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Objectives:Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies.Methods:Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD).Results:We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA‐CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%).Conclusions:Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD.

Abstract Background It is not clear if the increase in the number of esophagogastroduodenoscopies (EGDs) performed has any significant effect on the rate of lymphocytic duodenosis (LD) reporting in children and adolescents and whether it correlates with abnormal gastric and/or esophageal pathology.” Methods We performed a single-center retrospective study using the Mayo Clinic electronic health record and pathology database. We reviewed all EGD procedures performed in children and adolescents (<18 years) between January 1, 2000, and December 31, 2018, and identified two groups, the LD group and matched age and sex control group (normal duodenal biopsies). We evaluated the correlation of LD rate with the yearly number of EGDs performed and the presence of abnormal gastric and/or esophageal pathology. Results Of 11,870 EGDs performed, we identified 338 (3%) individuals with LD and 390 (3%) randomly selected controls, with a mean (SD) age of 9.6 (5.3) and 11.7 (5.0) years, respectively. Based on logistic regression analysis, abnormal gastric histology was associated with the presence of LD when compared with controls (odds ratio, 2.85; 95% CI, 2.05–3.97; P < 0.001). The rate of LD-positive biopsies per year was highly correlated with the number of EGDs performed (ρ = 0.931; 95% CI, 0.826–0.974; P < 0.001). Conclusion The rate of LD reporting is correlated with the number of EGDs performed and is more likely seen in children and adolescents with abnormal gastric histology.

Introduction: Chronic elevation of left heart filling pressure causes pulmonary vascular remodeling, pulmonary hypertension, and right heart dysfunction. Although diastolic dysfunction is relatively common in patients with coarctation of aorta (COA), there are limited data about the prevalence and prognostic implications of pulmonary hypertension and right heart dysfunction in this population. The purpose of the study was to assess right heart function and hemodynamics in patients with COA, and to determine the relationship between right heart indices and clinical outcomes. Methods: Right heart structure, function and hemodynamics were assessed with these indices: right atrial (RA) volume, RA pressure, RA reservoir strain, right ventricular (RV) global longitudinal strain, RV end-diastolic area, RV systolic pressure, and tricuspid regurgitation severity. These indices were used to generate a composite right heart hemodynamic score (RHHS), range 0-5. We then assessed the relationship between RHHS and primary outcome (death/transplant) and secondary outcomes (heart failure hospitalization and hepatorenal function). Results: Of 821 COA patients, RA dysfunction, RV dysfunction, and pulmonary hypertension were present in 16%, 14%, and 20% of patients respectively. RHHS was independently associated with primary and secondary outcomes (p<0.001). For every unit increase in RHHS, we observed 83% increase in death/transplant and 71% increase in heart failure hospitalization. Conclusions: The current study underscores an important point, which is that COA is not just a disease of the left heart but can result in right heart dysfunction, and that the onset of right heart dysfunction is associated with adverse outcomes.

Introduction: Valvuloarterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Since patients with coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with ≥moderate AS (AS-COA group) will have higher Zva, symptomatic progression, and cardiovascular events, as compared to non-COA patients with similar AS severity (AS group). Methods: 1:1 propensity matching of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient. Results: The AS-COA group had higher Zva (4.2±0.6 vs 3.5±0.4 mmHg/ml*m 2 , p<0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% vs 51%, p<0.001). Pre-operative Zva was independently associated with cardiac remodeling (r=0.66, p<0.001) and symptomatic progression (HR 1.08, 1.05-1.12, per mmHg/ml*m 2 increase in Zva). Of 172 patients, 117 underwent aortic valve replacement (AVR). The AS-COA group had higher residual Zva(3.3±0.5 vs 2.4±0.4 mmHg/ml*m 2 , p<0.001), less robust LV mass index (LVMI) regression at 1-year post-AVR, and higher 5-year incidence of cardiovascular events. Post-operative Zva was independently associated with LVMI regression (r=-0.46, p<0.001) and cardiovascular events (HR 1.06, 1.02-1.10, per mmHg/ml*m 2 increase in Zva). Conclusions: Adults with repaired COA repair and moderate-severe AS had higher LV global pressure load, cardiac remodeling, symptomatic progression, and cardiovascular events as compared to non-COA patients with similar severity of AS. Zva can identify patients at risk for adverse outcomes, and perhaps should be used for risk stratification with regards to timing of AVR.

Background The relationship between office vs. ambulatory blood pressure (BP) indices are well-studied in patients with essential hypertension and based on these data, it is known that the average 24-h ambulatory BP is typically lower than office BP. However, emerging data show that office SBP underestimates arterial afterload in patients with coarctation of aorta (COA), and a minimal increase in stroke volume during low-intensity exercise results in an exaggerated rise in SBP as compared to those with essential hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with essential hypertension. Methods Case-control study of 118 COA patients and 118 patients with essential hypertension matched by age, sex, BMI and office SBP. Results Although both groups had similar office SBP (132 ± 17 mmHg) by design, the COA group had paradoxical increases in 24-h ambulatory SBP (135 ± 14 vs. 126 ± 13; P < 0.001) and daytime ambulatory SBP (142 ± 16 vs. 130 ± 13; P < 0.001), and less nocturnal dipping (−3 ± 5 vs. −9 ± 4; P < 0.001). The COA group also had a higher prevalence of masked hypertension [36 (31%) vs 14 (12%); P < 0.001), and worse arterial function indices. Conclusion These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating essential hypertension guidelines recommendations to the treatment of COA. It also provides the rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population.

Abstract Background The relationship between office vs ambulatory blood pressure (BP) indices is well-studied in patients with idiopathic hypertension, and based on these data, it is known that average 24-hour ambulatory BP is typically lower than office BP. However, emerging data show that office systolic BP (SBP) underestimates arterial afterload in patients with coarctation of aorta (COA), and minimal increase in stroke volume during low intensity exercise results in exaggerated rise in SBP as compared to those with idiopathic hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with idiopathic hypertension. Methods Case-control study of 118 COA patients and 118 patients with idiopathic hypertension matched by age, sex, body mass index and office SBP. Results Although both groups had similar office SBP (132±17 mmHg) by design, the COA group had paradoxical increases in 24-hour ambulatory SBP (135±14 vs 126±13, p&lt;0.001) and daytime ambulatory SBP (142±16 vs 130±13, p&lt;0.001), and less nocturnal dipping (−3±5 vs −9±4, p&lt;0.001). The COA group also had a higher prevalence of masked hypertension (36 [31%] vs 14 [12%], p&lt;0.001), and worse arterial function indices. Conclusion These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating idiopathic hypertension guidelines recommendations to the treatment of COA. It also provides rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population. Funding Acknowledgement Type of funding sources: None.

Abstract Background Left atrial dysfunction (LAD) and left ventricular diastolic dysfunction (LVDD) has been described in patients with coarctation of aorta (COA). However, it is unknown whether LA function and LV diastolic function indices can be used for prognostication in this population. The purpose of this study was to determine whether LAD and LVDD were associated with mortality in adults with COA. We hypothesized that LA and LV diastolic function indices will predict transplant-free survival in COA patients. Methods Retrospective study of COA patients (age ≥18) at Mayo Clinic (2000–2018). LVDD was determined using the 2016 guidelines for LVDD assessment, and LAD was assessed using LA reservoir strain. Results Of 721 patients, LV diastolic function could be determined in 635 (88%), while 86 (12%) were classified as indeterminate diastolic function. Of 635 patients, 414 (65%) had no LVDD, while 146 (23%), 53 (8%), and 22 (4%) had grade I/II/III LVDD respectively. The mean LA reservoir strain was −39±11%, and patients were divided into quartiles: top quartile (reference group), mild LAD, moderate LAD, and severe LAD. Of 635 patients, 49 died and 4 underwent heart transplant. On multivariate analysis, Grade III diastolic dysfunction (but not Grade I and II) was associated with mortality as compared to normal diastolic function. On the other hand, there was an incremental risk of mortality across LA strain quartiles: mild LAD (HR 1.16, 1.04–2.06), moderate LAD (HR 1.75, 1.27–3.58), and severe LAD (HR 3.49, 1.88–7.16). Of the 86 patients with indeterminate diastolic function, LAD was associated with a lower 5-year transplant-free survival as compared to normal LA function (83% vs 91%, p=0.06). Conclusions LAD (but not LVDD) was associated with incremental risk of mortality, and thus can be used for prognostication in all patients including those with indeterminate diastolic function. Although the current study did not identify a consistent relationship between LVDD severity classifications and mortality among COA patients, it does not imply that LVDD is benign. Rather it suggests that the conventional criteria for LVDD severity classifications may not be generalizable to every disease subgroup Funding Acknowledgement Type of funding sources: None.

Abstract Background There are limited data about outcomes after repair of native coarctation of aorta (COA) in adulthood. The purpose of this study was to describe the procedural outcomes, hemodynamic improvement, regression of LV hypertrophy and cardiovascular events in adults undergoing repair of native COA. Methods The primary outcomes were procedural complications, re-interventions, and hemodynamic improvement (residual COA gradient &lt;20 mmHg) after COA repair. The secondary outcomes were improvement in the severity of hypertension, regression of left ventricular mass index (LVMI), and incidence of cardiovascular events (atrial fibrillation, heart failure hospitalization, and cardiovascular death) after COA repair. Clinical and imaging indices were assessed pre-intervention, and at 1-year (Y1) and 3-years (Y3) post-intervention. Results A total of 172 patients (age 38 [27–48]) underwent COA repair (surgical 161; transcatheter 11). There were no procedural deaths, and all patients had residual COA gradient &lt;20 mmHg. One patients that received transcatheter stent therapy required re-dilation of stent at 12 months post-intervention. There as a reduction in the prevalence of patients requiring anti-hypertensive therapy from 73% (pre-intervention) to 59% and 64% at Y1 and Y3 respectively. However, 72% and 69% of the patients still had systolic blood pressure &gt;130 mmHg (stage 1 and 2 hypertension) at Y1 and Y3 respectively. As compared to patients without hypertension at Y1, patients with stage 1 and stage 2 hypertension had less robust LVMI regression (% change in LVMI 12±5% vs 9±6% vs 5±3%, p&lt;0.001). Hypertension (HR 1.16, 1.05–1.27) and LVMI regression (HR 0.86, 0.81–0.90) were independently associated with cardiovascular events. Conclusions Persistent hypertension was common after repair of native COA in adults. Hypertension (including stage 1 hypertension) was associated with suboptimal regression of LVMI and cardiovascular events. These results are concerning, and highlight the importance of early COA diagnosis and repair, and optimal medical therapy for hypertension after COA repair. Funding Acknowledgement Type of funding sources: None.

Abstract Background Certain factors such as left ventricular (LV) geometry and loading conditions affect the validity and reliability of LV ejection fraction (LVEF) as a true measure of LV contractility. LV global longitudinal strain (LVGLS) is less sensitive to these factors, and it has superior prognostic performance in patients with acquired heart disease. The purpose of this study was to determine the clinical implications of using LVGLS (instead of LVEF) as the measure of LV systolic function in adults with Ebstein anomaly given the inherent abnormalities of LV geometry and preload in this population. Methods Retrospective cohort study of 673 adults with Ebstein anomaly (2003–2018). We hypothesized that LVGLS had a stronger correlation with heart failure indices and transplant-free survival compared to LVEF. Results Compared to LVEF, LVGLS had stronger correlations with cardiac index (r=0.46 vs r=0.21, p=0.007), glomerular filtration rate (r=0.57 vs r=0.19, p&lt;0.001), and NT-proBNP (r=−0.64 vs r=−0.41, p=0.01). Of 673 patients, 514 (76%) had normal LV systolic function (LVGLSNormal-LVEFNormal), 87 (13%) had subclinical LV dysfunction (LVGLSLow-LVEFNormal) and 66 (10%) had overt LV dysfunction (LVGLSLow-LVEFLow). Compared to the overt LV dysfunction group, the subclinical LV dysfunction group had similar 10-year transplant-free survival (64% vs 63%, p=0.6), but were less likely to be on heart failure therapy (12% vs 82%, p&lt;0.001). LVGLS (but not LVEF) was the independent predictor of transplant-free survival Conclusions LVGLS provided more robust risk stratification and prognostication than LVEF in patients with Ebstein anomaly, and patients with low LVGLS had reduced transplant-free survival regardless of LVEF. The use of LVGLS (rather than LVEF) as the measure of LV systolic function has important clinical implications with regards to initiation of medical and surgical therapies. Funding Acknowledgement Type of funding sources: None.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant hereditary disorder that results in arteriovenous malformations (AVMs) in the nose, mucocutaneous surfaces and visceral organs, including lung, brain, liver, bowel and rarely spinal cord. We describe a case of a young child with HHT who presented with acute paraparesis due to acute thrombosis of a spinal perimedullary arteriovenous fistula. Patient underwent coil embolization of spinal arteriovenous shunt with resolution of clinical symptoms. This case highlights the possibility of catastrophic complications in young children with HHT, the potential preventive role of screening for spinal AVMs in HHT and the importance of timely intervention.