A total of 20 preterm infants were enrolled. The median gestational age at birth was 28.0 weeks [IQR 26.8–29.4], and the median birth weight was 930 g [IQR 810–1080]. Six infants (30%) were classified as small for gestational age (SGA). The cohort included 11 male (55%) and 9 female (45%) infants. The median Apgar scores were 5 [IQR 4–6] at 1 min and 7 [IQR 6–8] at 5 min. Most infants (70%) were of Hispanic ethnicity. Delivery was by cesarean section in 15 of 20 infants (75%). Antenatal corticosteroids were administered to 17 mothers (85%). At the time of the initial echocardiogram, 3 infants (15%) were receiving invasive mechanical ventilation, while the remaining 17 (85%) were on noninvasive respiratory support. By day 7, 85% of the cohort remained on noninvasive support. Clinical morbidities included treated hypotension in 3 infants (15%) and intraventricular hemorrhage in 7 infants (35%), of which two cases (10%) had grade III or IV intraventricular hemorrhage. Notably, two infants received Dopamine (2.5–10 µg/kg/min) during the 48 h echocardiogram, and a third infant was on Dopamine infusion (5–10 µg/kg/min) at the day 7 echo timepoint. Additional demographic and perinatal characteristics are summarized in Table 1.

Serial echocardiographic assessments demonstrated evolving diastolic function during the first week of life (Table 2; Fig. 1). At 24 h of life, the mitral E/A ratio was < 1.0 in most infants (median 0.90 [IQR 0.82–0.98]). The ratio decreased slightly at 48 h (median 0.86 [IQR 0.79–0.93]), followed by a modest increase at 72 h (median 0.89 [IQR 0.82–0.96]) and at day 7 (0.92 [IQR 0.85–0.99]). These changes were not statistically significant (p = 0.09, Friedman test). E and A wave fusion precluded discrete measurement in 3 infants (15%) during early time points.

Longitudinal changes in diastolic function and left atrial indices in preterm infants during the first week of life Mitral inflow E/A ratio (a), lateral mitral annular e′ velocity (b), mitral E/e′ ratio (c), and indexed left atrial volume (d) are shown from 24 h to day 7. Median values and interquartile ranges are depicted. N = 20 infants

The average mitral annular e′ velocity, calculated as the mean of septal and lateral e′, increased from 3.3 cm/s [IQR 2.9–3.6] at 24 h to 3.9 cm/s [IQR 3.5–4.3] at day 7 (p = 0.004).

Mitral E/e′ ratio decreased over time, from 16.4 [IQR 14.2–18.3] to 13.1 [IQR 11.3–15.1] by day 7 (p < 0.01). The most pronounced reduction occurred between 24 and 48 h. In three infants who required invasive mechanical ventilation during the first week, E/e′ remained elevated (> 16) at day 7 despite overall improvement in the cohort.

Indexed left atrial (LA) volume increased from 0.88 mL/kg [IQR 0.74–1.00] at 24 h to 1.07 mL/kg [IQR 0.96–1.21] at day 7 (p = 0.12). When stratified by gestational age, infants < 27 weeks (n = 9) showed a more pronounced increase (median change + 0.29 mL/kg, IQR 0.18–0.41) compared to those ≥ 27 weeks (+ 0.12 mL/kg, IQR 0.05–0.19). Atrial filling fraction followed a similar trend, with a median of 0.55 [IQR 0.50–0.62] at 24 h and 0.50 [IQR 0.44–0.56] at day 7.

Right-sided parameters were tracked in all infants. Tricuspid E/A ratio increased from 0.78 [IQR 0.69–0.86] to 0.89 [IQR 0.81–0.97] (p = 0.02). Tricuspid e′ increased from 4.6 cm/s [IQR 4.1–5.1] to 5.1 cm/s [IQR 4.6–5.7] (p = 0.03), though values were highly variable between infants (range at day 7: 3.7–6.3 cm/s).

Sensitivity analysis excluding timepoints with concurrent inotropic support (n = 3 timepoints from 3 infants) yielded slightly lower mitral E/e′ values at 48 h (12.8 [IQR 11.0–14.6] vs. 13.7 [11.8–15.5]) and day 7 (12.6 [IQR 10.9–14.0] vs. 13.1 [11.3–15.1]). The average e′ velocity also demonstrated a more pronounced increase in the sensitivity cohort, from 3.3 to 3.9 cm/s (p = 0.005). Indexed LA volumes remained within a comparable range, although slightly lower at 48 h (0.97 [0.85–1.07] mL/kg). Overall trends remained directionally consistent (See Supplemental Table S2 for details of sensitivity analysis).

At 48 h of life, 7 infants (35%) met criteria for a hsPDA, and 6 infants (30%) continued to meet criteria at day 7.

By day 7, infants with hsPDA demonstrated higher mitral E/A ratios (1.08 [IQR 1.01–1.14]) compared to those without PDA (0.95 [IQR 0.89–1.00], p = 0.04). Median mitral E/e′ was significantly higher in the hsPDA group (9.1 [IQR 8.4–10.0]) than in non-hsPDA infants (6.4 [5.7–7.1], p < 0.01), though overlap between groups was noted. Indexed LA volume was also larger in the hsPDA group (1.14 [IQR 1.05–1.22] mL/kg vs. 0.91 [0.84–0.98] mL/kg, p < 0.01), with 3 infants exceeding 1.3 mL/kg at day 7.

Atrial filling fraction was modestly higher in the hsPDA group (median 0.58 [0.51–0.63]). Lateral e′ values trended lower (3.2 [2.9–3.6] vs. 3.7 [3.3–4.0], p = 0.06), though distributions overlapped. Notably, none of the non-hsPDA infants had an E/e′ > 10 or LA volume index > 1.2 mL/kg.

At day 7, four of the hsPDA infants (67%) were receiving pharmacologic treatment with acetaminophen, while two had not yet initiated or completed therapy. In the treated infants, LA volume and E/e′ values remained elevated but showed a downward trend compared to untreated hsPDA infants.

Sensitivity analysis excluding echocardiographic timepoints during inotropic exposure (n = 3 infants) revealed consistent trends. Among infants with hsPDA, median E/e′ decreased slightly to 8.6 [IQR 7.9–9.7], and indexed LA volume decreased to 1.09 [IQR 1.01–1.19] mL/kg. Although absolute values were lower, both measures remained significantly higher compared to non-hsPDA infants (E/e′: 6.3 [5.7–7.1], LA volume: 0.91 [0.84–0.98] mL/kg, both p < 0.01). The mitral E/A ratio and atrial filling fraction were unchanged in sensitivity analysis.

Left ventricular cardiac output increased from 191 [178–210] at 24 h of age to 281 [260–306] mL/kg/min at 48 h of age. By day 7, LVO plateaued at a median of 278 mL/kg/min [IQR 252–310]. Right ventricular output increased from 205 [IQR 190–226] at 24 h to 265 [IQR 240–288] mL/kg/min by 48 h, remaining stable at a median of 263 mL/kg/min [IQR 235–290] through day 7.

Infants with hsPDA demonstrated higher peak LVO values at 48 h.

(301 [IQR 276–326]) compared to those without hsPDA (265 [IQR 234–296] ml/kg/min, p = 0.02).

Sensitivity analysis excluding echocardiograms performed during inotropic support demonstrated similar trends in cardiac output. Median LVO at 48 h was 289 [IQR 258–305] mL/kg/min and RV output was 262 [IQR 235–284] mL/kg/min, closely mirroring the original values.

A total of 17 infants (85%) demonstrated left-to-right shunting across a patent foramen ovale (PFO) during the first week of life. Of these, 6 infants (35%) had a PFO diameter ≥ 2.5 mm. Stratified analysis by hsPDA status revealed that among infants without hsPDA during the first week of life (n = 13), those with a larger PFO (≥ 2.5 mm, n = 4) had lower indexed left atrial (LA) volumes (0.89 [IQR 0.83–0.96] mL/kg) and E/e′ ratios (6.1 [5.4–6.7]) compared to those with a smaller PFO (< 2.5 mm, n = 9; LA volume: 1.03 [0.94–1.14] mL/kg; E/e′: 7.0 [6.2–8.1]). Among infants with hsPDA during the first week of life (n = 7), no consistent association between PFO size and diastolic parameters was observed. No significant differences were observed in mitral E/A ratio or e′ velocities based on PFO size.