Impaired myocardial energetics and lower cardiac reserve in response to exercise stress in adults born preterm

Abstract

Abstract Background/Introduction Preterm birth (<37 weeks’ gestation) affects 10% of live births globally and associates with an increased risk of heart failure, early cardiovascular-related mortality, and altered cardiac morphology. At rest, left ventricular (LV) ejection fraction (EF) is similar between adults born preterm and term, but right ventricular (RV) EF is lower in preterm-born adults. Exercise stress uncovers LVEF impairment in preterm-born adults but RVEF response to exercise stress has not been studied. The underlying cause of the impaired LVEF reserve and lower RVEF at rest in preterm-born adults remains uncertain and whether altered myocardial energetics contribute to this cardiac dysfunction is currently unknown. Purpose To measure resting myocardial energetics and ventricular function at rest and during exercise stress to determine whether reduced cardiac reserve in preterm-born adults may be explained by impaired myocardial energetics. Methods We conducted a cross-sectional, observational, case-control study of preterm (n=64; mean gestational age =31 weeks) and term-born (n=36) adults aged 34±5 years to compare myocardial energetics and ventricular function. Following maximal cardiopulmonary exercise testing (CPET), participants underwent 31-phosphorus magnetic resonance (MR) spectroscopy (31-P MRS) and cardiovascular MR imaging (CMR) on a 3-Tesla Siemens MR scanner. 31-P MRS was used to measure myocardial phosphocreatine to adenosine triphosphate ratio (PCr/ATP) as a measure of myocardial energetics. We obtained CMR-derived LVEF and RVEF at rest and during 40% peak wattage exercise (determined from CPET) using a MR compatible cardio-step module and steady-state free precession real-time cine imaging. Outcomes were analysed using unpaired Student’s t-tests and presented as mean±standard deviation. Results Age, body mass index, and sex did not differ between groups (p>0.05). PCr/ATP was 1.8±0.4 in preterm-born adults and 2.0±0.4 in term-born adults (p=0.01, Figure 1). Preterm-born adults had a similar LVEF versus term-born adults at rest (60.3±7.6 versus 62.1±4.5; p=0.19) though resting RVEF was lower in preterm-born adults (53.4±6.7 versus 55.9±4.5; p=0.05). LVEF increased by 6.5±5.5% in preterm-born adults and 10.9±6.0% in term-born adults from rest to 40% peak exercise (p<0.001), while RVEF increased by 9.2±6.3% in preterm-born adults versus 12.0±6.3% in term-born adults (p=0.06) (Figure 2). PCr/ATP associated with resting RVEF in preterm-born adults (R²=0.27, p=0.002), but was not associated with resting LVEF or the delta change in LVEF and RVEF with exercise stress. Conclusions Resting myocardial energetics is impaired in adults born preterm relative to term-born adults, with both the LV and RV demonstrating reduced functional reserve when challenged with low to moderate exercise stress. Metabolic modulators may help prevent progression to heart failure in preterm-born adults.Figure 1Figure 2