Maternal hemodynamics in hypertensive disorders of pregnancy- a human and animal model under antihypertensive therapy

Hypertensive disorders of pregnancy (HDP) have been the leading cause of maternal and neonatal morbidity and mortality worldwide over the last decades. Recently, the common belief of preeclampsia (PE), defined as an increased blood pressure and organ dysfunction such as protein loss after 20 weeks of gestation, being a placental disorder was challenged. A number of studies reported short and long term cardiovascular changes in pregnancies affected by HDP suspecting a cardiovascular origin of the disease. Impaired cardiac output, increased systemic vascular resistance and diastolic ventricular dysfunction- signs for impaired cardiac function- were detected by ultrasound evaluation of the maternal heart. Even though there are new insights into the origin of the disease, the concepts of therapy have not changed. Evidence for an improvement by antihypertensive therapy in women with HDP reflected by a decrease in adverse maternal and neonatal outcome is lacking, except for reduced risk for maternal cerebral hemorrhage. Therefore we aim to investigate maternal hemodynamics and cardiovascular parameters in women with HDP compared to a healthy pregnant control group matched for gestational age and in a preeclamptic rat model, with the special focus on changes in maternal hemodynamics due to antihypertensive treatment that has not been accessed in this specific setting before. In this prospective observational case control study over a three-year period we challenge the idea of blood pressure being the suitable target for antihypertensive therapy in women with HDP and aim to get new insights into the pathophysiology of the disease by using invasive procedures and assessing the structural morphology of the heart in our rat model. During the third year (covering the period from July 1st, 2021 to June 30th, 2022) of our study, we conducted research activities according to study protocol and progress plan. Specifically eligible pregnant women have been recruited and followed-up, in vivo animal studies commenced and laboratory proceedings for analyses of blood samples for placenta associated biomarkers as well as first analyses have been conducted at the respective study sites. Our collaboration has resulted in a first research publication covering tissue- and biomarker based investigations of the specific kidney damage occurring in preeclampsia in a rat model of the disease, both during and after pregnancy. Another original research article concerning the study design and expected results has been submitted to an international, peer-reviewed journal. The Corona virus pandemic has repeatedly lead to a full stop of all research activities (both patient recruitment, experimental work with animals and access to laboratory facilities) at all study sites, and the consequences are still present as delays in research progress.

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Hypertensive disorders of pregnancy (HDP) have been the leading cause of maternal and neonatal morbidity and mortality worldwide in the last decades. Recently, the common belief of preeclampsia (PE), defined as hypertension and proteinuria after 20 weeks of gestation, being a placental disorder was challenged. A number of studies reported short and long term cardiovascular changes in pregnancies affected by HDP suspecting a cardiovascular origin of the disease. Impaired cardiac output (CO), increased systemic vascular resistance and diastolic ventricular dysfunction were detected by echocardiography. Even though there are new insights into the pathophysiology of the disease, the concepts of therapy have not changed. Evidence for an improvement of antihypertensive therapy in women with HDP reflected by a decrease in adverse maternal and neonatal outcome is lacking. Therefore we aim to investigate maternal hemodynamics and cardiovascular parameters in women with HDP compared to a healthy pregnant control group matched for gestational age and in a preeclamptic rat model, with the special focus on changes in maternal hemodynamics due to antihypertensive treatment that has not been accessed in this specific setting before. In this prospective observational case control study over a three-year period we challenge the idea of blood pressure being the suitable target for antihypertensive therapy in women with HDP and aim to get new insights into the pathophysiology of the disease by using invasive procedures and assessing the structural morphology of the heart in our rat model.