of pregnancy. There was gradual increase in QT interval and QTc with duration of pregnancy. There was significant positive correlation between QTc and duration of pregnancy.

Our study had several limitations. We did not measure estrogen and progesterone levels in controls and pregnant females. We should have correlated hormonal levels with QTc. We did not perform echocardiography to assess the ventricular function of the heart, which could be a confounding factor in assessing QT Interval. We measured QT interval manually using magnifying lens which cannot be as accurate as computerized measurements. We did not measure serum electrolytes like Na + , K, Ca ++ which can affect QT Interval. An additional limitation is that not all medications affecting QTc were included in our methodology.

Various studies have been made to determine the normal limits of the QT interval in normal healthy individuals. These studies have been used as a baseline to determine abnormal prolongation. In as much as it is very important to make an early and correct diagnosis of prolonged QTc syndrome in pregnant women, it is first necessary to determine the normal range in healthy pregnant women. As there is paucity in the data regarding QTc in different phases of pregnancy, this study may give platform for further studies in obtaining baseline values in normal pregnancy in different trimesters. In our study best cutoff values for QTc in second and third trimester and were 449.2 ms (sensitivity 42.9%; specificity 38.8%) and 453 ms (sensitivity 41.4%; specificity 59.3%), respectively.

In the initial description of Bazett's formula for the QTc for HR, Bazett noted that women had a longer QTc interval than men. Although these observations has been reproduced several times, the mechanism of this gender difference in the QT interval is still unclear. [11],[12],[13] In vitro studies have reached varied conclusions, but the weight of evidence does not support an acute physiologic effect of estrogens or androgens on action potential duration. [14],[15] These studies support the concept that acute electrophysiologic effects of estrogen and progesterone are not responsible for the gender difference in QT interval. [16] In contrast, several studies suggest that estrogen and androgens can alter action potential duration during long-term administration, possibly through the induction of changes in ion channel expression or other chronic effects. [17],[18] Therefore, the issue of whether exogenous estrogen or progesterone alters QT interval is still not resolved.

Gradual increase in QTc with duration of pregnancy could be due to various causes which affect electrical activity of heart. Kadish AH et al., suggested that unopposed estrogen in menopausal women mildly prolongs myocardial repolarization and the effect is reversed by progesterone. [19] So there is possibility of estrogen being cause for prolonged QT interval. There was positive correlation between duration of pregnancy to QTc. The regression analysis between QTc and duration of pregnancy revealed statistically significant correlation. But correlation was weak. Probable reason for weak regression coefficient and low R squared values were manual errors while measuring RR interval in lead 2. However, this study may provide platform for further studies in this direction, with increased accuracy in the measurement of QTc and underlying mechanisms.

  References Top

1.Cheng J. Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and human. Fundam Clin Pharmacol 2006;20:1-8.  Back to cited text no. 1
2.Rautaharju PM, Zhou SH, Wong S, Calhoun HP, Berenson GS, Prineas R, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992;8:690-5.  Back to cited text no. 2
3.Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993;270:2590-7.  Back to cited text no. 3
4.Gowda RM, Khan IA, Punukollu G, Vasavada BC, Sacchi TJ, Wilbur SL. Female preponderance in ibutilide-induced torsade de pointes. Int J Cardiol 2004;95:219-22.  Back to cited text no. 4
5.Drici MD, Knollmann BC, Wang WX, Woosley RL. Cardiac actions of erythromycin: Influence of female sex. JAMA 1998;280:1774-6.  Back to cited text no. 5
6.Liu XK, Katchman A, Drici MD, Ebert SN, Ducic I, Morad M, et al. Gender difference in the cycle length-dependent QT and potassium currents in rabbits. J Pharmacol Exp Ther 1998;285:672-9.  Back to cited text no. 6
7.Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and down regulate potassium channel expression in the rabbit heart. Circulation 1996;94:1471-4.  Back to cited text no. 7
8.Waldegger S, Lang U, Herzer T, Suessbrich H, Binder K, Lepple-Wienhues A, et al. Inhibition of minK protein induced K+channels in Xenopus oocytes by estrogens. Naunyn Schmiedebergs Arch Pharmacol 1996;354:698-702.  Back to cited text no. 8
9.Hara M, Danilo P Jr, Rosen MR. Effects of gonadal steroids on ventricular repolarization and on the response to E4031. J Pharmacol Exp Ther 1998;285:1068-72.  Back to cited text no. 9
10.Tulchinsky D, Hobel CJ, Yeager E, Marshall JR. Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. Am J Obstet Gynecol 1972;112:1095-100.  Back to cited text no. 10
11.Robbins J, Nelson JC, Rautaharju PM, Gottdiener JS. The association between the length of the QT interval and mortality in the Cardiovascular Health Study. Am J Med 2003;115:689-94.  Back to cited text no. 11
12.Altunkeser BB, Ozdemir K, Içli A, Celik C, Akyürek C, Gök H. Effects of long-term hormone replacement therapy on QT and corrected QT dispersion during resting and peak exercise electrocardiography in post-menopausal women. Jpn Heart J 2002;43:1-7.  Back to cited text no. 12
13.Larsen JA, Kadish AH. Effect of gender on cardiac arrhythmias. J Cardiovasc Electrophysiol 1998;9:655-64.  Back to cited text no. 13
14.Prinzmetal M, Ishikawa K, Nakashima M, Oishi H, Ozkan E, Wakayama J, et al. Estrogen and the heart. Am J Obstet Gyencol 1967;98:575-6.  Back to cited text no. 14
15.Gimeno AL, Gimeno MF, Webb JL. Action of sex steroids on the electrical and mechanical properties of rat atrium. Am J Physiol 1963;205:198-200.  Back to cited text no. 15
16.Burke JH, Ehlert FA, Kruse JT, Parker MA, Goldberger JJ, Kadish AH. Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults. Am J Cardiol 1997;79:178-81.  Back to cited text no. 16
17.Pham TV, Sosunov EA, Anyukhovsky EP, Danilo P Jr, Rosen MR. Testosterone diminishes the proarrhythmic effects of dofetilide in normal female rabbits. Circulation 2002;106:2132-6.  Back to cited text no. 17
18.Shuba YM, Degtiar VE, Osipenko VN, Naidenov VG, Woosley RL. Testosterone mediated modulation of HERG blockade by polyarrhythmic agents. Biochem Pharmacol 2001;62:41-9.  Back to cited text no. 18
19.Kadish AH, Greenland P, Limacher MC, Frishman WH, Daugherty SA, Schwartz JB. Estrogen and progestin use and the QT interval in postmenopausal women. Ann Noninvasive Electrocardiol 2004;9:366-74.  Back to cited text no. 19


  [Figure 1]

  [Table 1]

This article has been cited by
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