Remote Patient Monitoring for Chronic Hypertension During Pregnancy (REACH)

Hypotheses / Research Question(s) Specific Aim 1: To evaluate whether remote patient blood pressure monitoring during the antepartum period for patients with chronic hypertension will improve composite perinatal outcomes. Hypothesis: In patients with chronic hypertension, tight blood pressure control with remote patient monitoring will improve composite outcomes. Participants in the two trial arms will be compared for the frequency of composite perinatal outcomes (perinatal death, placental abruption, superimposed preeclampsia with severe features, or indicated preterm birth \<35 weeks). Compliance with the assigned study group will also be assessed.

Specific Aim 2: Assess the impact of remote patient monitoring for chronic hypertension during pregnancy on changes in cardiac strain. Hypothesis: Tight blood pressure control using remote patient monitoring will decrease maladaptive cardiac remodeling during late gestation, which will persist into the postpartum period. Cardiac strain will be assessed using speckle-tracking echocardiography at enrollment and 34 to 36 weeks of gestation.

Exploratory Aim: To compare the accuracy of OB/GYN-derived Point of Care Ultrasound (POCUS) cardiac strain assessments and diastolic parameters to the echocardiogram-derived assessment, we will seek to determine if POCUS images obtained by a physician without echocardiogram training will produce reliable results compared to those obtained with an echocardiogram.

Research Significance Chronic hypertension is defined as preexisting hypertension (\>=140/90 mmHg) diagnosed before 20 weeks' gestation.1 In the United States, 2-6% of all pregnancies are complicated by chronic hypertension, resulting in up to 260,000 births to women with chronic hypertension each year.1-3 There is an increasing number of patients with chronic hypertension during pregnancy,4 and chronic hypertension disproportionally impacts Black pregnant women compared to their White counterparts.5 Of those with chronic hypertension, 25-30% will develop superimposed preeclampsia with severe features.1 Additional adverse outcomes for chronic hypertension in pregnancy are substantial and include small for gestational age birth, abruption, preterm birth, and perinatal death.1,6 Chronic hypertension in pregnancy is associated with an increased risk of superimposed preeclampsia (incidence 25-30%, relative risk compared to no chronic hypertension 3-4),2,7-10 placental abruption (incidence 1.5%, relative risk 2-3),1,2,10 preterm birth before 35 weeks (incidence 18-22%, relative risk 3-4),1,3,7,9,11 and perinatal death (incidence 6-8%, relative risk 3-5).1,2,10 Recently, Tita et al.6 published the Chronic Hypertension and Pregnancy (CHAP) randomized trial of 2,408 pregnant patients with chronic hypertension. This trial showed a 21% decrease in preeclampsia by targeting a blood pressure goal of less than 140/90 mmHg. This study was conducted using in-office blood pressure measurements to titrate medication.6 Whether using home blood pressure readings to optimize treatment further improves clinical outcomes is unknown. Of the patients in the active treatment arm (n=1170), 30.2% had one of the composite primary outcomes compared to 37.0% in the control arm (n=1155). More specifically, preeclampsia with severe features occurred in 23.3%, medically indicated preterm birth before 35 weeks occurred in 12.2%, placental abruption occurred in 1.7%, and fetal or neonatal death before 28 days of life occurred in 3.5%.6 Despite the clinically meaningful reduction in the primary outcome of the CHAP trial, it is unknown if remote patient monitoring can further decrease these adverse maternal and neonatal outcomes.

With the growth of remote clinical monitoring, many patients with chronic hypertension take their blood pressure outside of a medical setting. The United States Preventive Services Task Force recommends confirmation of hypertension outside of pregnancy based on out-of-office blood pressure measurements.1 The decision to treat hypertension based on out-of-office blood pressure measurements is complicated by the fact that studies have shown that non-pregnant patients have home blood pressure measurements that are 5-15 mmHg lower than in-office readings.13 Nevertheless, studies in nonpregnant patients have shown improved blood pressure control with 12 months of remote patient monitoring versus standard treatment alone (72% versus 57%).14 If treating in-office blood pressure readings alone, it may lead to overtreatment in some patients and missed opportunities for medication titration in others.

It is unknown whether remote patient monitoring with a validated blood pressure target and medication titration protocol can further improve outcomes during pregnancy. It is also unknown if home blood pressure readings differ from in-office blood pressures, similar to nonpregnant patients. Previous studies have not shown the benefits of home blood pressure monitoring, but they lack a standardized treatment protocol and depend on individual physician judgment when making medication adjustments.15 In a randomized trial of 850 patients with hypertension, a few of whom had chronic hypertension (n=54), the authors showed a trend toward more preeclampsia diagnoses and frequent induction of labor in those with increased monitoring.16 In more than half of the patients without preexisting hypertension, elevated blood pressures were noted a month before the diagnosis of hypertension using this passive approach to monitoring.17 Notably, this study was performed before the publication of CHAP and lacked the rigorous protocol for blood pressure medication titration that is now available. To our knowledge, there has been no randomized trial of remote patient monitoring versus standard-of-care for treating mild chronic hypertension (\>=140/90 mmHg) during pregnancy.

Speckle tracking echocardiography evaluates the cardiac chamber for thickening or shortening by placing myocardial speckles and tracking the motion of the cardiac chamber.18,19 Naqvi et al. have published cardiac strain outcomes in 45 healthy patients throughout pregnancy. They found that during the third trimester, the strain of all cardiac chambers decreased, and normal values for patients were published in each trimester. In these healthy pregnant individuals, an increase in intraventricular wall thickness, left ventricular mass, and left ventricular end-diastolic diameter was also noted.20 There has been limited speck tracking performed on patients with hypertensive disorders in pregnancy. A study of 85 preeclamptic patients found an increased left atrial volume index compared to normotensive patients.21 In non-pregnant patients, it has been shown to predict cardiovascular outcomes. Global peak atrial longitudinal strain assessed by speckle tracking has been shown to predict cardiovascular events (area under the receiver operator characteristic curve 0.83).22,23 By evaluating cardiac strain, we can determine if interventions during pregnancy have a protective cardiovascular effect.

Historically, most studies of antihypertensive medications have focused on treatment based on office blood pressure measurements. However, growing evidence shows that pregnant patients benefit from more frequent monitoring. A recent study showed improved pregnancy outcomes for diabetic pregnant patients (n=533) when remote patient monitoring of glucose control was implemented.24 I hypothesize that frequent remote monitoring of blood pressure and real-time antihypertensive medication titration will optimize pregnancy outcomes in a clinically meaningful and cost-effective manner compared to the current standard of care. Therefore, this pilot study, as part of the K12 training support, will evaluate the feasibility of a randomized clinical trial to treat mild chronic hypertension with medication therapy to a blood pressure goal of less than 140/90 mmHg based on remote daily patient monitoring compared to in-office blood pressure readings (Figure 1). For this trial, patients before 20 weeks' gestation will be recruited (N=50) to the remote monitoring arm (n=25) or the in-office arm (n=25). CHAP guidelines will be used to titrate medication use in each arm.

Specific Aim 1: To evaluate whether remote patient blood pressure monitoring during the antepartum period for patients with chronic hypertension will improve composite perinatal outcomes. Hypothesis: In patients with chronic hypertension, tight blood pressure control with remote patient monitoring will improve composite outcomes. Participants in the two trial arms will be compared for the frequency of composite perinatal outcomes (perinatal death, placental abruption, superimposed preeclampsia with severe features, or indicated preterm birth \<35 weeks). Compliance with the assigned study group will also be assessed.

Specific Aim 2: Assess the impact of remote patient monitoring for chronic hypertension during pregnancy on changes in cardiac strain. Hypothesis: Tight blood pressure control using remote patient monitoring will decrease maladaptive cardiac remodeling during late gestation, which will persist into the postpartum period. Cardiac strain will be assessed using speckle-tracking echocardiography at enrollment and 34 to 36 weeks of gestation.

Exploratory Aim: To compare the accuracy of OB/GYN-derived Point of Care Ultrasound (POCUS) cardiac strain assessments and diastolic parameters to the echocardiogram-derived assessment, we will seek to determine if POCUS images obtained by a physician without echocardiogram training will produce reliable results compared to those obtained with an echocardiogram.

Completing this feasibility study and planned training will provide the requisite preliminary data, knowledge, and skills to apply for an R01 grant from NICHD/NHLBI during the second year of the K12. The structured research training and mentoring enabled by the K12 will substantially accelerate my transition to an independently funded physician-scientist committed to improving perinatal clinical outcomes for patients.

1.3 Research Design and Methods A. Research Procedures The pilot study aims to evaluate the feasibility of a randomized clinical trial to treat chronic hypertension with antihypertensive therapy to a blood pressure goal of less than 140/90 mm Hg based on remote patient monitoring compared to in-office blood pressure readings. The primary clinical outcome is a composite perinatal outcome (perinatal death, placental abruption, superimposed preeclampsia with severe features, or indicated preterm birth \<35 weeks). Feasibility outcomes will focus on developing recruitment procedures, determining consent rate, developing and testing approaches to measure outcomes, testing blood pressure regimen, and determining the feasibility of echocardiogram assessments. One hundred patients will be enrolled from Rutgers Robert Wood Johnson University Hospital, New Brunswick, NJ.

Inclusion and exclusion criteria: Patients with a viable pregnancy \<23 weeks of gestation will be screened for chronic hypertension by either identifying those currently receiving treatment for hypertensive disorders or patients with newly diagnosed or untreated chronic hypertension defined as systolic blood pressure \>=140 mm Hg or diastolic blood pressure \>=90 mm Hg prior to 20 weeks gestation. Patients must be 18 years of age or older and speak English or Spanish. They also must be able to sign a consent. Patients will be excluded if they have a known secondary cause of hypertension, known major fetal anomaly, known fetal demise, suspected fetal growth restriction, membrane rupture, planned termination, plan to deliver outside of the RWJ Barnabas Health system, known sensitivity to labetalol or nifedipine or unlikely to follow up in the opinion of the study staff.

Baseline assessment: Standard of care labs will be collected for all patients who have not previously had them drawn, includ

• Cardiac strain [Срок оценки: 36 weeks gestation]
• POCUS [Срок оценки: 36 weeks gestation]