The bench is the bedside – the role of transthoracic echocardiography in translating pregnancy research into clinical practice

The World Health Organization's Millennium Development Goal 5 has two objectives. The first aims to reduce the maternal mortality ratio by three quarters between 1990 and 2015. The second aims to achieve, by 2015, universal access to reproductive health 1. Whilst some significant progress has been made in these areas, the rate of progress is slow and it is unlikely that these goals will be achieved within the timeframe proposed. Concurrently, it has been proposed that in order to reduce mortality, access to high-quality reproductive care is needed, as well as the implementation of effective interventions. In countries where maternal mortality is already low and where women have access to reproductive healthcare, significant maternal morbidity remains high. It is estimated that short-term severe maternal morbidity, defined as ‘a woman who nearly died but survived a complication that occurred during pregnancy, childbirth or within 42 days of termination of pregnancy' occurs in approximately 1 in 200 pregnant women 2-4. Long-term morbidity is more difficult to estimate; however, population-based work, especially examining the effect of severe pre-eclampsia on long-term maternal health, suggests that long-term adverse maternal cardiovascular health outcomes may be significant 5. Despite access to high-quality maternity care in many countries, pregnant women still suffer significant pregnancy-related morbidity. Two reasons may help to explain why this is the case. The first is that the recognition and diagnosis of some of the most common and significant diseases of pregnancy still remain suboptimal 6. Obstetric critical illnesses such as cardiac failure, severe complications of pre-eclampsia, obstetric haemorrhage and sepsis are sometimes poorly recognised, leading to morbidity and mortality 7, 8. In many situations, there appears to be a failure to appreciate and/or observe abnormal clinical symptoms and signs, as well as a failure to translate the known physiological and pathophysiological processes underlying these critical illnesses into the clinical management at the bedside. The second reason relates to the choice of effective treatment interventions. Informed decision-making regarding interventions is often difficult since randomised controlled trials of pharmacological interventions may not have been performed to address the clinical question. Effective treatment is further impacted upon by the more fundamental problem of poor understanding of the basic pathophysiology of some significant diseases of pregnancy, such as pre-eclampsia. Rational therapeutic choices are sometimes based on very limited research or extrapolated from non-pregnant populations. The most recent H1N1 pandemic informed us that such assumptions may lead to poorer outcomes for pregnant women, as the pharmacology of specific therapeutic agents may not have been studied in this group. This pandemic and its effect on pregnant women provided an impetus for change in this area, and raised awareness of the need to include pregnant women in appropriate research studies both on scientific and ethical grounds 9. A step towards effective solutions to clinical problems and reducing the global burden of pregnancy-related diseases is to be able to translate the pregnancy research that is done into changes in clinical practice. One of the significant problems regarding research is that it may not be translatable to clinical practice. Specifically in the area of pregnancy research, the scientific questions posed by researchers need to be relevant to pregnant women, and the methodologies used to answer the scientific questions need to be applicable to pregnant women. The terms ‘translational research’, ‘translational medicine’ and ‘bench-to-beside research’ form part of an entire medical lexicon used to describe the processes by which medical research can be made directly related to improvements in health. The terminology exists because of the recognised great divide between research, often laboratory- or bench-based, and subsequent beneficial changes in clinical practice. Such is the size of the gulf that an article describing it in Nature in 2008 was entitled Translational research: crossing the valley of death 10. In order to be translational, solutions to problems provided by research need to be effective and safe in clinical practice, ethical 11, of lower risk than no intervention and acceptable to women. Not only does the clinical question need to be answered by the research, but the technique by which it was answered also needs to be feasible, relevant and applicable to people, not animals, and therefore translatable to clinical practice. Much of the anaesthesia and critical care research exploring cardiac physiology, including responses to disease processes, pharmacological interventions and intravenous fluid, has the ability to bridge the divide between the bench and the bedside. In this sphere, transthoracic echocardiography stands out as an invaluable measuring tool because it has the ability to demonstrate visually and quantify cardiac function, thereby breaking down the barriers between laboratory-based and clinical-based research. Traditionally, it has been difficult to make precise, detailed and accurate observations regarding the pathophysiology of cardiovascular diseases in pregnant women because the measurement devices have not been easily transportable or have been invasive with known complications and risks. Recent advances in portability, accessibility and image quality now mean that transthoracic echocardiography can be used in the pregnancy research setting to provide detailed observations at the point of patient care. This is an important step forward because it coincides with the emergence of cardiovascular disease as the most common cause of death in countries with low overall maternal mortality 6. In addition, deaths from pre-eclampsia, a hypertensive cardiovascular system disease of pregnancy, remain static with no reductions in mortality for over a decade 6. The use of transthoracic echocardiography as a research tool compliments its clinical application in pregnant women and may therefore be able to bridge the divide between experimental research work and clinical practice. In cardiovascular medicine, transthoracic echocardiography is widely used as a diagnostic and management tool 12, 13. Its role as a research tool is also well established 14, 15. Its use by anaesthetists, emergency physicians and intensive care specialists in the clinical setting is increasing 16-22. As well as a clinical tool in pregnant women 23-26, the application of transthoracic echocardiography as a research tool has significant advantages in pregnant women 27. It is non-invasive, safe, does not alter underlying physiology and is acceptable to pregnant women. It provides accurate, functional and structural cardiac physiological and pathological data. In this setting, there are no other comparable devices. The scientific integrity of the observations made to study diseases of pregnancy is facilitated by the very nature of how we manage pregnant women. Management involving general anaesthesia and mechanical ventilation is usually avoided, sedation is rarely used and pharmacological interventions are limited to essential medications. Therefore, many of the observations reflect pure disease states. Furthermore, the thoracic anatomical changes of pregnancy and the requirement for left lateral positioning mean that many of the limitations of transthoracic echocardiography do not exist when the technology is applied in the research and clinical settings in pregnant women 28. Translation of the information obtained from bedside echocardiography research into clinical practice is facilitated by the role that echocardiography can play in enabling bedside education. When research is performed in the clinical setting, there are opportunities to teach health professionals, including medical students, at the bedside. Women and their families participate in both the research and educational opportunities. The very occurrence of bedside research affirms the feasibility of the technique in the hospital setting. In turn, a research culture is developed and many staff become engaged in the process of change. Although translation of transthoracic echocardiography research to clinical practice has occurred, the application of bedside echocardiography in clinical practice is still an emerging technique and the uptake of bedside echocardiography is by no means universal. Despite its advantages, transthoracic echocardiography is not currently routinely used in anaesthetic practice; it is not yet considered a mandatory monitoring device and it is rarely incorporated into the teaching curriculum. Increasing the uptake of echocardiography will involve the dual approach of universal education and research into abbreviated and rapid scanning protocols, combined with individual departmental echocardiography programmes that incorporate quality assurance, data storage and study review. Echocardiography education fundamentally involves real-time observation of cardiac physiology and pathophysiology. Incorporating this education into undergraduate and postgraduate teaching programmes, as well as programmes in schools, will enable future health professionals to understand what questions can be answered with this technology and how to use it. Research examining abbreviated scanning protocols and the impact they have on clinical decision-making will enable a rationalisation of, and validation for, specific echocardiographical measurements as well as the generation of protocols and guidelines in this area. Echocardiography is not currently utilised routinely, but given that it has the ability to demonstrate contractility and measure diastolic function and left ventricular end-diastolic diameter, the use of transthoracic echocardiography in women with pre-eclampsia in whom antihypertensive therapy, magnesium sulphate and intravenous fluids are being considered may be something that eventually becomes routine. Furthermore, it is not too fanciful to imagine that in the future, women during their pregnancy will undergo scheduled transthoracic echocardiography examinations as well as scheduled abdominal ultrasound examinations. Research, by its very nature, is innovative. The application of the scientific method requires perseverance and strict adherence to its principles. It does not predispose an outcome or a location in which it is done. Unlike following a prescribed curriculum, research follows an undetermined and ill-defined path, driven predominately by scientific observations. As such, clinical questions still exist and scientific observations still need to be made in the area of obstetric critical illness. Serious conditions such as cardiac disease, pre-eclampsia, obstetric haemorrhage and sepsis all have a significant impact in terms of morbidity and mortality on pregnant women and their families, and research needs to be tailored to the requirements of pregnant women and the clinical environment. The confluence of high-quality diagnostic and measurement devices enabling scientific observations, a hospital environment, researchers and sick women means that when examining the cardiovascular system in pregnant women using echocardiography, the paradigm can be shifted. In this situation, the bench is the bedside and there is no loss in translation. No external funding or competing interests declared.