Safety, Feasibility, and Impact of Enalapril on Cardiorespiratory Physiology and Health in Preterm Infants with Systemic Hypertension and Left Ventricular Diastolic Dysfunction

Abstract

Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was started in neonates with systemic hypertension and echocardiography signs of LV diastolic dysfunction. A total of 11 patients were included with birth weight of 785 ± 239 grams and gestational age of 25.3 (24, 26.1) weeks. Blood pressure improvement was noticed within 2 weeks of treatment. Improvement in LV diastolic function indices were observed with a reduction in Isovolumic Relaxation Time (IVRT) from 63.1 ± 7.2 to 50.9 ± 7.4 msec and improvement in the left atrium size indexed to aorta (LA:Ao) from1.73 (1.43, 1.88) to 1.23 (1.07, 1.29). Neonatal systemic hypertension is often underappreciated in ex-preterm infants and may be associated with important maladaptive cardiac changes with long term implications. It is biologically plausible that identifying and treating LV diastolic dysfunction in neonates with systemic hypertension may have a positive modulator effect on cardiovascular health in childhood and beyond.

Keywords: angiotensin-converting enzyme inhibitor; bronchopulmonary dysplasia; cardiac lung disease; enalapril; left ventricular diastolic dysfunction; systemic hypertension.

Figure 1

Time-series trends in the Systolic and Diastolic Arterial pressure before/after enalapril. Individual Systolic Blood Pressure (SBP) (Panel A) and Diastolic Blood Pressure (DBP) (Panel B) trends at three time points. At time of diagnostic echocardiogram (ECHO), and with two follow up ECHOs. ECHO 1: in average 2 weeks after starting enalapril therapy and, ECHO 2: prior to discharge. Each patient is represented in a different color and vignette. 4 patients did not undergo ECHO assessment at 2 weeks after treatment, and only had one follow up ECHO prior to discharge.

Figure 2

Select echocardiography indices of left heart diastolic function before/after enalapril treatment. Individual changes to Isoloumic Relaxation Time (IVRT) (Panel A) and Left Atrium indexed to Aortic size (LA:Ao) (Panel B) after treatment with enalapril, baseline shown at time of diagnostic ECHO vs Follow up ECHO prior to discharge. Each patient is represented in a different color and vignette.