Bleeding and thrombotic risk in pregnant women with Fontan physiology

Background/objectives Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.  Methods We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.  Results We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33 +/- 5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). Conclusions Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy

Cardiac structure and function during human pregnancy

© 2006 Dr. Dominica ZentnerThis thesis explored, by non-invasive assessment, the cardiovascular function of volunteer participants during the menstrual cycle and pregnancy. In doing so it addresses the potential influences of hormonal variation on the heart and blood vessels. In the case of the post-ovulatory luteal phase of the menstrual cycle and early pregnancy, the predominant hormonal change is increased progesterone. This hormonal similarity raises questions about the degree to which cardiovascular changes might also qualitatively resemble one another in these 2 circumstances, possibly providing a physiological "bridge" between pre- and early pregnancy. This thesis also examines the changes in cardiovascular structure and function between early and late pregnancy, a period of growth for the fetus and a time during which the mother shows features of insulin resistance that might be influenced by pre-pregnancy maternal characteristics such as body weight. This provides an opportunity to assess the relative strength of association between these factors (fetal and maternal) and cardiovascular adaptation. Cardiovascular characteristics were measured longitudinally during the menstrual cycle both before (follicular phase) and after (luteal phase) ovulation. Careful timing of measurement ensured that estradiol levels were stable between the follicular and luteal phase and that progesterone levels increased markedly after ovulation. Nine healthy women had measurements made in two separate cycles that were averaged to minimise individual variation. Although weight did not alter between the follicular and luteal phases, hemoglobin and hematocrit decreased significantly, suggesting an increase in intravascular volume. Supine systolic and diastolic blood pressures were lower during the luteal phase. There was a borderline increase in cardiac output over this period, suggesting a reduction in total peripheral resistance to account for the fall in supine blood pressure. Evidence of homeostatic responses to this vasodilatation included the suggestion of increased sympathetic reactivity (higher blood pressure on standing) and reduced parasympathetic responses (failure to reduce blood pressure with carotid pressure), increased renin and reduced atrial natriuretic peptide. The studies in pregnancy involved 100 healthy women who were assessed in early pregnancy (average of 16 weeks gestation). Thirty two of these women had repeat cardiovascular assessments in late pregnancy (average of 37 weeks gestation). Reflecting an exaggeration of the changes observed between the follicular and luteal phases of the menstrual cycle, in early pregnancy hemoglobin, hematocrit and blood pressure were lower than observed in the women (matched for age, body weight) in the menstrual study. It was observed that the cardiovascular system in early pregnancy was characterised by tachycardia that required a period of rest to reach basal levels. These levels were lower than previously reported. Also in contrast to previous studies, although median cardiac output in early pregnancy was slightly greater than in the menstrual study, this was not statistically significant. The most significant original finding was that at term, a decrease was observed in both systolic and diastolic left ventricular function as measured using modern tissue Doppler methods. These unexpected findings, in otherwise well women, suggest that the stress of pregnancy on the maternal heart is greater than previously appreciated. The diminished functional capacity of the heart was more marked in overweight women. These findings might also provide a clue to the (rare) complication of peripartum cardiomyopathy, a condition known to occur more frequently in overweight/obese women. Findings from this thesis provide new insights into the physiological changes of the cardiovascular system during the menstrual cycle and pregnancy. The studies were undertaken after rest, but in pregnancy especially it would be of interest to examine cardiac performance during activity. Further studies in complicated pregnancies might also clarify whether cardiovascular characteristics are qualitatively or quantitatively different to normal pregnancies. Nevertheless, these studies, which provide normative data on modern cardiovascular phenotypes, might find clinical utility particularly for women during pregnancy complicated by pre-existing cardiac disease or by medical maternal complications of pregnancy. Finally, in a more general sense, the demonstration that maternal weight impacts on cardiovascular function adds strength to the current concerns about excess weight in our community

Cardiac structure and function during human pregnancy

© 2006 Dr. Dominica ZentnerThis thesis explored, by non-invasive assessment, the cardiovascular function of volunteer participants during the menstrual cycle and pregnancy. In doing so it addresses the potential influences of hormonal variation on the heart and blood vessels. In the case of the post-ovulatory luteal phase of the menstrual cycle and early pregnancy, the predominant hormonal change is increased progesterone. This hormonal similarity raises questions about the degree to which cardiovascular changes might also qualitatively resemble one another in these 2 circumstances, possibly providing a physiological "bridge" between pre- and early pregnancy. This thesis also examines the changes in cardiovascular structure and function between early and late pregnancy, a period of growth for the fetus and a time during which the mother shows features of insulin resistance that might be influenced by pre-pregnancy maternal characteristics such as body weight. This provides an opportunity to assess the relative strength of association between these factors (fetal and maternal) and cardiovascular adaptation. Cardiovascular characteristics were measured longitudinally during the menstrual cycle both before (follicular phase) and after (luteal phase) ovulation. Careful timing of measurement ensured that estradiol levels were stable between the follicular and luteal phase and that progesterone levels increased markedly after ovulation. Nine healthy women had measurements made in two separate cycles that were averaged to minimise individual variation. Although weight did not alter between the follicular and luteal phases, hemoglobin and hematocrit decreased significantly, suggesting an increase in intravascular volume. Supine systolic and diastolic blood pressures were lower during the luteal phase. There was a borderline increase in cardiac output over this period, suggesting a reduction in total peripheral resistance to account for the fall in supine blood pressure. Evidence of homeostatic responses to this vasodilatation included the suggestion of increased sympathetic reactivity (higher blood pressure on standing) and reduced parasympathetic responses (failure to reduce blood pressure with carotid pressure), increased renin and reduced atrial natriuretic peptide. The studies in pregnancy involved 100 healthy women who were assessed in early pregnancy (average of 16 weeks gestation). Thirty two of these women had repeat cardiovascular assessments in late pregnancy (average of 37 weeks gestation). Reflecting an exaggeration of the changes observed between the follicular and luteal phases of the menstrual cycle, in early pregnancy hemoglobin, hematocrit and blood pressure were lower than observed in the women (matched for age, body weight) in the menstrual study. It was observed that the cardiovascular system in early pregnancy was characterised by tachycardia that required a period of rest to reach basal levels. These levels were lower than previously reported. Also in contrast to previous studies, although median cardiac output in early pregnancy was slightly greater than in the menstrual study, this was not statistically significant. The most significant original finding was that at term, a decrease was observed in both systolic and diastolic left ventricular function as measured using modern tissue Doppler methods. These unexpected findings, in otherwise well women, suggest that the stress of pregnancy on the maternal heart is greater than previously appreciated. The diminished functional capacity of the heart was more marked in overweight women. These findings might also provide a clue to the (rare) complication of peripartum cardiomyopathy, a condition known to occur more frequently in overweight/obese women. Findings from this thesis provide new insights into the physiological changes of the cardiovascular system during the menstrual cycle and pregnancy. The studies were undertaken after rest, but in pregnancy especially it would be of interest to examine cardiac performance during activity. Further studies in complicated pregnancies might also clarify whether cardiovascular characteristics are qualitatively or quantitatively different to normal pregnancies. Nevertheless, these studies, which provide normative data on modern cardiovascular phenotypes, might find clinical utility particularly for women during pregnancy complicated by pre-existing cardiac disease or by medical maternal complications of pregnancy. Finally, in a more general sense, the demonstration that maternal weight impacts on cardiovascular function adds strength to the current concerns about excess weight in our community

Maternal Loeys–Dietz syndrome (transforming growth factor ligand 2) in a twin pregnancy: Case report and discussion

Loeys–Dietz syndrome is a rare autosomal dominant connective tissue disorder. Pregnant women with Loeys–Dietz syndrome are at increased risk of serious vascular and visceral complications, including aortic dissection and uterine rupture. Multidisciplinary tertiary management aims to mitigate such complications by preconception counselling and vascular assessment, medical therapy, regular echocardiography in pregnancy and joint decision-making re-mode and timing of delivery. We report an in vitro fertilisation twin pregnancy in a woman with Loeys–Dietz syndrome first seen at our institution at 26 weeks’ gestation. After monitoring via serial echocardiograms, caesarean delivery occurred at 30 + 1 weeks’ gestation to allow planned delivery with suspected fetal growth restriction before uterine distension was considered an indication. The patient was discharged on Day 9 with a planned early aortic root replacement due to an increase in diameter from 39 to 43 mm, followed by the discharge of twin boys at term equivalent

Fertility and pregnancy in the Fontan population

Background Women with a Fontan circulation are deemed at significantly increased risk of maternal morbidity and mortality during pregnancy. Publications describe a small number of pregnancies worldwide and a high rate of miscarriage. We compiled the experience of women enrolled in the Australia and New Zealand Fontan (ANZ) Registry with regard to menarche, contraceptive use, pregnancy advice and pregnancy outcomes. Methods Women within the ANZ Fontan Registry were contacted and asked to consent to receiving sequential questionnaires. Results 156 women ≥ 18 years of age (including 4 deceased individuals) were identified, 101 women consented and 97 completed the initial questionnaire. Women were aged (median) 25 years (23–32); menarche occurred at a median 14 years (13–16). A wide variety of contraceptive methods was reported. 81% of women reported having received advice that pregnancy carried an increased risk or was inadvisable. Pregnancy was reported in a minority (n = 27). Miscarriage (42.5%) and termination (7.5%) accounted for half the pregnancy outcomes and the babies were born early (median 31.5 weeks) and small (median 1350 g). Maternal complications of bleeding, arrhythmia and heart failure were reported with no early maternal mortality. Conclusions In women with a Fontan circulation the fertility onset is delayed and pregnancy has a higher rate of miscarriage. Successful pregnancy resulted in small and premature babies. Significant maternal morbidity occurred. Whether pregnancy with its volume loading has an adverse effect on the long-term outcome of women with a single ventricle remains to be elucidated

Heart Disease and Pregnancy: The Need for a Twenty-First Century Approach to Care…

Pregnancy and childbirth present a specific challenge to the maternal cardiovascular system. Pre-existing cardiac diseases, or cardiac diseases that occur during pregnancy, are associated with a significant risk of morbidity and mortality for both mother and baby. In recent decades, cardiac disease has emerged as a leading cause of maternal death in most high income countries, including Australia and New Zealand. The burden of cardiac disease in pregnancy is likely to be growing due to an increase in adult survivors with congenital heart disease embarking on pregnancy coupled with demographic shifts in the age and cardiovascular risk factors of women giving birth and the persisting high incidence of acute rheumatic fever in First Nations women. There is widespread consensus that the best obstetric and neonatal outcomes in women with cardiac disease are delivered by a strategy of carefully coordinated multidisciplinary care. Australia and New Zealand currently lack nationally agreed strategies for clinical practice and service delivery for women with heart disease in pregnancy. This state-of-the-art review summarises some of the key issues faced in relation to prevention, diagnosis, treatment and health service delivery in this patient group and concludes with suggested priorities for policy and research

Atrioventricular valve failure in fontan palliation

BACKGROUND Atrioventricular valve failure (moderate or greater regurgitation, or valve operation) is a risk factor for adverse outcomes in patients undergoing Fontan palliation.OBJECTIVES This study determined the incidence of atrioventricular valve failure and its clinical impact on patients undergoing Fontan palliation.METHODS A retrospective cohort longitudinal study was conducted using patient data extracted from an existing bi-national, population-based registry.RESULTS A total of 1,468 patients who underwent Fontan palliation were identified; complete follow-up data were available for 1,199 patients. Six hundred eighty-six patients had 2 atrioventricular valves, 286 had a single mitral valve, 130 had a common atrioventricular valve, and 97 had a single tricuspid valve. A total of 132 repairs were performed in 110 patients, and 15 replacements were performed in 13 patients, The cumulative incidence of atrioventricular valve failure at 25 years of age for patients with a common atrioventricutar, single tricuspid, single mitral, and 2 atrioventricutar valves was 56% (95% confidence interval [CI]: 46% to 67%), 46% (95% CI: 31% to 61%), 8% (95% CI: 4% to 12%), and 26% (95% CI: 21% to 30%), respectively. In patients without valve failure, freedom from Fontan failure at 10 and 20 years post-Fontan palliation was 91% (95% CI: 89% to 93%) and 77% (95% CI: 73% to 81%), respectively, compared with 77% (95% CI: 69% to 85%) and 54% (95% CI: 42% to 68%), respectively, in patients with valve failure (hazard ratio: 2.43; 95% CI: 1.74 to 3.39; p < 0.001).CONCLUSIONS Atrioventricular valve failure occurs frequently in patients undergoing Fontan palliation. Patients with valve failure are twice as likely to have their Fontan circulation fail than those without valve failure. (C) 2019 by the American College of Cardiology Foundation