Pregnancy in women with congenital heart disease ... · Cardiac adaption during pregnancy 41 3...

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Pregnancy in women with congenital heart diseaseKampman, Marlies Aleida Maria

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Citation for published version (APA):Kampman, M. A. M. (2016). Pregnancy in women with congenital heart disease: complications andmechanisms. [Groningen]: Rijksuniversiteit Groningen.

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Chapter 3Cardiac adaption during pregnancy: comparison between women with congenital heart disease and healthy women.

Marlies A.M. KampmanMattia A. E. ValenteJoost P. van MelleAli BalciJolien W. Roos-HesselinkBarbara J.M. MulderArie P.J. van DijkMartijn A. OudijkMonique R.M. JongbloedDirk J. van VeldhuisenPetronella G. Pieper

on behalf of the ZAHARA II investigators

Submitted.

40 Chapter 3

AbsTrACT

background

Pregnancy in women with congenital heart disease (CHD) is associated with cardiovascular

complications and with deterioration in cardiac function. Still data on longitudinal changes

during pregnancy are scarce. Data on right ventricular function parameters are not yet

reported. We aimed to describe serial changes in cardiac dimension and cardiac function dur-

ing pregnancy in women with CHD and compare these to changes seen in healthy women.

We focus on both left and right ventricular parameters.

Methods

We performed a prospective multicenter cohort study. Follow-up with clinical evaluation and

standardized echocardiography at 20 and 32 weeks gestation and one year postpartum was

performed. In women with CHD, pre-pregnancy echocardiograms were also evaluated.

results

We studied 125 women with CHD and 49 healthy women. The absolute level of ventricular

function parameters and diameters differs clearly between women with CHD and healthy

women. No changes occurred in right and left ventricular function parameters and ven-

tricular dimensions during pregnancy in the total population of women with CHD. However,

women with right-sided CHD had a different profile of TAPSE over time compared to healthy

women (p=0.043). Women with left-sided CHD had a different profile of LVEDD over time

compared to healthy women (p=0.045).

Conclusion

Absolute levels of ventricular function parameters and diameters differ between women

with CHD and healthy women. The different patterns over time seen for TAPSE and LVEDD

in women with right-sided and left-sided CHD respectively, compared to healthy women

indicate the importance of echocardiographic follow-up during pregnancy in women with

CHD.

Key words: congenital heart disease, pregnancy, cardiac function, echocardiography.

Cardiac adaption during pregnancy 41

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inTroduCTion

Pregnancy in women with congenital heart disease (CHD) is associated with increased in-

cidences of cardiovascular, obstetric and neonatal complications 1-5. Cardiac complications,

such as arrhythmia and heart failure, are thought to be due to the hemodynamic changes

of pregnancy. Depending on the specific underlying congenital defect, pregnancy can be

associated with persisting structural cardiac remodeling and deterioration in function, such

as dilatation of the subpulmonary ventricle after pregnancy, deterioration of valvular dys-

function and worsening ventricular function 6-10. However, the observations in most of these

studies were not based on longitudinal data. The majority of data on cardiovascular changes

over time during pregnancy is based on studies in healthy women and only a few reports

describe longitudinal cardiovascular changes in women with heart disease 11,12. Most of the

available research focuses on left ventricular parameters 13. Data examining longitudinal

changes in right ventricular function and dimension are scarce in healthy pregnant women

and have never been reported in pregnant women with congenital heart disease 14,15.

Therefore, we aimed to describe serial measurements in cardiac dimensions and systolic and

diastolic function of the right and left ventricle during pregnancy in women with congenital

heart disease. In addition, we compared the serial measurements in women with congenital

heart disease to the changes seen in healthy pregnant women.

MeThods

study population

The ZAHARA II study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy in CHD)

is a national, prospective multicenter cohort study. All consecutive pregnant women with

structural CHD, aged ≥ 18 years, pregnancy duration < 20 weeks and presenting in one

of the eight participating centers were eligible for enrollment. Healthy pregnant women

(nonsmokers, no medication use, aged ≥ 18 years) were recruited from low risk midwife

practices in Groningen and Rotterdam, the Netherlands. The study design and primary results

have been published previously 16,17.

Only women from the ZAHARA II study with singleton pregnancies and complete echo-

cardiographic follow-up (preconception (only applicable for women with CHD), 20 and 32

weeks gestation, one year post-partum) were included for the current study and only the first

pregnancy during the study period was taken into account. Women with a systemic right

ventricle or Fontan physiology were excluded, since various echocardiographic measure-

ments are not validated for these types of congenital heart disease.

42 Chapter 3

The Research Ethics Committee of all participating centers approved the study protocol and

all participating women gave written informed consent. The ZAHARA II study was supported

by a grant from the Netherlands Heart foundation (2007B75).

baseline characteristics and echocardiography

Baseline characteristics were collected using medical records during the first ante-partum

visit and included maternal age, underlying congenital heart disease, previous interventions,

prior cardiac events, cardiac medication use, New York Heart Association (NYHA) functional

class, echocardiography data, co-morbid conditions and obstetric history.

Patients and healthy pregnant women visited the outpatient clinic at 20 and 32 weeks gesta-

tion and one year post-partum for clinical evaluation (including NYHA class assessment) and

standardized echocardiography. All echocardiograms were evaluated offline by four experi-

enced cardiologists at the University Medical Center Groningen, Groningen, the Netherlands.

Transthoracic echocardiographic evaluation was performed according to current guidelines

and recommendations, and adapted to the structural defect when necessary 18-21.

Left ventricular end-diastolic and end-systolic diameters (LVEDD, LVESD), as well as the left

ventricular outflow tract (LVOT) diameter, were assessed on the parasternal long axis view

(PLAX). Left ventricular outflow tract velocity time integral was derived from the apical

five chamber view. Cardiac output was calculated by multiplying LVOT area with the LVOT

velocity time integral and heart rate. Left ventricular ejection fraction was determined using

Simpson’s biplane method using the apical four chamber view and the apical two chamber

view where possible, otherwise Simpson’s monoplane or the eyeballing method were used.

Diastolic function was assessed by pulsed wave Doppler of the mitral inflow (E, A, E/A ratio)

and color tissue Doppler of the septal and lateral mitral annulus (E/E’).

Right ventricular function was measured using the Tricuspid Annular Plane Systolic Excursion

(TAPSE) in the apical four chamber view and the peak systolic color tissue velocity Doppler

of the right ventricular lateral wall assessed at the tricuspid annulus (S’ RV). Maximal right

ventricular end-diastolic diameter was measured using the modified apical four chamber

view. Left ventricular systolic dysfunction was defined as an ejection fraction < 45%. Right

ventricular systolic dysfunction was defined as TAPSE < 16 mm.

statistical analysis

Continuous variables are presented as mean with standard deviation (SD) or medians with

interquartile ranges as appropriate. Absolute numbers and percentages are displayed for

categorical data.

To investigate changes in the serial echocardiographic parameters over time in pregnant

women with CHD and to compare the serial changes over time with healthy pregnant

women, random slope, random intercept linear mixed-effects models were used, adjusted

for age, race and parity. These hierarchical regression models include fixed and random


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(subject-specific) effects, allowing for within subject correlation between repeated measure-

ments. As the evolution of parameters during pregnancy might not be linear, patterns were

investigated graphically, and polynomial transformations were considered where appropri-

ate. Best fit transformations were selected via combined assessment of Akaike’s Information

Criterium (AIC, lower is better) for fixed effects and likelihood ratio tests of nested models

for random effects. Second degree polynomial transformations for changes over time were

selected for the final models. Interaction terms for group membership (pregnant women

with CHD vs. healthy pregnant women; pregnant women with right-sided CHD vs. healthy

pregnant women; pregnant women with left-sided CHD vs. healthy pregnant women) were

introduced as a fixed effect to check for differences in course over time. Women with Tetral-

ogy of Fallot, atrial septal defects, partial atrioventricular septal defects, pulmonary atresia

with intact ventricular septum, Ebstein’s anomaly, abnormal pulmonary venous return, sinus

venosus defects and pulmonary valve stenosis were classified as having right-sided CHD.

Women with ventricular septal defects, aortic valve abnormalities, aortic coarctation, Marfan

syndrome and with a cleft mitral valve were considered to have left-sided CHD.

All statistical analyses were performed using STATA software package (version 11, college

station, Texas, USA) and R: A language and environment for statistical computing (version

3.1.0, R Foundation for statistical computing, Vienna, Austria). A two-tailed p-value < 0.05

was considered significant.

resulTs

During the study period, 213 women with congenital heart disease and 70 healthy women

were included. Eighty-eight pregnancies in women with CHD were excluded because of

a twin pregnancy (n=4), Fontan physiology or a systemic right ventricle (n=15), second

pregnancy in the study period (n=9) or incomplete echocardiographic data (n=60), rendering

125 patients available for analysis. In one healthy woman a previously unknown atrial septal

defect type II was found and 20 women did not have complete echocardiographic follow-up,

resulting in 49 healthy pregnant women included in this analysis.

Baseline characteristics and underlying congenital defects are displayed in table 1. Mean age

was comparable between women with CHD (29.4 ± 4.5 years) and healthy women (30.1 ±

4.1 years; p=0.31) . The majority of patients and healthy controls was nulliparous (62.4% vs.

61.2%, p=0.89) and most of them were in NYHA functional class I (75.2% vs. 98.0%, p<

0.001). Left ventricular systolic dysfunction was seen in 4 (3.2%) women with CHD and 15

(12.0%) had right ventricular systolic dysfunction.

Serial means over time of the ventricular function parameters and the ventricular dimensions

of right and left ventricle are reported in table 2 and displayed in figure 1 and 2. No statisti-

44 Chapter 3

Table 1. Maternal baseline characteristics (prior to pregnancy).

Patients (N=125)N (%)

Healthy women (N=49)N (%)

Demographics and clinical data

Maternal age at conception (years ± SD) 29.4 ± 4.5 30.1 ± 4.1

Parity status

0 78 (62.4) 30 (61.2)

≥ 1 47 (37.6) 19 (38.8)

NYHA class

I 94 (75.2) 48 (98.0)

II 30 (24.0) 1 (2.0)

III 1 (0.8)

Modified WHO class*

I 15 (12.0)

II 81 (63.7)

III 27 (21.6)

IV 2 (1.6)

Mechanical valve prosthesis 10 (8.0)

Arrhythmia 10 (8.0)

Pacemaker 2 (1.6)

Congestive heart failure 4 (3.2)

Hypertension 10 (8.0)

Type of congenital lesion

Abnormal pulmonary venous return 1 (0.8)

Aortic valve stenosis / Bicuspid aortic valve 23 (18.4)

Atrial septum defect 14 (11.2)

Atrioventricular septal defect 7 (5.6)

Ebstein’s anomaly 1 (0.8)

Loeyz-Dietz syndrome 1 (0.8)

Marfan syndrome 7 (5.6)

Other* 1 (0.8)

Other complex cyanotic heart disease † 2 (1.6)

Pulmonary valve stenosis 10 (8.0)

Surgically repaired Aortic coarctation 19 (15.2)

Tetralogy of Fallot after repair 28 (22.4)

Transposition of great arteries with arterial switch 2 (1.6)

Ventricular septal defect 9 (7.2)

Echocardiographic parameters

Left ventricular systolic dysfunction (LVEF < 45%) 4 (3.2)

Right ventricular systolic dysfunction (TAPSE < 16 mm) 15 (12.0%)

*Patient with cleft mitral valve. † 1 patient with a corrected truncus arteriosus, type A; 1 patient with pulmo-nary atresia, atrial septal defect and intact intraventricular septum.


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Table 2. Longitudinal echocardiographic parameters in pregnant women with congenital heart disease and healthy women (mean ± SD).

Pre-pregnancy 20 weeks 32 weeks

1-yr post-partum

Right ventricular parameters

Entire CHD population

Tricuspid annular plane systolic excursion (TAPSE (mm)) 21.2 ± 5.6 22.5 ± 6.1 21.5 ± 6.4 21.0 ± 5.5

Systolic tissue velocity of the lateral wall (S’ RV (cm/s)) 8.4 ± 2.9 9.7 ± 2.9 9.5 ± 3.1 8.7 ± 2.9

Right ventricular end-diastolic diameter (RVEDD (mm)) 38.2 ± 8.3 38.6 ± 7.4 39.1 ± 7.4 37.2 ± 8.0

Women with right-sided CHD




Women with left-sided CHD




Healthy women

Tricuspid annular plane systolic excursion (TAPSE (mm)) -- 26.6 ± 3.5 25.1 ± 4.0 23.9 ± 3.1

Systolic tissue velocity of the lateral wall (S’ RV (cm/s)) -- 11.5 ± 1.3 11.5 ± 1.8 10.6 ± 2.3

Right ventricular end-diastolic diameter (RVEDD (mm)) -- 35.8 ± 4.2 35.5 ± 4.2 35.8 ± 5.0

Left ventricular parameters

Entire CHD population

Left ventricular ejection fraction (LVEF (%)) 57.6 ± 8.0 57.6 ± 8.0 56.9 ± 8.0 55.8 ± 9.3

Mean systolic tissue velocity of the septal and lateral wall (S’ LV (cm/s)) 6.2 ± 1.4 6.9 ± 1.8 7.0 ± 1.8 6.4 ± 1.7

Left ventricular end-systolic diameter (LVESD (mm)) 29.8 ± 5.6 30.9 ± 5.4 30.7 ± 5.3 30.9 ± 5.5

Left ventricular end-diastolic diameter (LVEDD (mm)) 46.3 ± 6.5 46.5 ± 6.9 48.0 ± 6.1 46.8 ± 5.7

Women with right-sided CHD

Left ventricular ejection fraction (LVEF (%)) 56.1 ±7.9 58.1 ± 8.8 56.3 ± 8.1 53.9 ± 9.4

Mean systolic tissue velocity of the septal and lateral wall (S’ LV (cm/s))

6.3 ± 1.2 7.0 ± 1.9 7.1 ± 1.9 6.2 ± 1.7


46 Chapter 3

Table 2. Longitudinal echocardiographic parameters in pregnant women with congenital heart disease and healthy women (mean ± SD). (continued)

Pre-pregnancy 20 weeks 32 weeks

1-yr post-partum


Women with left-sided CHD

Left ventricular ejection fraction (LVEF (%)) 58.8 ± 8.1 57.5 ± 7.3 57.5 ± 7.9 57.9 ± 9.2


6.1 ± 1.6 6.8 ± 1.6 6.9 ± 1.7 6.7 ± 1.7



Healthy women

Left ventricular ejection fraction (LVEF (%)) -- 62.3 ± 5.9 59.4 ± 6.1 60.0 ± 5.6


-- 7.6 ± 1.5 7.7 ± 1.4 7.3 ± 1.1

Left ventricular end-systolic diameter (LVESD (mm)) -- 31.1 ± 4.0 31.6 ± 2.9 30.8 ± 4.0

Left ventricular end-diastolic diameter (LVEDD (mm)) -- 48.1 ± 3.8 47.9 ± 3.5 47.2 ± 3.2

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Figure 1: Serial changes (means with 95% confidence interval) in right ventricular function parameters for the entire population of women with CHD (A, Tricuspid Annular Plane Systolic Excursion (TAPSE (mm)(n=121)); B, Systolic tissue velocity of the right ventricle lateral wall (S’ RV (cm/s)(n=96)) and right ventricular end diastolic diameter (RVEDD (mm)(n=113)) (C).


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cally significant changes occurred during pregnancy in either of the parameters assessed in

the entire population of women with CHD.

Figure 3 compares the fitted longitudinal profiles over time of the right ventricular function

parameters and right ventricular dimension. Women with CHD have lower values of right

ventricular function parameters (TAPSE and systolic tissue velocity of the right ventricle)

compared to healthy women. Right ventricular end-diastolic diameter was larger throughout

pregnancy compared to healthy women. The changes observed in the entire cohort of

women with CHD were comparable to the changes seen in healthy women; no statistically

significant differences were found in the slope of any of the longitudinal profiles, indicating

similar patterns of change over time for both populations.

In women with solely right-sided CHD, the fitted longitudinal profile of TAPSE over time

was significantly different from that in healthy women (p=0.043), with TAPSE remaining

unchanged in women with right-sided CHD (table 2).

The fitted longitudinal profiles over time of the left ventricular function parameters and left

ventricular dimensions are shown in figure 4. Women with CHD have a worse left ventricular

systolic function during pregnancy compared to healthy pregnant women, as displayed by

lower LVEF and systolic tissue velocity. Left ventricular dimensions are comparable between

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Figure 2: Serial changes (means with 95% confidence interval) in left ventricular function parameters for the entire population of women with CHD (A, Left ventricular ejection fraction (LVEF (%)(n=124)); B, Mean systolic tissue velocity of the septal and left ventricular lateral wall (S’ LV (cm/s)(n=91)) and left ventricular end diastolic (C (n=125)) and end systolic (D (n=125)) diameter (mm) for women with CHD.

48 Chapter 3

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Figuren mixed models (2).pzf:RV parameters - Tue Jan 05 13:33:25 2016

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Figure 3: Fitted longitudinal profiles of right ventricular function parameters for women with CHD ( ), and healthy women (

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). (A, Tricuspid Annular Plane Systolic Excursion (TAPSE (mm) (n=116 vs. 47)); B, Systolic tissue velocity of the right ventricle lateral wall (S’ RV (cm/s) (n=91 vs. 39)) and right ventricular end diastolic diameter (RVEDD (mm) (n=105 vs. 41)) (C) Error bars represent 95% confidence interval.

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Figure 4: Fitted longitudinal profiles of left ventricular function parameters for women with CHD ( ) and healthy women (

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). (A, Left ventricular ejection fraction (LVEF (%) (n=116 vs. 49)); B, Mean systolic tissue ve-locity of the septal and left ventricular lateral wall (S’ LV (cm/s)(n=87 vs. 44)) and left ventricular end diastolic (C (n=118 vs 49)) and end systolic (D (n=118 vs 49)) diameter (mm) Error bars represent 95% confidence interval.


3

both groups. We found no statistically significant differences in the slope of the longitudinal

profiles between women with CHD and healthy controls, indicating similar patterns of

change over time for both populations.

The fitted longitudinal profile of LVEDD in women with left-sided CHD over time was signifi-

cantly different from that in healthy women (p=0.045) with LVEDD tending to increase over

time in women with left-sided CHD (table 2).

disCussion

This is the first study that compares the serial changes in ventricular function parameters

and ventricular dimensions during pregnancy in women with CHD to healthy pregnant

women. In addition, this is the first study that describes the serial changes in right ventricular

parameters seen during and after pregnancy in women with CHD. For the serial changes in

the heterogeneous population of women with CHD, we did not find any statistical significant

effect of time and the serial changes in echocardiographic parameters during pregnancy in

women with CHD were comparable to healthy pregnant women, indicating similar patterns

in both populations. However, the absolute levels of ventricular function and dimensions

did clearly differ between women with CHD compared to healthy women. For women with

right-sided CHD fitted profiles of TAPSE over time differed from the pattern seen in healthy

women. Women with left-sided CHD had a different profile of LVEDD over time compared

to healthy pregnant women.

Comparison of our results to other studies is difficult since data on cardiac adaption during

pregnancy in women with CHD or heart disease in general are very rare. Cornette et al.

described a time effect during pregnancy towards a larger LVESD, lower fractional shortening

and lower left ventricular ejection fraction 12. In addition, they found a parabolic effect for

E/E’, stroke volume and cardiac output. In our study, visual patterns and model fit criteria

suggest non-linear variation in parameters over time, however there was no statistically

significant effect of time for any of these parameters. The heterogeneity of the population is

most probably due to this observation, since differences might cancel out when women with

right-sided and left-sided defects are considered together in one population. The fact that

we did find differences in fitted profiles of TAPSE over time in women with right-sided CHD

and of LVEDD over time in women with left-sided CDH compared to healthy controls also

strengthens this argument. Our results on Doppler peak systolic velocity of the left ventricle

were comparable to those described by Bamfo et al. in healthy pregnant women 22. Their

results support our finding that the pattern of longitudinal changes does not differ essentially

from healthy women.

Compared to healthy women, women with CHD in our cohort show lower fitted values for

left ventricular ejection fraction (figure 4). Vasapollo et al. described significant lower LVEF in

50 Chapter 3

healthy women with fetal growth restriction compared to healthy women with uncomplicated

pregnancy outcome 23. The pattern we observe in our study is comparable, with lower LVEF

during pregnancy in women with CHD compared to healthy women. Although we did not

find any deterioration in systolic function during pregnancy, this finding suggests that there

might be an impaired potential in women with CHD to provide the required cardiac adap-

tions necessary to meet the increased metabolic demands of pregnancy. This may contribute

to the higher obstetric and offspring complication rate in women with CHD, since cardiac

dysfunction is related to impaired uteroplacental circulation and offspring complications 17.

The observed difference in fitted values for LVEDD over time in women with left-sided CHD

compared to healthy women may suggest that the volume load of pregnancy is not well

tolerated in patients with these type of lesions; however, lesion-specific data are warranted.

Data on right ventricular function and dimensions during pregnancy are extremely scarce

and have never been described in a longitudinal manner for women with CHD. Vogt and

colleagues were the first to report on systolic tissue velocities of the right ventricle (S’) during

pregnancy in healthy women and did not find a significant change in systolic velocity com-

paring the first with the third trimester 14. Ducas et al. described, in a study using magnetic

resonance imaging (MRI), no change in TAPSE and systolic myocardial velocity of the right

ventricle lateral wall in healthy pregnant women during the third trimester compared to post-

partum values (which were used as baseline measurement) 15. Our results on right ventricular

systolic function in women with CHD are comparable to these findings, but the absolute

values in our patients are considerably lower compared to the healthy women. TAPSE is

related to impaired uteroplacental circulation and offspring complications 17. It might be that

the absolute level of right ventricular systolic function is not sufficient to meet the increased

demands of pregnancy, leading to adverse obstetric and offspring outcome. The observation

that the evolution of TAPSE in women with right-sided CHD is significantly different from

the pattern seen in healthy women, may also point into that direction. It might be that

this subgroup has insufficient capacity to increase TAPSE, in order to accommodate cardiac

output, which may contribute to the increased incidence rates of obstetric and offspring

complications.

It is known for specific congenital lesions, i.e. systemic right ventricles and Tetralogy of Fallot,

that pregnancy can be associated with persistent deterioration in cardiac function 6,8 and

women with cardiovascular complications during pregnancy are at risk for persistent dilata-

tion of the right ventricle 10. Close follow up of high risk patients is still warranted, since small

changes in cardiac function in the individual patient might be clinical relevant, although we

did not find any statistical significant changes in our study cohort.


3

sTrengThs & liMiTATions

This is the first study that assessed the serial changes in ventricular function and dimensions

during pregnancy in women with congenital heart disease and compared these to changes

in healthy pregnant women. The comparison with healthy pregnant women is unique and

makes the results more valuable.

Due to the study design echocardiographic data before pregnancy from patients were

collected retrospectively and in healthy women preconception echocardiography was not

preformed. This hampered the comparison of the serial changes in women with CHD and

healthy controls, since preconception data were not included in this analysis. Several high-

risk congenital lesions (Fontan physiology and systemic right ventricles) were excluded from

analysis. These are the most vulnerable patient groups during pregnancy for cardiac com-

plications and deterioration in cardiac function during and after pregnancy. Excluding these

types of patients may underestimate the effects of pregnancy on maternal cardiac function.

In our study, the visual patterns and model fit criteria suggest non-linear variation in param-

eter values over time, however there was no statistically significant effect of time found for

any of the parameters. This is most probably due to the heterogeneity of the study cohort.

With subgroups analyses for right and left-sided CHD we attempted to compensate for that;

however, insufficient power hampers analyses. Additional, lesion specific research is clearly

warranted.

ConClusion

In this study, we showed that absolute levels of ventricular function parameters and ven-

tricular dimensions differ between women with CHD and healthy controls. The patterns of

change over time seen during pregnancy are comparable between women with CHD and

healthy pregnant women. However, fitted profiles of TAPSE over time in women with solely

right-sided CHD differed significantly from healthy women. In women with left-sided CHD,

fitted profiles of LVEDD over time were significantly different compared to healthy controls.

These findings indicate that serial follow-up of cardiac function and dimensions during preg-

nancy in women with CHD is an important part of the management of pregnancy in women

with congenital heart disease.

ACKnowledgeMenTs

The authors thank dr. J.P.M. Hamer for his contribution in evaluating the echocardiograms.

52 Chapter 3

referenCes

1. Drenthen W, Boersma E, Balci A, et al. Predictors of pregnancy complications in women with

congenital heart disease. Eur Heart J 2010; 31: 2124-32.

2. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with con-

genital heart disease: A literature review. J Am Coll Cardiol 2007; 49: 2303-11.

3. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in

women with heart disease. Circulation 2001; 104: 515-21.

4. Siu SC, Colman JM, Sorensen S, et al. Adverse neonatal and cardiac outcomes are more common

in pregnant women with cardiac disease. Circulation 2002; 105: 2179-84.

5. Roos-Hesselink JW, Ruys TP, Stein JI, et al. Outcome of pregnancy in patients with structural or

ischaemic heart disease: Results of a registry of the european society of cardiology. Eur Heart J

2013; 34: 657-65.

6. Uebing A, Arvanitis P, Li W, et al. Effect of pregnancy on clinical status and ventricular function in

women with heart disease. Int J Cardiol 2010; 139: 50-9.

7. Kamiya CA, Iwamiya T, Neki R, et al. Outcome of pregnancy and effects on the right heart in

women with repaired tetralogy of fallot. Circ J 2012; 76: 957-63.

8. Bowater SE, Selman TJ, Hudsmith LE, et al. Long-term outcome following pregnancy in women

with a systemic right ventricle: Is the deterioration due to pregnancy or a consequence of time?

Congenit Heart Dis 2013; 8: 302-7.

9. Guedes A, Mercier LA, Leduc L, et al. Impact of pregnancy on the systemic right ventricle after a

mustard operation for transposition of the great arteries. J Am Coll Cardiol 2004; 44: 433-7.

10. Kampman MA, Balci A, Groen H, et al. Cardiac function and cardiac events 1-year postpartum in

women with congenital heart disease. Am Heart J 2015; 169: 298-304.

11. Lesniak-Sobelga A, Tracz W, KostKiewicz M, et al. Clinical and echocardiographic assessment of

pregnant women with valvular heart diseases--maternal and fetal outcome. Int J Cardiol 2004;

94: 15-23.

12. Cornette J, Ruys TP, Rossi A, et al. Hemodynamic adaptation to pregnancy in women with struc-

tural heart disease. Int J Cardiol 2013; 168: 825-31.

13. Demirkol S, Balta S, Cakar M, et al. Do we just assess the left ventricle in pregnant women with

structural heart disease? Int J Cardiol 2013; 168: 591.

14. Vogt M, Muller J, Kuhn A, et al. Cardiac adaptation of the maternal heart during pregnancy: A

color-coded tissue doppler imaging study - feasibility, reproducibility and course during preg-

nancy. Ultraschall Med 2014; .

15. Ducas RA, Elliott JE, Melnyk SF, et al. Cardiovascular magnetic resonance in pregnancy: Insights

from the cardiac hemodynamic imaging and remodeling in pregnancy (CHIRP) study. J Cardiovasc

Magn Reson 2014; 16: 1,429X-16-1.

16. Balci A, Sollie KM, Mulder BJ, et al. Associations between cardiovascular parameters and

uteroplacental doppler (blood) flow patterns during pregnancy in women with congenital heart

disease: Rationale and design of the zwangerschap bij aangeboren hartafwijking (ZAHARA) II

study. Am Heart J 2011; 161: 269,275.e1.

17. Pieper PG, Balci A, Aarnoudse JG, et al. Uteroplacental blood flow, cardiac function, and preg-

nancy outcome in women with congenital heart disease. Circulation 2013; 128: 2478-87.

18. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/

ASE recommendations for clinical practice. J Am Soc Echocardiogr 2009; 22: 1,23; quiz 101-2.


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19. Easterling TR, Carlson KL, Schmucker BC, et al. Measurement of cardiac output in pregnancy by

doppler technique. Am J Perinatol 1990; 7: 220-2.

20. Robson SC, Hunter S, Boys RJ, et al. Serial study of factors influencing changes in cardiac output

during human pregnancy. Am J Physiol 1989; 256: H1060-5.

21. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right

heart in adults: A report from the american society of echocardiography endorsed by the euro-

pean association of echocardiography, a registered branch of the european society of cardiology,

and the canadian society of echocardiography. J Am Soc Echocardiogr 2010; 23: 685,713; quiz

786-8.

22. Bamfo JE, Kametas NA, Nicolaides KH, et al. Maternal left ventricular diastolic and systolic long-

axis function during normal pregnancy. Eur J Echocardiogr 2007; 8: 360-8.

23. Vasapollo B, Valensise H, Novelli GP, et al. Abnormal maternal cardiac function and morphology

in pregnancies complicated by intrauterine fetal growth restriction. Ultrasound Obstet Gynecol

2002; 20: 452-7.

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