Explore the vast range of titles available.

Cardiovascular disease complicates 1–4% of pregnancies — with a higher prevalence when including hypertensive disorders — and is the leading cause of maternal death. In women with known cardiovascular pathology, such as congenital heart disease, timely counselling is possible and the outcome is fairly good. By contrast, maternal mortality is high in women with acquired heart disease that presents during pregnancy (such as acute coronary syndrome or aortic dissection). Worryingly, the prevalence of acquired cardiovascular disease during pregnancy is rising as older maternal age, obesity, diabetes mellitus and hypertension become more common in the pregnant population. Management of cardiovascular disease in pregnancy is challenging owing to the unique maternal physiology, characterized by profound changes to multiple organ systems. The presence of the fetus compounds the situation because both the cardiometabolic disease and its management might adversely affect the fetus. Equally, avoiding essential treatment because of potential fetal harm risks a poor outcome for both mother and child. In this Review, we examine how the physiological adaptations during pregnancy can provoke cardiometabolic complications or exacerbate existing cardiometabolic disease and, conversely, how cardiometabolic disease can compromise the adaptations to pregnancy and their intended purpose: the development and growth of the fetus.In this Review, Roos-Hesselink and colleagues describe how the physiological adaptations during pregnancy can induce cardiometabolic complications or an exacerbation of existing cardiometabolic disease, and discuss the epidemiology, pathophysiology, diagnosis and management of cardiometabolic diseases acquired or presenting during pregnancy, including hypertensive disorders, gestational diabetes mellitus, thromboembolic disorders and peripartum cardiomyopathy.

Effect of pregnancy on microvascular complications in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. Diabetes Control and Complications Trial Research Group Abstract OBJECTIVE: To assess the effect of pregnancy on the development and progression of retinopathy and microalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted longitudinal analyses of the Diabetes Control and Complications Trial (DCCT), a multicenter controlled clinical trial that compared intensive treatment with conventional diabetes therapy and studied 180 women who had 270 pregnancies and 500 women who did not become pregnant during an average of 6.5 years of follow-up. Women assigned to the conventional treatment group were changed to intensive therapy if they were planning pregnancy or as soon as possible after conception. Fundus photography was performed every 6 months, and the urinary albumin excretion rate (AER) was measured annually. RESULTS: Compared with nonpregnant women, pregnant women had a 1.63-fold greater risk of any worsening of retinopathy from before to during pregnancy (P < 0.05) in the intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not pregnant women in the conventional group (P < 0.001). In the conventional group, the odds of > or =3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during pregnancy in the intensive group, but not in the conventional group, was significantly elevated from the level at baseline, albeit in the normal range. Although individual patients had transient worsening of retinopathy during pregnancy, even to the proliferative level, at the end of the DCCT, mean levels of retinopathy and albuminuria in subjects who had become pregnant were similar to those in subjects who had not become pregnant within each treatment group. CONCLUSIONS: Pregnancy in type 1 diabetes induces a transient increase in the risk of retinopathy; increased ophthalmologic surveillance is needed during pregnancy and the first year postpartum. The long-term risk of progression of early retinopathy and albumin excretion, however, does not appear to be increased by pregnancy.

Aims/hypothesis The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabetes. We report the experience from DIRECT (DIabetic REtinopathy and Candesartan Trials), three placebo-controlled studies designed to examine the effects of an ARB, candesartan, on diabetic retinopathy. Methods Over 4 years or longer, 178 normotensive women with type 1 diabetes (86 randomised to candesartan, 32 mg once daily, and 92 assigned to placebo) became pregnant (total of 208 pregnancies). Results More than half of patients were exposed to candesartan or placebo prior to or in early pregnancy, but all discontinued it at an estimated 8 weeks from the last menstrual period. Full-term pregnancies (51 vs 50), premature deliveries (21 vs 27), spontaneous miscarriages (12 vs 15), elective terminations (15 vs 14) and other outcomes (1 vs 2) were similar in the candesartan and placebo groups. There were two stillbirths and two ‘sick babies’ in the candesartan group, and one stillbirth, eight ‘sick babies’ and one cardiac malformation in the placebo group. Conclusions/interpretation The risk for fetal consequences of ARBs in type 1 diabetes may not be high if exposure is clearly limited to the first trimester. Long-term studies in fertile women can be conducted with ARBs during pregnancy, provided investigators diligently stop their administration upon planning or detection of pregnancy. Trial registration ClinicalTrials.gov DIRECT-Prevent 1 NCT00252733; DIRECT-Protect 1 NCT00252720; DIRECT-Protect 2 NCT00252694. Funding The study was funded jointly by AstraZeneca and Takeda.

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. 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. 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.

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. Evidence from mice and humans indicates that peripartum cardiomyopathy (PPCM) is a vascular disease caused by excessive anti-angiogenic signalling in the peripartum period of pregnancy and that pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. Heart disease in pregnancy The cause of a form of heart disease called peripartum cardiomyopathy (PPCM), which can affect women late in pregnancy and after giving birth, has proved elusive. Zoltan Arany and colleagues now show, using an innovative mouse model and human studies, that PPCM is a vascular disease, caused by angiogenic imbalances triggered by pregnancy. A mouse model lacking the transcriptional coactivator PCG-1α in cardiac tissue displays a phenotype similar to PPCM. The authors propose a two-hit mechanism for the condition, in which the anti-angiogenic signalling during late pregnancy combines with an underlying susceptibility caused by insufficient pro-angiogenic defences in the heart. This work offers a possible explanation for the observed link between PPCM and pre-eclampsia, and points to possible pro-angiogenic treatments for the condition, such as recombinant human VEGF121.

The maternal cardiovascular system undergoes dramatic remodeling in response to the stresses of pregnancy. Although in most cases these changes are temporary and well tolerated, in others they can give rise to complications, including cardiomyopathy, coronary artery disease, and hypertensive cardiovascular disease. Despite an increasing number of preclinical models to study these diseases, specific treatments for any of these pregnancy complications are lacking. As the maternal mortality rate is rising in the United States, it is critical to understand the molecular mechanisms driving cardiovascular changes during pregnancy, and the pathology that can result.

Peripartum cardiomyopathy is increasingly recognised and diagnosed in clinical practice. Over the past two decades, a substantial amount of new knowledge on this condition has been accrued, including a better understanding of the pathophysiology, genetic predisposition for a proportion of patients, diagnostic tools, management with a disease-specific therapy, and predictors of outcome. Peripartum cardiomyopathy occurs globally in all ethnic groups and should be suspected in any women who are peripartum presenting with symptoms and signs indicative of heart failure towards the end of pregnancy or in the months following delivery. Verification of left ventricular systolic dysfunction (ejection fraction <45%) is crucial for the diagnosis of peripartum cardiomyopathy and the exclusion of other causes of heart failure, such as pre-existing cardiomyopathy, valvular heart disease, or congenital heart disease. Peripartum cardiomyopathy is a disease with considerable maternal and neonatal morbidity and mortality, with only half of women experiencing complete myocardial recovery within 6 months of the onset of symptoms. This Seminar summarises current knowledge of peripartum cardiomyopathy genetics, pathophysiology, diagnostic approaches, medical management, and outcome. Furthermore, we provide guidance on both risk stratification by use of a novel score to predict recovery and on the outcomes of a subsequent pregnancy.

Cardiovascular disease is a major non-communicable disease globally, with increasing prevalence, posing a significant public health challenge. It is the leading non-obstetric cause of perinatal morbidity and mortality, with a substantial number of cardiac fatalities occurring in individuals without any known pre-existing cardiovascular disease. Peripartum cardiomyopathy is a type of de novo heart failure that occurs in pregnant women in the late stages of pregnancy or following delivery. Despite extensive research, diagnosing and managing peripartum cardiomyopathy remains challenging, resulting in significant morbidity and mortality. Recent advancements and novel approaches have been made to better understand and manage peripartum cardiomyopathy, including molecular and non-molecular biomarkers, genetic predisposition and risk prediction, targeted therapies, multidisciplinary care, and improved patient education. This narrative review provides a comprehensive overview and new perspectives on peripartum cardiomyopathy, covering its epidemiology, updated pathophysiological mechanisms, diagnosis, management, and future research directions for healthcare professionals, researchers, and clinicians.

Key Points Peripartum cardiomyopathy (PPCM) is defined as idiopathic systolic dysfunction in peripartum women To make a diagnosis of PPCM, other possible causes of heart failure in peripartum women, such as genetic forms of dilated cardiomyopathy, need to be excluded The incidence and prognosis of PPCM vary according to socioeconomic and genetic factors The aetiology of PPCM is unknown; risk factors might include pre-eclampsia, twin pregnancies, and African ethnicity A possible pathophysiological mechanism for PPCM is the production of a 16 kDa fragment of prolactin; blocking prolactin is, therefore, a potential therapeutic target Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition that affects women in the final stages of pregnancy or shortly after birth. The underlying pathophysiology of PPCM is incompletely understood. In this Review, Hilfiker-Kleiner and Sliwa summarize the epidemiology of this condition, the current understanding of its aetiology and risk factors, and propose novel biomarkers and treatment strategies for women with PPCM. Cardiovascular diseases are a major cause of complications in pregnancy worldwide, and the number of patients who develop cardiac problems during pregnancy is increasing. Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that emerges towards the end of pregnancy or in the first months postpartum, in previously healthy women. Symptoms and signs of PPCM are similar to those in patients with idiopathic dilated cardiomyopathy. The incidence varies geographically, most likely because of socioeconomic and genetic factors. The syndrome is associated with a high morbidity and mortality, and diagnosis is often delayed. Various mechanisms have been investigated, including the hypothesis that unbalanced peripartum or postpartum oxidative stress triggers the proteolytic cleavage of the nursing hormone prolactin into a potent antiangiogenic, proapoptotic, and proinflammatory 16 kDa fragment. This theory provides the basis for the discovery of disease-specific biomarkers and promising novel therapeutic targets. In this Review, we describe the latest understanding of the epidemiology, pathophysiology, and novel treatment strategies for patients with PPCM.