Cardiac Remodeling After Hypertensive Pregnancy Following Physician-Optimized Blood Pressure Self-Management: The POP-HT Randomized Clinical Trial Imaging Substudy.

BACKGROUND: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling. METHODS: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed. RESULTS: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07-0.05; P<0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m2; 95% CI, -7.99 to -4.74; P<0.001), end-diastolic volume (-3.87 mL/m2; 95% CI, -6.77 to -0.98; P=0.009), and end-systolic volume (-3.25 mL/m2; 95% CI, 4.87 to -1.63; P<0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P<0.001) and 2.8% (95% CI, 1.4-4.1; P<0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P=0.024) and a reduction in left atrial volumes of -4.33 mL/m2 (95% CI, -5.52 to -3.21; P<0.001) between baseline and follow-up when adjusted for baseline differences in measures. CONCLUSIONS: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04273854.

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial.

Importance: Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. Objective: To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum. Design, Setting, and Participants: Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months. Interventions: Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care. Main Outcomes and Measures: The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure. Results: Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001). Conclusions and Relevance: In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK. Trial Registration: ClinicalTrials.gov Identifier: NCT04273854.

Temporal patterns of pre- and post-natal target organ damage associated with hypertensive pregnancy: a systematic review.

AIMS: Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage first emerges could guide optimal timing of preventive interventions. This review identifies evidence of hypertensive target organ damage across cardiac, vascular, cerebral, and renal systems at different time points from pregnancy to postpartum. METHODS AND RESULTS: Systematic review of Ovid/MEDLINE, EMBASE, and ClinicalTrials.gov up to and including February 2023 including review of reference lists. Identified articles underwent evaluation via a synthesis without meta-analysis using a vote-counting approach based on direction of effect, regardless of statistical significance. Risk of bias was assessed for each outcome domain, and only higher quality studies were used for final analysis. From 7644 articles, 76 studies, including data from 1 742 698 pregnancies, were identified of high quality that reported either blood pressure trajectories or target organ damage during or after a hypertensive pregnancy. Left ventricular hypertrophy, white matter lesions, proteinuria, and retinal microvasculature changes were first evident in women during a hypertensive pregnancy. Cardiac, cerebral, and retinal changes were also reported in studies performed during the early and late post-partum period despite reduction in blood pressure early postpartum. Cognitive dysfunction was first reported late postpartum. CONCLUSION: The majority of target organ damage reported during a hypertensive pregnancy remains evident throughout the early and late post-partum period despite variation in blood pressure. Early peri-partum strategies may be required to prevent or reverse target organ damage in women who have had a hypertensive pregnancy.

This review identifies evidence of damage to the heart, brain, and blood vessels during and after hypertensive disorders of pregnancy and compares the pattern of changes that occur to blood pressure variations. Changes in the heart, brain, and blood vessels are first found in women during a hypertensive pregnancy and are also reported early after pregnancy. The majority of target organ damage reported remains evident long after pregnancy despite variation in blood pressure levels.

Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial.

INTRODUCTION: New-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured 6 weeks postpartum predictive of blood pressure 5-10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes. METHODS AND ANALYSIS: POP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a 'smartphone' app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6-9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers. ETHICS AND DISSEMINATION: IRAS PROJECT ID 273353. This trial has received a favourable opinion from the London-Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. TRIAL REGISTRATION NUMBER: NCT04273854.

The Immediate and Long-Term Impact of Preeclampsia on Offspring Vascular and Cardiac Physiology in the Preterm Infant.

Hypertensive disorders of pregnancy, including preeclampsia, affect nearly 10% of all pregnancies and are associated with significant long-term detrimental effects on both maternal and offspring cardiovascular health. Current management of preeclampsia involves timely delivery with the more severe form of disease requiring iatrogenic preterm birth. The effects on the maternal cardiovascular system have been studied extensively; however, less is known about the short- and long-term impacts on offspring cardiovascular health. There is a growing body of evidence suggesting that the offspring of pre-eclamptic pregnancies have an altered cardiac structure and function, along with a unique vascular physiology driven by lower endothelial function. Many of these changes can also be seen in those born preterm even in the absence of pregnancy hypertension. It is difficult to determine the relative contribution of pre-maturity and preeclampsia to the cardiovascular phenotype of those exposed to these pregnancy complications as they are, in many cases, inextricably linked. This review, therefore, focuses specifically on the evidence from clinical studies showing a negative cardiovascular impact of preeclampsia in preterm-born offspring, investigating phenotypic similarities and differences between offspring born preterm to normotensive vs. pre-eclamptic pregnancies. We explore the unique cardiac and vascular alterations in pre-eclamptic offspring born preterm, highlighting knowledge gaps, and potential areas of further research in the field.

Prenatal and Postnatal Cardiac Development in Offspring of Hypertensive Pregnancies.

Background Pregnancy complications such as preterm birth and fetal growth restriction are associated with altered prenatal and postnatal cardiac development. We studied whether there were changes related specifically to pregnancy hypertension. Methods and Results Left and right ventricular volumes, mass, and function were assessed at birth and 3 months of age by echocardiography in 134 term-born infants. Fifty-four had been born to mothers who had normotensive pregnancy and 80 had a diagnosis of preeclampsia or pregnancy-induced hypertension. Differences between groups were interpreted, taking into account severity of pregnancy disorder, sex, body size, and blood pressure. Left and right ventricular mass indexed to body surface area (LVMI and RVMI) were similar in both groups at birth (LVMI 20.9±3.7 versus 20.6±4.0 g/m2, P=0.64, RVMI 17.5±3.7 versus 18.1±4.7 g/m2, P=0.57). However, right ventricular end diastolic volume index was significantly smaller in those born to hypertensive pregnancy (16.8±5.3 versus 12.7±4.7 mL/m2, P=0.001), persisting at 3 months of age (16.4±3.2 versus 14.4±4.8 mL/m2, P=0.04). By 3 months of age these infants also had significantly greater LVMI and RVMI (LVMI 24.9±4.6 versus 26.8±4.9 g/m2, P=0.04; RVMI 17.1±4.2 versus 21.1±3.9 g/m2, P<0.001). Differences in RVMI and right ventricular end diastolic volume index at 3 months, but not left ventricular measures, correlated with severity of the hypertensive disorder. No differences in systolic or diastolic function were evident. Conclusions Infants born at term to a hypertensive pregnancy have evidence of both prenatal and postnatal differences in cardiac development, with right ventricular changes proportional to the severity of the pregnancy disorder. Whether differences persist long term as well as their underlying cause and relationship to increased cardiovascular risk requires further study.