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Focus on pregnancy-mediated heart and vascular disease

Year: 2014
Type: article
Abstract: Worldwide, the number of women who have a pre-existing cardiovascular disease (CVD) or develop cardiac problems during pregnancy is increasing, and CVD is the leading cause of non-obstetric mortality during pregnancy. The physiological changes that occur during pregnancy and in the peripartum period provide a challenge to the cardiovascular system of all women and especially to those with previously present cardiovascular conditions. Understanding the morphological and functional changes in normal pregnancy is therefore important for the timely recognition of cardiac pathology during this vulnerable period. However, there is still a lack of evidenced-based clinical data in this field, as well as a deficit in understanding general physiological and pathophysiological processes operating in the maternal heart around pregnancy. CVD around pregnancy thus provides challenges for both the treating physician and the basic scientist. The present Review Focus issue provides a series of reviews and original work, from both expert clinical and basic scientists in the field, which outline the present state of knowledge on critical aspects of pregnancy-mediated heart and vascular disease. Pregnancy poses a significant physiological stress, as haemodynamic changes increase cardiac output, blood volume, and cardiac workload. The review by Chung and Leinwand1 summarizes how the maternal heart specifically reacts to this situation and describes the type of morphological and functional changes that clearly differ from pathological cardiac hypertrophy, as well as from the exercise-induced alterations observed in athletes' hearts. Beside haemodynamic alterations, substantial hormonal changes occur during pregnancy which impact not only on the cardiac muscle but also on the vasculature, including a propensity to blood clotting, haemorrhage, and hypertensive conditions. At the same time, maternal metabolism is also dramatically altered to support the robust energetic needs of the growing foetus, affecting all maternal organs, including the heart. The impact of this highly interesting aspect on the maternal heart is poorly understood and its potential impact is highlighted in the review by Liu and Arany.2 CVD in pregnancy is a complex topic. Women can present either pre- or postpartum, and aetiologies include de novo pathologies or pre-existing heart disease, including congenital heart disease, valvular heart disease, chronic hypertension, or familial dilated cardiomyopathy. In this special issue of CVR, we mainly focus on CVDs that are directly related to pregnancy, such as hypertensive disorders of pregnancy and peripartum cardiomyopathy (PPCM). Pre-eclampsia occurs in 3–5% of all pregnancies and is increasingly recognized as a strong risk factor for CVD decades later. The review by Chen et al.3 focuses on this relationship between pre-eclampsia and CVD, reviewing the epidemiology and discussing possible causal relationships. Sliwa and Boehm4 summarize in their review the current knowledge of the incidence and prevalence of pregnancy-related CVD in women presenting pre- or postpartum. Additional diseases such as PPCM and pregnancy-related myocardial infarction are highlighted in their review, while metabolic aspects of these diseases are discussed by Liu and Arany.2 Sliwa and Boehm4 also describe differences in prevalence and treatment options of pregnancy-related heart diseases worldwide and highlight the problem in developing countries especially in Africa and in Haiti but also in Western Countries where pregnancy-associated heart disease belongs to the most frequent complications in pregnancy. In recent years, the understanding of genetics in CVD has tremendously advanced, and genetic testing has identified many women of child-bearing age who carry potential disease-causing mutations. The current knowledge on the basic clinical aspects, genetics and pregnancy-outcome in women with different types of inherited cardiomyopathies, as well as the genetic aspects of pregnancy-associated cardiomyopathy, including peripartum heart failure, are discussed in the review by van Tintelen et al.5 PPCM is increasingly recognized as an important condition complicating pregnancy, and receives particular attention in the current issue of CVR. The disease is characterized by a sudden onset of heart failure in the last month of pregnancy and in the first months after delivery, associated with a high morbidity and mortality.6–9 A revised definition of PPCM as ‘an idiopathic cardiomyopathy presenting with heart failure secondary to LV systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found’ has recently been published.9 The aetiology of this disease is largely unknown, but its incidence is rising10 making it even more important to understand its underlying pathophysiologies. Over the years, several hypotheses for underlying mechanisms of PPCM have been published, which may include low selenium levels, various viral infections, stress-activated cytokines, inflammation and autoimmune reaction, and a pathological response to haemodynamic stress.8,11 Liu and Arany2 review more recent discoveries on the pathomechanisms, including unbalanced oxidative stress and high levels of the nursing hormone Prolactin (PRL) leading to the production of an angiostatic and pro-apoptotic 16-kDa PRL that together with additional placental anti-angiogenic factors such as sFlt1 seem to initiate and drive the disease.12,13 In addition, novel aspects of PPCM are presented in an original paper by Ricke-Hoch et al.14 involving prolactin and interferon gamma (IFNγ) and high activation of Akt signalling. Inflammatory components as indicated by up-regulation of pro-inflammatory serum markers such as sFas/Apo1, C-reactive protein (CRP), IFNγ, tumour necrosis factor-α (TNFα), and interleukin 6 (IL-6) are prominent in African PPCM patients with a positive correlation of persisting IFNγ, higher prolactin, and increased oxidative stress for an adverse outcome in PPCM.15 Ricke-Hoch et al.14 found that enhanced postpartum Akt activation by circulating IFNγ and prolactin is lowering anti-oxidative defence in the maternal heart, which promotes not only the development of PPCM but also accelerates cardiac inflammation and with this the severity of the disease. Finally, Sliwa and Boehm4 discuss in some detail the current clinical knowledge of this disease. Taken together, the present special Review Focus of Cardiovascular Research on ‘Pregnancy-mediated Heart & Vascular Disease’ assembled by some of the leading experts in the field summarize the current state of knowledge on epidemiology of CVD around pregnancy and provide novel insights into the pathophysiology behind the different disease types and the potential consequences for the clinical management of these patients.
DOI: 10.1093/cvr/cvu032
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W2018892272
FWCI: 0.421
Cites: 15
Cited by: 5
Related to: 10