Elsevier

American Heart Journal

Volume 161, Issue 2, February 2011, Pages 269-275.e1
American Heart Journal

Trial Design
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

https://doi.org/10.1016/j.ahj.2010.10.024Get rights and content

Background

Previous research has shown that women with congenital heart disease (CHD) are more susceptible to cardiovascular, obstetric, and offspring events. The causative pathophysiologic mechanisms are incompletely understood. Inadequate uteroplacental circulation is an important denominator in adverse obstetric events and offspring outcome. The relation between cardiac function and uteroplacental perfusion has not been investigated in women with CHD. Moreover, the effects of physiologic changes on pregnancy-related events are unknown. In addition, long-term effects of pregnancy on cardiac function and exercise capacity are scarce.

Methods

Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) II, a prospective multicenter cohort study, investigates changes in and relations between cardiovascular parameters and uteroplacental Doppler flow patterns during pregnancy in women with CHD compared to matched healthy controls. The relation between cardiovascular parameters and uteroplacental Doppler flow patterns and the occurrence of cardiac, obstetric, and offspring events will be investigated. At 20 and 32 weeks of gestation, clinical, neurohumoral, and echocardiographic evaluation and fetal growth together with Doppler flow measurements in fetal and maternal circulation are performed. Maternal evaluation is repeated 1 year postpartum.

Implications

By identifying the factors responsible for pregnancy-related events in women with CHD, risk stratification can be refined, which may lead to better pre-pregnancy counseling and eventually improve treatment of these women.

Section snippets

Background

Because of improved long-term survival, most women with congenital heart disease (CHD) reach child-bearing age and many pursue pregnancy. In women with uncorrected maternal congenital heart defects or with residual sequelae after correction, the hemodynamic changes in pregnancy can have negative effects on the health of both mother and her (unborn) child. Cardiac events are rare in healthy women (<1%), while arrhythmias occur in 4.5% and heart failure in 4.8% of women with CHD.1 In complex CHD,

Study objectives

The primary objective of the present study is to compare cardiovascular, neurohumoral, and uteroplacental Doppler flow changes during pregnancies of women with CHD with age- and parity-matched healthy controls and to relate these changes to the occurrence of cardiovascular and obstetric events and to offspring outcome. The secondary objective of this study is to evaluate the incidence of permanent postpartum cardiovascular deterioration in women with CHD.

Study design

This is an observational prospective

Discussion

In the present study, we assess whether changes in cardiovascular, hemodynamic, neurohumoral parameters, and uteroplacental Doppler flow patterns during pregnancy of women with CHD differ from age- and parity-matched healthy controls. We also assess the interaction of these changes with the occurrence of cardiovascular, obstetric, and offspring events. In addition, we evaluate the incidence of permanent changes in cardiovascular parameters 1 year postpartum in women with CHD and compare these

Conclusion

The current ZAHARA II study is the first “in vivo” study in women with CHD to evaluate the effect of compromised cardiac performance on the uteroplacental circulation and its relationship with the occurrence of obstetric events and adverse offspring outcome. By identifying the components responsible for pregnancy-related events in women with CHD, we will refine risk stratification that will lead to better pre-pregnancy counseling and may eventually improve treatment of these women.

References (42)

  • DuvekotJ.J. et al.

    Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone

    Am J Obstet Gynecol

    (1993)
  • WilsonM. et al.

    Blood pressure, the renin-aldosterone system and sex steroids throughout normal pregnancy

    Am J Med

    (1980)
  • van OppenA.C. et al.

    Cardiac output in normal pregnancy: a critical review

    Obstet Gynecol

    (1996)
  • GiannakoulasG. et al.

    Usefulness of natriuretic peptide levels to predict mortality in adults with congenital heart disease

    Am J Cardiol

    (2010)
  • DurackD.T. et al.

    New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service

    Am J Med

    (1994)
  • SiuS.C. et al.

    Prospective multicenter study of pregnancy outcomes in women with heart disease

    Circulation

    (2001)
  • DrenthenW. et al.

    Predictors of pregnancy complications in women with congenital heart disease

    Eur Heart J

    (2010)
  • DrenthenW. et al.

    Risk of complications during pregnancy after Senning or Mustard (atrial) repair of complete transposition of the great arteries

    Eur Heart J

    (2005)
  • AardemaM.W. et al.

    Doppler ultrasound screening predicts recurrence of poor pregnancy outcome in subsequent pregnancies, but not the recurrence of PIH or preeclampsia

    Hypertens Pregnancy

    (2000)
  • GerretsenG. et al.

    Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation

    Br J Obstet Gynaecol

    (1981)
  • KhairyP. et al.

    Pregnancy outcomes in women with congenital heart disease

    Circulation

    (2006)
  • Cited by (29)

    • Doppler gradients, valve area and ventricular function in pregnant women with aortic or pulmonary valve disease: Left versus right

      2020, International Journal of Cardiology
      Citation Excerpt :

      All the participating centers received approval of the medical ethics committee and all women (prospectively enrolled) provided written informed consent. The healthy controls were recruited from low risk midwife practices in Groningen and Rotterdam [7]. For the healthy controls, postpartum echocardiograms were also used as baseline measurements.

    • Biological versus mechanical heart valve prosthesis during pregnancy in women with congenital heart disease

      2018, International Journal of Cardiology
      Citation Excerpt :

      Pregnancy related complications were collected for all pregnancies and analyzed for completed pregnancies and defined as occurring during pregnancy and up to 6 months postpartum. Pregnancy related complications were defined in accordance with our previous studies and according to guidelines [20,22,23]. We collected prosthesis related cardiovascular complications (including valve deterioration, valve thrombosis, embolism, hemorrhage, endocarditis and hemolytic anemia), other cardiovascular complications (including need for urgent invasive non-prosthesis related cardiovascular procedures, heart failure or arrhythmias requiring (change of) treatment, myocardial infarction, intensive care or coronary care unit (IC/CCU) admission).

    • Pregnancy in women with corrected aortic coarctation: Uteroplacental Doppler flow and pregnancy outcome

      2017, International Journal of Cardiology
      Citation Excerpt :

      Primary cardiovascular events were defined as: need for an urgent invasive cardiovascular procedure, heart failure (according to the guidelines of the European Society of Cardiology and documented by the attending physician [15]), new onset or symptomatic tachy- or bradyarrhythmia requiring new or extended treatment, thromboembolic events, myocardial infarction, cardiac arrest, cardiac death, endocarditis and aortic dissection [6,7]. Primary obstetric events included: instrumental vaginal delivery (vacuum or forcipal-extraction), Cesarean section (planned or emergency), pregnancy induced hypertension (PIH), pre-eclampsia (PIH combined with proteinuria), eclampsia (pre-eclampsia with grand mal seizures), gestational Diabetes Mellitus, HELLP syndrome (haemolysis, elevated liver enzymes, low platelet syndrome), hyperemesis gravidarum, non-cardiac death, placental abruption, postpartum hemorrhage, preterm labour and preterm premature rupture of membranes (before 37 weeks gestation) [6]. Offspring events were fetal death (intra-uterine death ≥ 20 weeks gestation), perinatal death (number of stillbirths from 20 weeks gestation and death up to 28 days post-partum), intra-ventricular hemorrhage, neonatal respiratory distress syndrome, preterm birth (before 37 weeks gestation), occurrence of congenital heart disease, small for gestational age (birth weight < 10th percentile) and low birth weight (< 2500 g) [6,7].

    • Cardiac function and cardiac events 1-year postpartum in women with congenital heart disease

      2015, American Heart Journal
      Citation Excerpt :

      All echocardiographic recordings were evaluated off-line by 4 experienced cardiologists, blinded to the end points. Chamber quantification, valvular function, and systolic and diastolic ventricular function assessment were performed according to the current recommendations as previously described.13 Cardiovascular events (>6 months after delivery) were assessed during the follow-up visit 1-year postpartum.

    View all citing articles on Scopus

    This study is supported by a grant from the Netherlands Heart Foundation (NHF) (2007B75). DJvV is clinically established investigator of the NHF (D97-017). The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents.

    k

    On behalf of the ZAHARA-II investigators. See the online Appendix for complete listing

    View full text