NO donors on top of anti-hypertensive therapy reduces complications in chronic hypertensive pregnancies with hypodynamic circulation

Abstract

Objectives: Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients. We further evaluated if the possible hemodynamic modification induced by NO donors and increased oral fluid intake might be associated to a reduction of the severity and rate of complications vs. patients on antihypertensive standard treatment.

Study design: This was a case-control study of 321 chronic hypertensive patients with a hypodynamic circulation at the echocardiographic evaluation at 24 weeks' gestation. We included 160 controls (standard antihypertensive therapy) and 161 cases (standard therapy + NO donor patches + increased oral fluid intake). Student T test for paired and unpaired data, univariate logistic regression analysis, ROC curve analysis, and Cox Hazards Regression analysis were used as appropriate.

Results: At enrollment the hemodynamic parameters were similar between the two groups. After 3-4 weeks stroke volume (77 ± 19 mL vs. 69 ± 19 mL; p < 0.001), and cardiac output (6.2 ± 1.7 L vs. 5.0 ± 1.6 L; p < 0.001) were higher and total peripheral vascular resistance (1465 ± 469 dyne·s·cm^-5 vs. 1814 ± 524 dyne·s·cm^-5; p < 0.001) was lower in the cases vs controls. Superimposed preeclampsia, preterm delivery before 34 weeks, abruptio placentae, HELLP Syndrome, fetal growth restriction, and perinatal death were more represented in the standard treatment group vs NO treated patients (81% vs 53%; p < 0.001). In particular, the standard treatment group showed 48% fetal growth restriction vs 34% in the NO treated group (p < 0.011). The Cox proportional-hazards regression showed a lower proportion of event-free pregnancies in controls on standard treatment (HR 2.6; 95% CI 2.0-3.5; p < 0.0001), and a prolongation of pregnancies in CH cases complicated by fetal growth restriction taking NO donors (HR 0.29; 95% CI 0.19-0.43; p = 0.0001).

Conclusions: The tailored treatment with NO donors and oral fluids of hypodynamic CH might have positive effects on the reduction or mitigations of adverse outcomes.

Keywords: Fetal growth restriction; Hypodynamic chronic hypertension; Maternal hemodynamics; NO donors; Oral fluid intake; Preeclampsia.