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Study Objectives: Determine whether preterm-born adolescents and adults have sleep-disordered breathing (SDB), as documented by abnormal overnight oximetry., Methods: This single-center cross-sectional study prospectively enrolled adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 grams birth weight) or full term to complete a study visit, STOP-Bang questionnaire, and overnight oximetry. Oxygen desaturation index (ODI) was compared in preterm versus term with Poisson regression models. Subgroup analyses in preterm participants evaluated associations of neonatal risk factors with ODI., Results: Ninety-six preterm and 44 term participants completed study procedures. Preterm participants more often reported snoring (25% vs 9%; p=0.03) and excessive fatigue (62% vs 40%; p=0.02), and had higher body mass index, leading to higher STOP-Bang scores (2±1 vs 1±1; p<0.001). Preterm participants had 40% higher ODI (incidence rate ratio (IRR): 1.40; 95% CI [1.07,1.83]; p=0.02). However, after adjusting for classic risk factors for SDB including age and STOP-Bang score in a multivariable model, history of preterm birth did not predict additive risk for SDB. Among neonatal factors, a patent ductus arteriosus was associated with a higher ODI (IRR 1.99; 95% CI [1.37,2.91]; p<0.001)., Conclusions: Preterm-born adolescents and adults in this study have higher rates of snoring, daytime fatigue, and nocturnal desaturations compared to those term-born. However, the risk of elevated ODI is best attributed to obesity in this cohort and not the history of prematurity. Additionally, a history of a patent ductus arteriosus increased risk for SDB., (© 2024 American Academy of Sleep Medicine.)

Background: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise., Methods and Results: Adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g birth weight) were recruited from the Parkland Health Neonatal Intensive Care Unit Registry. Full-term participants were recruited from the local area. Study procedures included anthropometrics and vitals, handgrip testing, and echocardiography performed at rest and during isometric handgrip exercise. Data were reported as mean±SD. The study enrolled 107 preterm and 48 term participants. Preterm participants (gestational age: 29.5±2.5 weeks) were shorter with higher body mass index ( P <0.001) compared with term participants. Preterm participants exhibited smaller LV end-diastolic volume index (50.8±10.1 versus 56.9±10.0 mL/m 2 , P <0.001), LV stroke volume index (29.6±6.0 versus 34.1±6.5 mL/m 2 , P <0.001), and LV mass index (67.2±13.1 versus 73.3±14.2 g/m 2 , P =0.002) compared with term individuals. Preterm participants also had subclinical reductions in LV peak systolic tissue velocity and peak early diastolic tissue velocity lateral at rest. Isometric handgrip exercise promoted a reduction in diastolic function and an increase in hemodynamic measures, but changes during isometric handgrip exercise were similar between groups., Conclusions: Adolescents and adults born preterm exhibit overall normal cardiac function despite smaller cardiac volumes and mass compared with individuals born full term. Effects are most pronounced at the lowest gestational ages.

Competing Interests: Disclosures None.

Objectives: 4D flow MRI allows for a comprehensive assessment of intracardiac blood flow, useful for assessing cardiovascular diseases, but post-processing requires time-consuming ventricular segmentation throughout the cardiac cycle and is prone to subjective errors. Here, we evaluate the use of automatic left and right ventricular (LV and RV) segmentation based on deep learning (DL) network that operates on short-axis cine bSSFP images., Methods: A previously published DL network was fine-tuned via retraining on a local database of 106 subjects scanned at our institution. In 26 test subjects, the ventricles were segmented automatically by the network and manually by 3 human observers on bSSFP MRI. The bSSFP images were then registered to the corresponding 4D flow images to apply the segmentation to 4D flow velocity data. Dice coefficients and the relative deviation between measurements (automatic vs. manual and interobserver manual) of various hemodynamic parameters were assessed., Results: The automated segmentation resulted in similar Dice scores (LV: 0.92, RV: 0.86) and lower relative deviations from manual segmentation in left ventricular (LV) average kinetic energy (KE) (8%) and RV KE (15%) than the Dice scores (LV: 0.91, RV: 0.87) and relative deviations between manual segmentation observers (LV KE: 11%, p = 0.01; RV KE: 19%, p = 0.03)., Conclusions: The automated post-processing method using deep learning resulted in hemodynamic measurements that differ from a manual observer's measurements equally or less than the variation between manual observers. This approach can be used to decrease post-processing time on intraventricular 4D flow data and mitigate interobserver variability., Key Points: • Our proposed method allows for fully automated post-processing of intraventricular 4D flow MRI data. • Our method resulted in hemodynamic measurements that matched those derived from manual segmentation equally as well as interobserver variability. • Our method can be used to greatly accelerate intraventricular 4D flow post-processing and improve interobserver repeatability., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: To measure native T1 values, a marker of diffuse fibrosis, by using cardiac MRI (CMR) in young adults born prematurely., Materials and Methods: This secondary analysis of a prospective cohort study included young adults born moderately to extremely preterm and age-matched, term-born participants. CMR was performed with a 3.0-T imager that included cine imaging for the quantification of left ventricular (LV) and right ventricular (RV) volumes and function and native saturation recovery T1 mapping for the assessment of diffuse myocardial fibrosis. Values between preterm and term were compared by using the Student t test. Associations between T1 values and other variables were analyzed by using linear regression and multivariate regression., Results: Of the 50 young-adult participants, 32 were born preterm (mean age, 25.8 years ± 4.2 [SD]; 23 women) and 18 were born at term (mean age, 26.2 years ± 5.4; 10 women). Native T1 values were significantly higher in participants born preterm than in participants born at term (1477 msec ± 77 vs 1423 msec ± 71, respectively; unadjusted P = .0019). Native T1 values appeared to be positively associated with indexed LV end-diastolic and end-systolic volumes (β = 2.1, standard error = 0.7 and β = 3.8, standard error = 1.2, respectively), the RV end-diastolic volume index (β = 1.3, standard error = 0.6), and the LV mass index (β = 2.5, standard error = 0.9). Higher T1 values may be associated with reduced cardiac systolic strain measures and diastolic strain measures. Five-minute Apgar scores were inversely associated with native T1 values., Conclusion: Young adults born moderately to extremely preterm exhibited significantly higher native T1 values than age-matched, term-born young adults. Keywords: MRI, Cardiac, Heart, Left Ventricle, CardiomyopathiesClinical trial registration no. NCT03245723Published under a CC BY 4.0 license Supplemental material is available for this article., Competing Interests: Disclosures of conflicts of interest: C.J.F. Associate editor of Radiology: Cardiothoracic Imaging. G.P.B. NIAID T32AI007635. P.A.C. No relevant relationships. A.T.B. No relevant relationships. N.C.C. No relevant relationships. M.W.E. NIH grants 1R01 HL086897 and 1R01 HL38149. O.W. Board Advisory Committee member for Society for Magnetic Resonance Angiography; The University of Wisconsin-Madison receives research support from GE Healthcare. K.N.G. Grant funding from NIH., (© 2022 by the Radiological Society of North America, Inc.)

Competing Interests: The authors declare that there are no conflict of interests.

Background: Premature birth affects roughly 10% of live births and is associated with long-term increased risk for multiple comorbidities. Although many comorbidities are associated with increased oxidative stress, the potential late impact of extreme premature birth on mitochondrial function has not previously been assessed. We hypothesized that mitochondrial function would be impaired in adult survivors of premature birth., Methods: Mitochondrial function in peripheral blood mononuclear cells from young adults born moderately to extremely preterm was measured using a Seahorse XF Analyzer at baseline and in response to acute oxidative stress, and compared to age-matched term-born adults. Adult pulmonary function was also obtained., Results: Young adults born preterm (average gestational age 29 weeks) had increased mitochondrial oxygen consumption at baseline, particularly with respect to basal and non-ATP-linked respiration. Maximal and spare capacities were also higher, even in response to acute oxidative stress. Lung function was lower in adults born preterm, and the degree of airflow obstruction correlated only modestly with mitochondrial function., Conclusions: In conclusion, adults born preterm have higher basal and non-ATP-linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm., Impact: Adults born preterm have higher maximal but also higher basal and non-ATP-linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm. Prior studies demonstrate a link between perinatal mitochondrial function and risk for development of bronchopulmonary dysplasia. Here, maximal mitochondrial respiration correlates modestly with adult lung function. Peripheral blood mononuclear cell mitochondrial function may be a biomarker of both early lung function and late cardiometabolic risk after preterm birth., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The development, growth, and function of the cardiac, pulmonary, and vascular systems are closely intertwined during both fetal and postnatal life. In utero, placental, environmental, and genetic insults may contribute to abnormal pulmonary alveolarization and vascularization that increase susceptibility to the development of bronchopulmonary dysplasia (BPD) in preterm infants. However, the shared milieu of stressors may also contribute to abnormal cardiac or vascular development in the fetus and neonate, leading to the potential for cardiovascular dysfunction. Further, cardiac or pulmonary maladaptation can potentiate dysfunction in the other organ, amplify the risk for BPD in the neonate, and increase the trajectory for overall neonatal morbidity. Beyond infancy, there is an increased risk for systemic and pulmonary vascular disease including hypertension, as well as potential cardiac dysfunction, particularly within the right ventricle. This review will focus on the cardiovascular antecedents of BPD in the fetus, cardiovascular consequences of preterm birth in the neonate including associations with BPD, and cardiovascular impact of prematurity and BPD throughout the lifespan., (© 2021 Wiley Periodicals LLC.)

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% VO 2max 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 (KE term  = 71 ± 22 nJ, KE preterm  = 87 ± 38 nJ, p = 0.03) and vorticity (ω term  = 79 ± 16 s -1 , ω preterm  = 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., (© 2021. The Author(s).)

Background: Premature birth is associated with lower levels of cardiorespiratory fitness (CRF) but the underlying mechanisms responsible remain unclear. This study assessed whether differences in cardiac morphology or function mediate differences in CRF among adolescents and young adults born preterm., Methods: Adolescents and young adults born moderately to extremely premature (gestational age ≤ 32 weeks or birth weight < 1500 g) and age-matched term born participants underwent resting cardiac MRI and maximal exercise testing. Mediation analysis assessed whether individual cardiovascular variables accounted for a significant proportion of the difference in maximal aerobic capacity between groups., Results: Individuals born preterm had lower VO2max than those born term (41.7 ± 8.6 v 47.5 ± 8.7, p < 0.01). Several variables differed between term and preterm born subjects, including systolic and diastolic blood pressure, mean pulmonary artery pressure, indexed left ventricular end-diastolic volume (LVEDVi), right ventricular end-diastolic volume (RVEDVi), LV mass (LVMi), LV stroke volume index (LVSVi), and LV strain (p < 0.05 for all). Of these variables, LVEDVi, RVEDVi, LVSVi, LVMi, and LV longitudinal strain were significantly related to VO2max (p < 0.05 for all). Significant portions of the difference in VO2max between term and preterm born subjects were mediated by LVEDVi (74.3%, p = 0.010), RVEDVi (50.6%, p = 0.016), and LVMi (43.0%, p = 0.036)., Conclusions: Lower levels of CRF in adolescents and young adults born preterm are mediated by differences in LVEDVi, RVEDVi, and LVMi. This may represent greater risk for long-term cardiac morbidity and mortality in preterm born individuals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To use four-dimensional (4D) flow MRI to measure intraventricular flow in young adults who were born prematurely to investigate mechanisms that may account for increased heart failure risk in this population., Materials and Methods: In this secondary analysis of a prospective study, a total of 56 young adults participated in an observational cardiac 4D flow MRI study from 2016 to 2020. There were 35 participants who had been born moderately to extremely prematurely (birth weight <1500 g or gestational age ≤32 weeks; 23 women; mean age, 26 years ± 4) and 21 term-born participants (11 women; mean age, 25 years ± 3). Participants underwent cardiac MRI, including cine cardiac structure and function assessment, as well as 4D flow MRI. In each ventricle, normalized kinetic energy (KE/end diastolic volume) and flow through the atrioventricular valve were computed and compared between term-born and preterm participants at systolic and diastolic (early diastolic filling rate [E wave] and late diastolic filling [atrial contraction] rate [A wave]) time points by using Wilcoxon rank-sum tests., Results: Preterm-born participants had lower right ventricular (RV) E wave/A wave (E/A) KE ratios (2.4 ± 1.7 vs 3.5 ± 1.4; P <.01) and lower E/A peak filling rate ratios (computed from RV volume-time curves; 2.3 ± 1.3 vs 3.5 ± 2.5; P = .03). Additionally, viscous energy dissipation was increased during systole (5.7 µW/mL ± 3.0 vs 4.2 µW/mL ± 1.6; P = .03), increased during late diastole (3.9 µW/mL ± 4.0 vs 2.2 µW/mL ± 1.6; P = .03), and summed over the cardiac cycle (2.4 µJ/mL ± 1.0 vs 1.9 µJ/mL ± 0.6; P = .02) in preterm relative to term participants., Conclusion: These results suggest that RV diastolic filling is altered in young adults who were born moderately to severely prematurely. Supplemental material is available for this article. Keywords: Adults, Cardiac, Comparative Studies, MR-Imaging, Right Ventricle © RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: P.A.C. disclosed no relevant relationships. G.P.B. disclosed no relevant relationships. J.A.M. disclosed no relevant relationships. C.J.F. Activities related to the present article: associate editor of Radiology: Cardiothoracic Imaging (not involved in handling of the article). Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. M.W.E. disclosed no relevant relationships. K.N.G. disclosed no relevant relationships. O.W. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author’s institution has a research support agreement with GE Healthcare, not related to this project in particular. Other relationships: disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Extreme preterm birth conveys an elevated risk of heart failure by young adulthood. Smaller biventricular chamber size, diastolic dysfunction, and pulmonary hypertension may contribute to reduced ventricular-vascular coupling. However, how hemodynamic manipulations may affect right ventricular (RV) function and coupling remains unknown. As a pilot study, 4D flow MRI was used to assess the effect of afterload reduction and heart rate reduction on cardiac hemodynamics and function. Young adults born premature were administered sildenafil (a pulmonary vasodilator) and metoprolol (a β blocker) on separate days, and MRI with 4D flow completed before and after each drug administration. Endpoints include cardiac index (CI), direct flow fractions, and ventricular kinetic energy including E / A wave kinetic energy ratio. Sildenafil resulted in a median CI increase of 0.24 L/min/m 2 ( P = 0.02), mediated through both an increase in heart rate (HR) and stroke volume. Although RV ejection fraction improved only modestly, there was a significant increase (4% of end diastolic volume) in RV direct flow fraction ( P = 0.04), consistent with hemodynamic improvement. Metoprolol administration resulted in a 5-beats/min median decrease in HR ( P = 0.01), a 0.37 L/min/m 2 median decrease in CI ( P = 0.04), and a reduction in time-averaged kinetic energy (KE) in both ventricles ( P < 0.01), despite increased RV diastolic E / A KE ratio ( P = 0.04). Despite reduced right atrial workload, metoprolol significantly depressed overall cardiac systolic function. Sildenafil, however, increased CI and improved RV function, as quantified by the direct flow fraction. The preterm heart appears dependent on HR but sensitive to RV afterload manipulations. NEW & NOTEWORTHY We assessed the effect of right ventricular afterload reduction with sildenafil and heart rate reduction with metoprolol on cardiac hemodynamics and function in young adults born premature using 4D flow MRI. Metoprolol depressed cardiac function, whereas sildenafil improved cardiac function including right ventricular direct flow fraction by 4D flow, consistent with hemodynamic improvement. This suggests that the preterm heart is dependent on heart rate and sensitive to right ventricular afterload changes.

Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET-MRI) in young adults born term and preterm during normoxic (N = 28 preterm; 18 term) and hypoxic exposure (12% O 2 ; N = 26 preterm; 17 term) to measure the myocardial metabolic rate of glucose (MMRglc) in young adults born term (N = 18) and preterm (N = 32), hypothesizing that young adults born preterm would have higher rates of MMRglc under normoxic conditions and a reduced ability to augment glucose metabolism under hypoxic conditions. MMRglc was calculated from the myocardial and blood pool time-activity curves by fitting the measured activities to the 3-compartment model of FDG kinetics. MMRglc was similar at rest between term and preterm subjects, and decreased during hypoxia exposure in both groups ( p = 0.02 for MMRglc hypoxia effect). There were no differences observed between groups in the metabolic response to hypoxia, either globally (serum glucose and lactate measures) or within the myocardium. Thus, we did not find evidence of altered myocardial metabolism in the otherwise healthy preterm-born adult. However, whether subtle changes in myocardial metabolism may preceed or predict heart failure in this population remains to be determined.

Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g, N = 32) and born at term ( N = 18) underwent cardiac magnetic resonance imaging under normoxic (21% O 2 ) and hypoxic (12% O 2 ) conditions to assess cardiovascular function. In normoxia, cardiac function parameters were similar between groups. During hypoxia, the right ventricular (RV) contractile response was significantly greater in participants born premature, demonstrated by greater increases in RV ejection fraction (EF) ( p = 0.002), ventricular-vascular coupling (VVC) ( p = 0.004), and strain ( p < 0.0001) measures compared to term-born participants, respectively. Left ventricular contractile reserve was similar to term-born participants. Adults born preterm exhibit an exaggerated contractile response to acute hypoxia, particularly in the RV. This suggests that adults born preterm may have contractile reserve, despite the lack of volume reserve identified in previous exercise studies. However, this exaggerated and hyper-adapted response may also increase their risk for late RV failure.

Background: Portopulmonary hypertension is present in an estimated 5.3% to 8.5% of liver transplant candidates. Untreated, 5-year survival is estimated between 14% and 28%. Moderate-severe disease is a contraindication to liver transplant due to the high perioperative mortality, but patients optimized with pulmonary vasodilator therapy can become eligible for transplant. There is minimal data regarding posttransplant outcomes and ability to discontinue pulmonary vasodilator therapy posttransplant., Methods: We performed a single-center retrospective analysis to evaluate long-term outcomes of patients with moderate-severe portopulmonary hypertension who were optimized with pulmonary vasodilator therapy, became eligible for liver transplant, and subsequently underwent transplant. We identified 24 patients optimized with pulmonary vasodilator therapy who underwent subsequent liver transplantation and 25 patients who were treated with pulmonary vasodilator therapy alone., Results: In the transplanted cohort, 1-year survival from portopulmonary hypertension diagnosis date: 95.8%, 3-year survival: 90.9%, and 5-year survival: 90.9%. Posttransplant; 1-, 3-, and 5-year survival was 86.9%. Among transplanted patients, 41.6% (10/24) were optimized with nonparenteral therapy. Following transplantation, 100% (14/14) of the surviving patients were able to discontinue parenteral therapy; median time: 7.2 months (interquartile range: 5.1-8.9 mo), while 61.9% (13/21) were able to discontinue pulmonary vasodilator therapy altogether; median time: 13.9 months (interquartile range: 5.1-17.6 mo)., Conclusions: Patients who are optimized with pulmonary vasodilator therapy before liver transplant can have excellent long-term outcomes posttransplant. Oral pulmonary vasodilator therapy can be effective treatment to qualify a patient for transplant, and the majority are able to wean from pulmonary vasodilator therapy entirely posttransplant., Competing Interests: The authors declare no funding or conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Although women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Estrogen receptor-α (ERα) has been identified as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains poorly understood. We hypothesized that loss of functional ERα removes female protection from adverse remodeling and is permissive for the development of a maladapted RV phenotype. Male and female rats with a loss-of-function mutation in ERα (ERαMut) and wild-type (WT) littermates underwent RV pressure overload by pulmonary artery banding (PAB). At 10 wk post-PAB, WT and ERαMut demonstrated RV hypertrophy. Analysis of RV pressure waveforms demonstrated RV-pulmonary vascular uncoupling and diastolic dysfunction in female, but not male, ERαMut PAB rats. Similarly, female, but not male, ERαMut exhibited increased RV fibrosis, comprised primarily of thick collagen fibers. There was an increased protein expression ratio of TIMP metallopeptidase inhibitor 1 (Timp1) to matrix metalloproteinase 9 (Mmp9) in female ERαMut compared with WT PAB rats, suggesting less collagen degradation. RNA-sequencing in female WT and ERαMut RV revealed kallikrein-related peptidase 10 (Klk10) and Jun Proto-Oncogene (Jun) as possible mediators of female RV protection during PAB. In summary, ERα in females is protective against RV-pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. ERα appears to be dispensable for RV adaptation in males. ERα may be a mediator of superior RV adaptation in female patients with PAH. NEW & NOTEWORTHY Using a novel loss-of-function mutation in estrogen receptor-α (ERα), we demonstrate that female, but not male, ERα mutant rats display right ventricular (RV)-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload, indicating a sex-dependent role of ERα in protecting against adverse RV remodeling. TIMP metallopeptidase inhibitor 1 (Timp1), matrix metalloproteinase 9 (Mmp9), kallikrein-related peptidase 10 ( Klk10 ), and Jun Proto-Oncogene ( Jun ) were identified as potential mediators in ERα-regulated pathways in RV pressure overload.

Purpose: Premature birth is associated with lasting effects, including lower exercise capacity and pulmonary function, and is acknowledged as a risk factor for cardiovascular disease. The aim was to evaluate factors affecting exercise capacity in adolescents born preterm, including the cardiovascular and pulmonary responses to exercise, activity level and strength., Methods: 21 preterm-born and 20 term-born adolescents (age 12-14 years) underwent strength and maximal exercise testing with thoracic bioimpedance monitoring. Baseline variables were compared between groups and ANCOVA was used to compare heart rate, cardiac output (Q) and stroke volume (SV) during exercise between groups while adjusting for body surface area., Results: Preterm-borns had lower maximal aerobic capacity than term-borns (2.0 ± 0.5 vs. 2.5 ± 0.5 L/min, p = 0.01) and lower maximal power (124 ± 26 vs. 153 ± 33 watts, p < 0.01), despite similar physical activity scores. Pulmonary function and muscular strength did not differ significantly. Although baseline Q and SV did not differ between groups, preterm adolescents had significantly lower cardiac index (Qi) at 50, 75 and 100% of maximal time to exhaustion, driven by SV volume index (SVi, 50% max time: 53.0 ± 9.0 vs. 61.6 ± 11.4; 75%: 51.7 ± 8.4 vs. 64.3 ± 11.1; 100%: 51.2 ± 9.3 vs. 64.3 ± 11.5 ml/m 2 , all p < 0.01), with similar heart rates., Conclusion: Otherwise healthy and physically active adolescents born very preterm exhibit lower exercise capacity than term-born adolescents. Despite similar baseline cardiovascular values, preterm-born adolescents demonstrate significantly reduced Qi and SVi during incremental and maximal exercise.

Preterm birth accounts for over 15 million global births per year. Perinatal interventions introduced since the early 1980s, such as antenatal glucocorticoids, surfactant, and invasive ventilation strategies, have dramatically improved survival of even the smallest, most vulnerable neonates. As a result, a new generation of preterm-born individuals has now reached early adulthood, and they are at increased risk of cardiovascular diseases. To better understand the sequelae of preterm birth, cardiovascular follow-up studies in adolescents and young adults born preterm have focused on characterizing changes in cardiac, vascular, and pulmonary structure and function. Being born preterm associates with a reduced cardiac reserve and smaller left and right ventricular volumes, as well as decreased vascularity, increased vascular stiffness, and higher pressure of both the pulmonary and systemic vasculature. The purpose of this review is to present major epidemiological evidence linking preterm birth with cardiovascular disease; to discuss findings from clinical studies showing a long-term impact of preterm birth on cardiac remodeling, as well as the systemic and pulmonary vascular systems; to discuss differences across gestational ages; and to consider possible driving mechanisms and therapeutic approaches for reducing cardiovascular burden in individuals born preterm.

Importance: Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood., Objective: To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magnetic resonance imaging (MRI)., Design, Setting, and Participants: This cross-sectional cohort study at an academic medical center included adolescents and young adults born moderately to extremely premature (20 in the adolescent cohort born from 2003 to 2004 and 38 in the young adult cohort born in the 1980s and 1990s) and 52 age-matched participants who were born at term and underwent cardiac MRI. The dates of analysis were February 2016 to October 2019., Exposures: Premature birth (gestational age ≤32 weeks) or birth weight less than 1500 g., Main Outcomes and Measures: Main study outcomes included MRI measures of biventricular volume, mass, and strain., Results: Of 40 adolescents (24 [60%] girls), the mean (SD) age of participants in the term and preterm groups was 13.3 (0.7) years and 13.0 (0.7) years, respectively. Of 70 adults (43 [61%] women), the mean (SD) age of participants in the term and preterm groups was 25.4 (2.9) years and 26.5 (3.5) years, respectively. Participants from both age cohorts who were born prematurely had statistically significantly smaller biventricular cardiac chamber size compared with participants in the term group: the mean (SD) left ventricular end-diastolic volume index was 72 (7) vs 80 (9) and 80 (10) vs 92 (15) mL/m2 for adolescents and adults in the preterm group compared with age-matched participants in the term group, respectively (P < .001), and the mean (SD) left ventricular end-systolic volume index was 30 (4) vs 34 (6) and 32 (7) vs 38 (8) mL/m2, respectively (P < .001). Stroke volume index was also reduced in adolescent vs adult participants in the preterm group vs age-matched participants in the term group, with a mean (SD) of 42 (7) vs 46 (7) and 48 (7) vs 54 (9) mL/m2, respectively (P < .001), although biventricular ejection fractions were preserved. Biventricular mass was statistically significantly lower in adolescents and adults born preterm: the mean (SD) left ventricular mass index was 39.6 (5.9) vs 44.4 (7.5) and 40.7 (7.3) vs 49.8 (14.0), respectively (P < .001). Cardiac strain analyses demonstrated a hypercontractile heart, primarily in the right ventricle, in adults born prematurely., Conclusions and Relevance: In this cross-sectional study, adolescents and young adults born prematurely had statistically significantly smaller biventricular cardiac chamber size and decreased cardiac mass. Although function was preserved in both age groups, these morphologic differences may be associated with elevated lifetime cardiovascular disease risk after premature birth.

Purpose: To explore the feasibility of using four-dimensional (4D) flow MRI to quantify blood flow and kinetic energy (KE) in the heart during strenuous exercise., Materials and Methods: For this prospective study, cardiac 4D flow MRI was performed in 11 healthy young adult participants (eight men, three women; mean age, 26 years ± 1 [standard deviation]) at rest and during exercise with an MRI-compatible exercise stepper between March 2016 and July 2017. Flow was measured in the ascending aorta (AAo) and main pulmonary artery (MPA). KE was quantified in the left and right ventricle. Significant changes in flow and KE during exercise were identified by using t tests. Repeatability was assessed with inter- and intraobserver comparisons and an analysis of internal flow consistency., Results: Nine participants successfully completed both rest and exercise imaging. Internal flow consistency analysis in systemic and pulmonary circulation showed average relative differences of 10% at rest and 16% during exercise. For flow measurements in the AAo and MPA, relative differences between observers never exceeded 6% in any vessel and showed excellent correlation, even during exercise. Relative differences were increased for KE, typically on the order of 30%, with poor interobserver correlation between measurements., Conclusion: Four-dimensional flow MRI can quantify increases in flow in the AAo and MPA during strenuous exercise and is highly repeatable. KE had reduced repeatability because of suboptimal segmentation methods and requires further development before clinical implementation. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Markl and Lee in this issue., (2020 by the Radiological Society of North America, Inc.)

Purpose: The goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1- 13 C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP 13 C compounds, HP 13 C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function., Methods: Eight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned 1 H/ 13 C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1- 13 C]pyruvate metabolism in the myocardium. This was coupled with 1 H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1- 13 C]pyruvate. For comparison to the [1- 13 C]pyruvate experiments, three female Sprague Dawley rats were imaged with 1 H cine MRI to determine myocardial function pre- and post-saline infusion., Results: We demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1- 13 C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1- 13 C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response., Conclusion: The infusion of [1- 13 C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rats exposed to postnatal hyperoxia develop right ventricular (RV) dysfunction, mild pulmonary hypertension, and dysregulated cardiac mitochondrial biogenesis when aged to one year, with the degree of cardiac dysfunction and pulmonary hypertension similar to that previously described in young adults born preterm. Here, we sought to understand the impact of postnatal hyperoxia exposure on RV hemodynamic and mitochondrial function across the life span. In Methods, pups from timed-pregnant Sprague-Dawley rats were randomized to normoxia or hyperoxia [fraction of inspired oxygen ( F I O 2 ), 0.85] exposure for the first 14 days of life, a commonly used model of chronic lung disease of prematurity. RV hemodynamic and mitochondrial function were assessed by invasive measurement of RV pressure-volume loops and by high-resolution respirometry at postnatal day 21 (P21), P90, and P365. In Results, at P21, hyperoxia-exposed rats demonstrated severe pulmonary hypertension and RV dysfunction, accompanied by depressed mitochondrial oxidative capacity. However, significant upregulation of mitochondrial biogenesis at P21 as well as improved afterload led to complete RV hemodynamic and mitochondrial recovery at P90. Mitochondrial DNA mutations were significantly higher by P90 and associated with significant late RV mitochondrial and hemodynamic dysfunction at P365. In conclusion, there appears to be a "honeymoon period" where cardiac hemodynamic and mitochondrial function normalizes following postnatal hyperoxia exposure, only to decline again with ongoing aging. This finding may have significant implications if a long-term pulmonary vascular screening program were to be developed for children or adults with a history of severe prematurity. Further investigation into the mechanisms of recovery are warranted. NEW & NOTEWORTHY Premature birth is associated with increased risk for cardiac dysfunction and failure throughout life. Here, we identify bimodal right ventricular dysfunction after postnatal hyperoxia exposure. Mitochondrial biogenesis serves as an early adaptive feature promoting recovery of cardiac hemodynamic and mitochondrial function. However, the accumulation of mitochondrial DNA mutations results in late mitochondrial and right ventricular dysfunction. This bimodal right ventricular dysfunction may have important implications for the development of screening programs in the preterm population.

In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants.

Purpose: The long-term implications of premature birth on autonomic nervous system (ANS) function are unclear. Heart rate recovery (HRR) following maximal exercise is a simple tool to evaluate ANS function and is a strong predictor of cardiovascular disease. Our objective was to determine whether HRR is impaired in young adults born preterm (PYA)., Methods: Individuals born between 1989 and 1991 were recruited from the Newborn Lung Project, a prospectively followed cohort of subjects born preterm weighing < 1500 g with an average gestational age of 28 weeks. Age-matched term-born controls were recruited from the local population. HRR was measured for 2 min following maximal exercise testing on an upright cycle ergometer in normoxia and hypoxia, and maximal aerobic capacity (VO 2max ) was measured., Results: Preterms had lower VO 2max than controls (34.88 ± 5.24 v 46.15 ± 10.21 ml/kg/min, respectively, p < 0.05), and exhibited slower HRR compared to controls after 1 and 2 min of recovery in normoxia (absolute drop of 20 ± 4 v 31 ± 10 and 41 ± 7 v 54 ± 11 beats per minute (bpm), respectively, p < 0.01) and hypoxia (19 ± 5 v 26 ± 8 and 39 ± 7 v 49 ± 13 bpm, respectively, p < 0.05). After adjusting for VO 2max , HRR remained slower in preterms at 1 and 2 min of recovery in normoxia (21 ± 2 v 30 ± 2 and 42 ± 3 v 52 ± 3 bpm, respectively, p < 0.05), but not hypoxia (19 ± 3 v 25 ± 2 and 40 ± 4 v 47 ± 3 bpm, respectively, p > 0.05)., Conclusions: Autonomic dysfunction as seen in this study has been associated with increased rates of cardiovascular disease in non-preterm populations, suggesting further study of the mechanisms of autonomic dysfunction after preterm birth.

The role of perinatal insults in the development of adult onset pulmonary hypertension (PH) is unclear. We surveyed patients with and without PH for a history of early life risk factors, and identified prematurity, oxygen use, and respiratory illness each as risk predictors for development of adult PH.

Rationale: Premature birth affects 10% of live births in the United States and is associated with alveolar simplification and altered pulmonary microvascular development. However, little is known about the long-term impact prematurity has on the pulmonary vasculature. Objectives: Determine the long-term effects of prematurity on right ventricular and pulmonary vascular hemodynamics. Methods: Preterm subjects ( n  = 11) were recruited from the Newborn Lung Project, a prospectively followed cohort at the University of Wisconsin-Madison, born preterm with very low birth weight (≤1,500 g; average gestational age, 28 wk) between 1988 and 1991. Control subjects ( n  = 10) from the same birth years were recruited from the general population. All subjects had no known adult cardiopulmonary disease. Right heart catheterization was performed to assess right ventricular and pulmonary vascular hemodynamics at rest and during hypoxic and exercise stress. Measurements and Main Results: Preterm subjects had higher mean pulmonary arterial pressures (mPAPs), with 27% (3 of 11) meeting criteria for borderline pulmonary hypertension (mPAP, 19-24 mm Hg) and 18% (2 of 11) meeting criteria for overt pulmonary hypertension (mPAP ≥ 25 mm Hg). Pulmonary vascular resistance and elastance were higher at rest and during exercise, suggesting a stiffer vascular bed. Preterm subjects were significantly less able to augment cardiac index or right ventricular stroke work during exercise. Among neonatal characteristics, total ventilatory support days was the strongest predictor of adult pulmonary pressure. Conclusions: Young adults born preterm demonstrate early pulmonary vascular disease, characterized by elevated pulmonary pressures, a stiffer pulmonary vascular bed, and right ventricular dysfunction, consistent with an increased risk of developing pulmonary hypertension.

Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.

Preterm birth temporarily disrupts autonomic nervous system (ANS) development, and the long-term impacts of disrupted fetal development are unclear in children. Abnormal cardiac ANS function is associated with worse health outcomes, and has been identified as a risk factor for cardiovascular disease. We used heart rate variability (HRV) in the time domain (standard deviation of RR intervals, SDRR; and root means squared of successive differences, RMSSD) and frequency domain (high frequency, HF; and low frequency, LF) at rest, as well as heart rate recovery (HRR) following maximal exercise, to assess autonomic function in adolescent children born preterm. Adolescents born preterm (less than 36 weeks gestation at birth) in 2003 and 2004 and healthy age-matched full-term controls participated. Wilcoxon Rank Sum tests were used to compare variables between control and preterm groups. Twenty-one adolescents born preterm and 20 term-born controls enrolled in the study. Preterm-born subjects had lower time-domain HRV, including SDRR (69.1 ± 33.8 vs. 110.1 ± 33.0 msec, respectively, P = 0.008) and RMSSD (58.8 ± 38.2 vs. 101.5 ± 36.2 msec, respectively, P = 0.012), with higher LF variability in preterm subjects. HRR after maximal exercise was slower in preterm-born subjects at 1 min (30 ± 12 vs. 39 ± 9 bpm, respectively, P = 0.013) and 2 min (52 ± 10 vs. 60 ± 10 bpm, respectively, P = 0.016). This study is the first report of autonomic dysfunction in adolescents born premature. Given prior association of impaired HRV with adult cardiovascular disease, additional investigations into the mechanisms of autonomic dysfunction in this population are warranted., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and ultimately right ventricular (RV) dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contractile properties is unknown. We used a rat model of BPD to examine the effect of hyperoxia-induced PH on RV contractile properties. We measured in vivo RV pressure as well as passive force, maximum Ca 2+ activated force, calcium sensitivity of force (pCa 50 ) and rate of force redevelopment ( k tr ) in RV skinned trabeculae isolated from hearts of 21-and 35-day old rats pre-exposed to 21% oxygen (normoxia) or 85% oxygen (hyperoxia) for 14 days after birth. Systolic and diastolic RV pressure were significantly higher at day 21 in hyperoxia exposed rats compared to normoxia control rats, but normalized by 35 days of age. Passive force, maximum Ca 2+ activated force, and calcium sensitivity of force were elevated and cross-bridge cycling kinetics depressed in 21-day old hyperoxic trabeculae, whereas no differences between normoxic and hyperoxic trabeculae were seen at 35 days. Myofibrillar protein analysis revealed that 21-day old hyperoxic trabeculae had increased levels of beta-myosin heavy chain (β-MHC), atrial myosin light chain 1 (aMLC1; often referred to as essential light chain), and slow skeletal troponin I (ssTnI) compared to age matched normoxic trabeculae. On the other hand, 35-day old normoxic and hyperoxic trabeculae expressed similar level of α- and β-MHC, ventricular MLC1 and predominantly cTnI. These results suggest that neonatal exposure to hyperoxia increases RV afterload and affect both the steady state and dynamic contractile properties of the RV, likely as a result of hyperoxia-induced expression of β-MHC, delayed transition of slow skeletal TnI to cardiac TnI, and expression of atrial MLC1. These hyperoxia-induced changes in contractile properties are reversible and accompany the resolution of PH with further developmental age, underscoring the importance of reducing RV afterload to allow for normalization of RV function in both animal models and humans with BPD.

Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular (RV) hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of RV dysfunction and ventricular-vascular uncoupling after prematurity, remain poorly defined. Using an established model of prematurity-related lung disease, pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (fraction of inspired oxygen, 0.85) exposure for the first 14 days of life. After aging to 1 year in standard conditions, rats underwent hemodynamic assessment followed by tissue harvest for biochemical and histological evaluation. Aged hyperoxia-exposed rats developed significantly greater RV hypertrophy, associated with a 40% increase in RV systolic pressures. Although cardiac index was similar, hyperoxia-exposed rats demonstrated a reduced RV ejection fraction and significant RV-pulmonary vascular uncoupling. Hyperoxia-exposed RV cardiomyocytes demonstrated evidence of mitochondrial dysregulation and mitochondrial DNA damage, suggesting potential mitochondrial dysfunction as a cause of RV dysfunction. Aged rats exposed to postnatal hyperoxia recapitulate many features of young adults born prematurely, including increased RV hypertrophy and decreased RV ejection fraction. Our data suggest that postnatal hyperoxia exposure results in mitochondrial dysregulation that persists into adulthood with eventual RV dysfunction. Further evaluation of long-term mitochondrial function is warranted in both animal models of premature lung disease and in human adults who were born preterm.

Pediatric pulmonary vascular disease (PVD) and pulmonary hypertension (PH) represent phenotypically and pathophysiologically diverse disease categories, contributing substantial morbidity and mortality to a complex array of pediatric conditions. Here, we review the multifactorial nature of pediatric PVD, with an emphasis on improved recognition, phenotyping, and endotyping strategies for pediatric PH. Novel tailored approaches to diagnosis and treatment in pediatric PVD, as well as the implications for long-term outcomes, are highlighted.

Estrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2's RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH., (Copyright © 2015 the American Physiological Society.)

The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0-4 or 0-10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults., (Copyright © 2015 the American Physiological Society.)