Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults

Abstract

Background: Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk.

Objectives: The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise.

Methods: We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing.

Results: Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m² vs. 1,669 ± 937 ml/min/m²; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively).

Conclusions: Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231).

Keywords: cardiac function; echocardiography; ejection fraction; heart failure; myocardial reserve; premature; preterm.

Graphical abstract

Central Illustration

Left Ventricular Ejection Fraction With Increasing Exercise Intensity in Preterm-Born Versus Term-Born Young Adults Preterm-born young adults (orange) had a lower ejection fraction (EF) than term-born young adults (blue) at 60% and 80% of peak exercise intensity (71.9 ± 8.7% vs. 78.6 ± 5.4% and 69.8 ± 6.4% vs. 77.1 ± 6.3%, respectively; p < 0.005). In the preterm group, EF at 60% and 80% exercise intensity were both significantly lower than the within-group EF at 40% intensity (3.7% and 5.8% lower, respectively; p < 0.05). This declining EF with increasing exercise intensity was not observed in term-born control subjects. Error bars represent SEM. *Significantly lower EF than that in the term-born group (p < 0.005). †Significantly lower than the within-group EF at 40% (p < 0.05).

Figure 1

Submaximal Exercise Cardiac Output Reserve With Increasing Exercise Intensity in Preterm Versus Term-Born Young Adults Submaximal cardiac output reserve values at 40%, 60%, and 80% exercise intensity were calculated by subtracting resting cardiac index from the cardiac index at each exercise intensity level. Submaximal exercise cardiac output reserve at 40% of peak exercise intensity was 56% lower in the preterm-born group versus term-born control subjects (p = 0.021). Error bars represent SEM. Bold p values are statistically significant (p < 0.05).

Figure 2

Relationship Between Left Ventricular Length and Change in Ejection Fraction When Going From Rest to 60% Exercise Intensity in Preterm-Born Versus Term-Born Young Adults (A) In preterm-born adults, greater left ventricular (LV) length was strongly correlated with increasing ejection fraction (EF) when going from rest to 60% exercise intensity (p < 0.01). (B) In term-born adults, LV length was not correlated with a change in EF when going from rest to 60% exercise intensity (p = 0.46).