Exercise intolerance in adolescents born preterm associated with left ventricular diastolic dysfunction

Abstract

IntroductionPreterm birth disrupts the development of vital organ systems, and places significant challenges on these systems to function in an underdeveloped state. Physiological challenges have been well documented in the preterm infant, and recent evidence suggests that young adults born preterm have higher incidence of hypertension, cardiac dysfunction, and exercise intolerance. However, it is unclear whether adolescent children who received modern neonatal care, including surfactant therapy and lower mechanical ventilation pressures, express these same impairments. Our study sought to determine exercise capacity in adolescents born preterm, as well as resting blood pressure (BP), stroke volume (SV) during exercise, and left ventricular (LV) function using a cardiac MRI.MethodsAdolescent children born preterm in 2003 and 2004 weighing <1500g with an average gestational age of 28 weeks, and healthy age‐matched controls with an average gestational age of 40 weeks were studied. Participants filled out a self‐reported physical activity questionnaire (PAQ) and underwent progressive maximal exercise testing on the upright cycle ergometer, where maximal aerobic capacity (VO2max), maximal power (Pmax), and time to exhaustion (Tmax) were determined. SV throughout exercise was determined using thoracic bioimpedance (PhysioFlow). Average resting BP was recorded during a 10‐minute supine rest, and resting cardiac structure and function measurements were acquired by cardiovascular magnetic resonance by a 3‐T GE scanner. Statistics were performed using Mann‐Whitney tests, and significance was determined as p<0.05. Results are reported as mean±SD.ResultsPreterm adolescents had lower absolute VO2max than controls (2.1±0.5 vs 2.5±0.5 L/min, respectively, p=0.01), lower Pmax, (124±27 watts vs 151±29, p<0.01), lower Tmax, (8.3±2.6 minutes vs 10.4±2.1, p<0.01), with no difference in PAQ scores. Mean BP was higher in preterms than controls (82.2±3.7 vs 76.6±4.0 mmHg, p<0.01), and sex‐, age‐ and height‐adjusted median z‐scores for systolic BP (SBP) and diastolic BP (DBP) were significantly higher in preterms than controls (SBP 0.60±0.57 vs −0.09±0.38, p<0.01), (DBP 0.22±0.46 vs −0.42±0.51, p<0.01). At rest, preterms had lower end diastolic volume (EDVi) (72.9±9.5 vs 84.2±7.2 ml/m2, p=0.02), with a higher LV ejection fraction (EF; 64.1±3.5 vs 58.1±5.5%, p=0.02). The change in SV from rest to maximal exercise was significantly lower in preterms (ΔSV; 4.8±12.7 vs 26.2±18.7 ml, p<0.01).DiscussionWhile the underlying mechanisms of exercise impairment in our population are unclear, we found that preterm adolescents have higher resting BP, lower EDVi, elevated EF, and a blunted SV response to maximal exercise. A lower EDVi suggests diastolic dysfunction, and combined with an elevated EF at rest suggests a hyperdynamic heart. Taken together, our data suggest that there may be a cardiac function limitation in conjunction with cardiovascular autonomic dysfunction causing exercise intolerance in this young population. Our findings, together with blunted stroke volume reserve during exercise, resemble those seen in early stage heart failure with preserved EF, and suggest further study in this population.Support or Funding InformationNIH‐NHLBI R01–HL115061This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.