Optimizing PH-Related Pregnancy Outcomes Requires Additional Risk Stratification

Because of ongoing high rates of major adverse cardiovascular events (MACE) and fetal adverse clinical events (FACE) among critically ill pregnant women who have pulmonary hypertension (PH), more refined risk stratification is needed to optimize outcomes among this patient population.

Findings, published in Frontiers in Cardiovascular Medicine, also demonstrate that more effective therapies are needed for this group.

In this multicenter retrospective cohort study, there were 3 groups of pregnant patients, and they were stratified by systolic pulmonary arterial pressure (sPAP): mild PH was 30 to 50 mm Hg (n = 101), moderate PH was 51 to 70 mm Hg (n = 31), and severe PH was over 70 mm Hg (n = 49).

A composite measure of in-hospital death, heart failure, and sustained arrhythmias requiring treatment made up the MACE evaluated; this was the primary outcome. A composite of fetal/neonatal death, prematurity, small birth weight, and fetal distress made up the FACE evaluated; this was the secondary outcome. The median (IQR) participant age was 32 (27-35) years

“Advances in the management of PH and pregnancy have significantly improved the pregnancy outcome of patients with PH,” the study investigators wrote. “However, there are limited data on pregnancy outcomes and risk factors of critically ill PH patients admitted to the intensive care unit [ICU].”

The overall rate of MACE was 32.6% (59/181 patients), and of this group, the most common event was heart failure in 90% (53/59). In-hospital death was the next most common MACE, and this occurred in 22% (13/59), and this was followed by sustained arrhythmias in 11.8% (7/59).

More than one-third of the overall patient population (37%) was in their first pregnancy, and all had been admitted to the ICU between January 1, 2013, and December 31, 2018, at Shandong First Medical University or Binzhou Medical University Hospital from a maternal referral center. Data came from their electronic medical records.

When analyzing outcomes by sPAP stratification, patients in the severe PH cohort had a mortality rate of 22.4% vs 1.51% seen among patients in the mild and moderate groups (P < .001). MACE incidence was also significantly elevated, being almost twice as high, among the pregnant patients with severe PH vs mild and moderate PH: 51.0% vs 25.8% (P = .001).

Patients in the severe PH group were the youngest, at 24 (30-34) years and those with mild PH were the oldest, at 29 (33-37) years. More than half of the patients in each PH group received their PH diagnosis before becoming pregnant: 58.6% (mild PH), 77.4% (moderate PH), and 73.5% (severe PH).

Overall FACE incidence was more than twice the MACE rate, at 66.3% (120/181 patients), and incidence rate differences persisted between those with severe PH and mild/moderate PH, although the study authors deemed the difference nonsignificant: 69.4% vs 65.1%, respectively (P = .724). Within this grouping, the most common FACE were therapeutic abortion in 9.4%, small birthweight in 34.8%, and prematurity in 59.7%.

Multivariate logistic regression analysis of MACE showed independently associated higher mortality risks from several PH disease indicators:

• Complications from left heart disease: 337% greater risk (odds ratio [OR], 4.365; 95% CI, 1.306-14.59)
• Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) level: 5.1% higher risk (OR, 1.051; 95% CI, 1.015-1.088)
• sPAP estimated by echocardiography: 2.5% higher risk (OR, 1.021; 95% CI, 1.003-1.040)

When FACE were further evaluated, also via multivariate logistic regression analysis, eclampsia/preeclampsia had a 571% higher risk (OR, 6.713; 95% CI, 1.806-24.959).

“Pregnancy with PH has a high risk of death. Compared with the maternal mortality rate (18.3/100,000) in China in in 2018, the mortality rate of pregnant patients complicated with PH increased by nearly 400 times in the present study,” the investigators wrote.

The authors also found the following:

• Cesarean section delivery occurred in 96.1%, with 20.4% being emergencies
• General anesthesia was most common in the severe PH group, at 49%
• Patients with severe PH had the highest scores for sequential organ failure assessment and Acute Physiology, Age and Chronic Health Evaluation II
• Patients with severe PH had higher levels of blood lactate and D-dimer
• Most patients with severe PH saw their New York Heart Association disease class decrease by 1 or 2 in their final trimester

“PH patients with left heart disease, increased sPAP estimated by echocardiography, and elevated NT-proBNP are at high risk of cardiac adverse events and should receive closer medical monitoring,” the authors concluded. “If necessary, planned early delivery should be considered to avoid sudden deterioration of cardiac function.”

Reference

Zhang L, Qie G, Yin X, et al. Pregnant outcomes of critically ill pregnant patients with pulmonary hypertension: a multicenter retrospective study. Front Cardiovasc Med. Published online September 7, 2022. doi:10.3389/fcvm.2022.872833