Exercise-induced irregular right heart flow dynamics in adolescents and young adults born preterm

Abstract

Background Preterm birth has been linked to an elevated risk of heart failure and cardiopulmonary disease later in life. With improved neonatal care and survival, most infants born preterm are now reaching adulthood. In this study, we used 4D flow cardiovascular magnetic resonance (CMR) coupled with an exercise challenge to assess the impact of preterm birth on right heart flow dynamics in otherwise healthy adolescents and young adults who were born preterm. Methods Eleven young adults and 17 adolescents born preterm (< 32 weeks of gestation and < 1500 g birth weight) were compared to 11 young adult and 18 adolescent age-matched controls born at term. Stroke volume, cardiac output, and flow in the main pulmonary artery were quantified with 4D flow CMR. Kinetic energy and vorticity were measured in the right ventricle. All parameters were measured at rest and during exercise at a power corresponding to 70% VO2max for each subject. Multivariate linear regression was used to perform age-adjusted term-preterm comparisons. Results With exercise, stroke volume increased 10 ± 21% in term controls and decreased 4 ± 18% in preterm born subjects (p = 0.007). This resulted in significantly reduced capacity to increase cardiac output in response to exercise stress for the preterm group (58 ± 26% increase in controls, 36 ± 27% increase in preterm, p = 0.004). Elevated kinetic energy (KEterm = 71 ± 22 nJ, KEpreterm = 87 ± 38 nJ, p = 0.03) and vorticity (ωterm = 79 ± 16 s−1, ωpreterm = 94 ± 32 s−1, p = 0.01) during diastole in the right ventricle (RV) suggested altered RV flow dynamics in the preterm subjects. Streamline visualizations showed altered structure to the diastolic filling vortices in those born preterm. Conclusions For the participants examined here, preterm birth appeared to result in altered right-heart flow dynamics as early as adolescence, especially during diastole. Future studies should evaluate whether the altered dynamics identified here evolves into cardiopulmonary disease later in life. Trial registration None

Differing Impact of Preterm Birth on the Right and Left Atria in Adulthood

“…Both of these mechanisms seem to enhance atrial stroke volume and thus might compensate for the reduced RA volumes, although indexed RV stroke volume remained lower in preterm‐born compared with term‐born adults. These findings align with previous findings of altered RV flow patterns in preterm‐born adults during exercise, 69 as changes in RA deformation might contribute to alterations in RV flow during diastole. Additionally, the exaggerated RA booster function also corresponds to previous findings suggesting possible compensatory mechanisms for volumetric limitations in the RV of preterm‐born adults.…”

Preterm‐born individuals: a vulnerable population at risk of cardiovascular morbidity and mortality during thermal extremes?

“…This was matched by a significant ∼50% reduction in cardiac reserve from 40% of exercise capacity (Huckstep et al., 2018 ). Such findings are supported by evidence of increased aortic stiffness, and associated BP elevations, as well as attenuated stroke volume and cardiac output during exercise in preterm born adults (Barnard et al., 2020 ; Macdonald et al., 2021 ). In addition to poor performance, recovery from exercise stress may also be affected, with Haraldsdottir et al.…”

“…Overt cardiovascular dysfunction can be observed in preterm‐born adolescents and young adults during exercise stress (Table 1 ). This includes progressive cardiac impairment, increased pulsatility of blood flow and elevated BP during graded exercise (Barnard et al., 2020 ; Huckstep et al., 2018 ; Macdonald et al., 2021 ). Similar limitations are observed in the progressive deterioration associated with ‘traditional’ CVD.…”

“…Elderly hearts exhibit attenuated changes in cardiac output and elevated cardiac strain during heat stress (Gravel et al., 2021 ). Similarly, impaired cardiac output and ventricular function are present in preterm‐born adults under exercise stress (Huckstep et al., 2018 ; Macdonald et al., 2021 ). Like those with CVD, preterm populations exhibit persistent systemic inflammation and autonomic dysregulation.…”

Intrauterine inflammation exacerbates maladaptive remodeling of the immature myocardium after preterm birth in lambs

“…Given the limited replicative capacity of cardiomyocytes postnatally, the reduced endowment of LV + S cardiomyocytes following preterm birth may adversely impact lifelong functional reserve and the adaptive (structural and functional) capabilities of the myocardium for physiological hypertrophy in those individuals born preterm. Recent studies highlight impaired LV 57 , 58 and RV 59 , 60 function of preterm-born young adolescents and adults when physiologically challenged with exercise, which is suggestive of reduced cardiac functional reserve. Similarly, a number of clinical and experimental reports highlight a unique cardiac phenotype in those born preterm compared to term counterparts, including altered cardiac function, evidence of myocardial remodeling, and changes to cardiomyocyte maturation (including nuclearity, size, and ploidy).…”