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In univentricular (Fontan) physiology, peripheral and splanchnic vascular tone may be raised to counteract reduced cardiac output (CO) and elevated central venous pressure and thus maintain vital organ perfusion. This could negatively affect the normal cardiovascular response to food ingestion, where mesenteric vasodilation and a concurrent rise in CO are central. We sought to elucidate this using rapid cardiovascular MRI. Thirty fasting subjects (50% controls, 40% women and 60% men) ingested a standardized meal. Responses over ~50 min in mean arterial pressure (MAP), CO, and blood flow in all major aortic branches were measured, and regional vascular impedance (Z(0)) was calculated. Differences from baseline and between groups were assessed by repeated-measures mixed models. Compared with the control group, the Fontan patient group had greater fasting Z(0) of the legs and kidneys, resulting in greater systemic Z(0) and similar MAP. They further had similar blood flow to the digestive organs at baseline, despite larger variation in mesenteric resistance. Postprandially, blood flow to the legs decreased in the control group but not in the Fontan patient group. Increases in CO and superior mesenteric blood flow were similar in both groups, but the celiac response was blunted in the Fontan patient group. No significant differences in MAP responses were observed. In conclusion, alterations in vascular tone to counteract adverse hemodynamics and raised hepatic afterload may blunt vasoreactivity in the legs and the celiac axis in Fontan physiology. Further study is needed to determine whether blunted celiac or mesenteric vasoreactivity is linked to deteriorating hemodynamics and poor prognosis in Fontan patients. NEW & NOTEWORTHY Novel data on cardiovascular physiology in response to a meal in Fontan patients are presented. Using a previously validated dynamic MRI protocol, we demonstrated that the usual increase in cardiac output and the dilation of the superior mesenteric artery are preserved in clinically well Fontan patients. In contrast, vasoconstriction of the legs may have prevented redistribution of blood flow from this region in response to the meal. This may also affect responses to other types of stress. Celiac vasodilation was also absent in Fontan patients. This may be due to abnormal hepatic circulation. The proposed protocol may be used to study Fontan complications secondary to abnormal regional hemodynamics.

Background: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular disease, including heart failure. Although linked to obesity and hypertension, its pathogenesis is multifactorial. Blunted postprandial sympathetic regulation of gut blood flow has been observed in overweight animals and suggested as a promotor of hypertension and LVH. We hypothesized that blunted postprandial superior mesenteric blood flow responses would be more common in overweight humans and associated with increased blood pressure and LVH. Methods: Left ventricular dimensions and hemodynamic responses to a standardized high-calorie liquid meal were measured in healthy adolescents (n=82; 39 overweight/obese) by magnetic resonance imaging. Covariates such as body mass index, blood pressure, Tanner score, and an index of insulin resistance were included in multiple regression models to examine the independent associations of mesenteric flow response with blood pressure status and LVH. Results: Food ingestion increased cardiac output (Δmean, 0.45 [SD, 0.62] L·min −1 ; P =3.8×10 −8 ) and superior mesenteric artery flow (Δmean, 0.76 [SD, 0.35] L·min −1 ; P =4.2×10 −31 ). A blunted mesenteric flow response was associated with increased left ventricular mass (B=−12.7 g·m −2.7 per L·min −1 ·m − 0.92 ; P =6×10 −5 ) and concentric LVH (log likelihood, −9.9; P =0.001), independently of known determinants of LVH, including body mass index. It was also associated with elevated systolic blood pressure (B=−18.0 mm Hg per L·min −1 ·m − 0.92 ; P =0.001), but this link did not explain the association with left ventricular mass. Conclusions: Postprandial mesenteric vascular dysfunction is associated with LVH and hypertension, independently of common risk factors for those conditions. These findings highlight a new, independent marker of cardiovascular risk in the young.

Cardiometabolic (CM) disorders begin earlier than previously thought. Better understanding of drivers of CM risk in the young is needed to address this. Adiposity is an established concern but studies largely rely on indirect markers eg. body mass index (BMI) to assess it. BMI is known to reflect both skeletal size & adiposity. This study aimed to compare effects of BMI with independent effects of liver fat percentage (LFP), fat-free mass (FFM), & subcutaneous (SAT) & visceral (SAT) adipose tissue on CM risk in teenagers. Healthy teens [N=82; Age 13–19y; 39 overwt/obese; 46F/36M] had volumetric magnetic resonance (MR) tissue mapping (neck-to-knee T2*-IDEAL). BMI z-score (WHO age/sex reference; zBMI), systolic BP (SBP), fasting blood (TRIGlyceride; CHOLesterol; HDL; IL6; CRP; white blood cells [WBC]; LEPTIN), & insulin & glucose response [0, 20, 40, 60, 90, 120 & 240 min] to a mixed meal (75g glucose + cream) were assessed. Indices of insulin resistance (HOMA-IR) and sensitivity (MATSUDA-IS) were derived from fasting measures & integrated meal responses, respectively. Independent effects of LFP, FFM, SAT & VAT were tested by conditional regression in a 4 compartment model (4CM). Higher zBMI was positively correlated with TRIG, IL6, CRP, WBC, HOMA-IR, LEPTIN & SBP, & inversely with HDL & MATSUDA-IS (Table). The 4CM showed that SAT was responsible for most of these links but VAT contributed to lower MATSUDA-IS, SAT was positively correlated with CHOL (zBMI was not), & FFM was a significant predictor of HDL, CRP & LEPTIN. It was solely responsible for the association of zBMI with SBP. There were no independent effects of LFP. zBMI was strongly driven by both FFM & SAT, limiting its ability to differentiate effects of skeletal size from those of adiposity. Correlation coefficients BMI TRIG (mmol/L) CHOL (mmol/L) HDL (mmol/L) IL6 (pg/mL) CRP (mg/L) WBC (x109/L) HOMA-IR MATSUDA-IS LEPTIN (ng/mL) SBP (mmHg) Median (IQR) 23.4 (20.3, 29.6) 0.64 (0.52, 1.00) 3.5 (3.2, 4.0) 1.2 (1.0, 1.3) 4.0 (2.6, 6.7) 0.67 (0.22, 1.80) 5.6 (4.7, 7.1) 1.5 (0.8, 2.2) 9.3 (5.5, 12.6) 11.1 (2.1, 24.6) 114 (108, 120) zBMI 0.33§ 0.16 −0.43‡ 0.27¶ 0.69‡ 0.51‡ 0.54‡ −0.48‡ 0.77‡ 0.27¶ LFP 0.18 −0.06 0.18 0.19 0.00 −0.06 0.11 0.23 −0.21 −0.00 0.13 VAT 0.07 0.18 0.08 −0.22 0.09 −0.00 0.12 0.19 −0.35§ −0.08 0.09 SAT 0.89‡ 0.37§ 0.33§ −0.25¶ 0.37§ 0.57‡ 0.45† 0.61‡ −0.44† 0.85‡ −0.10 FFM 0.86‡ 0.04 −0.16 −0.34§ −0.02 0.31¶ −0.01 0.25 −0.25 0.39§ 0.34§ ¶P We found associations of zBMI with CM risk in teens that are usually interpreted as due to adiposity. Although SAT was largely responsible, FFM & VAT were important too & the link between BMI & SBP was due solely to FFM. Associations of CM risk factors with BMI may reflect non-adipose tissue effects & should be interpreted cautiously in the young. Acknowledgement/Funding Alexander Jones is funded by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/22/33479)

International audience; Computer models of the heart are of increasing interest for clinical applications due to their discriminative and predictive abilities. However the number of simulation parameters in these models can be high and expert knowledge is required to properly design studies involving these models, and analyse the results. In particular it is important to know how the parameters vary in various clinical or physiological settings. In this paper we build a data-driven model of cardiovascular parameter evolution during digestion, from a clinical study involving more than 80 patients. We first present a method for longitudinal parameter estimation in 3D cardiac models, which we apply to 21 patient-specific hearts geometries at two instants of the study, for 6 parameters (two fixed and four time-varying parameters). From these personalised hearts, we then extract and validate a law which links the changes of cardiac output and heart rate under constant arterial pressure to the evolution of these parameters, thus enabling the fast simulation of hearts during digestion for future patients.

A 32-year-old woman was seen for acute chest pain radiating to the neck and arms. The paramedical team witnessed her cardiac arrest on arrival and successfully defibrillated ventricular fibrillation by a single shock. After a stable transfer to the local hospital, she had a second witnessed arrest necessitating further defibrillation. History revealed good functional capacity and no other cardiac symptoms. Examination showed clear lungs, normal heart sounds, a normal abdomen, a blood pressure of 110/79 mm Hg, and an oxygen saturation of 100% (Figure I in the Data Supplement). The ECG showed signs of inferolateral infarction. Cardiac troponin I was 1.06 ng/mL. Telemetry confirmed intermittent nonsustained ventricular tachycardia and sinus bradycardia. Her medical therapy included bisoprolol 2.5 mg and warfarin (International Standardized Ratio, 1.7). Because of tricuspid atresia, transposition of the great arteries, pulmonary stenosis, and ventricular septum defect, she had undergone superior cavo-pulmonary shunt (Glenn) aged 4 years and atrio-pulmonary (Fontan) connection aged 7 years. Three years before, recurrent supraventricular tachycardia necessitated multiple electrophysiological studies, with ablation of focal right atrial tachycardias and cavo-tricuspid isthmus-dependent flutter. Echocardiography showed preserved ventricular function, mild flow acceleration across the subaortic ventricular septum defect, mild mitral regurgitation, as well as dilated systemic and hepatic veins (Movies V and VI in the Data Supplement). Computed tomography (CT) of the pulmonary arteries (PA; computed tomography pulmonary angiogram) was subsequently performed, reporting a large opacification defect in the proximal left PA, suggestive of pulmonary embolism (Figure 1). Cardiac magnetic resonance imaging (CMR) thereafter showed a patent Fontan pathway, no thrombi, and normal pulmonary arborization. The coronary sinus, the right atrial, the cardiac, hepatic, and the systemic veins were severely distended (inferior vena cava; Figures 2 and 3; Movies I-III in the Data Supplement), with diastolic flow reversal in the inferior vena cava. No systemic-to-pulmonary collaterals (SPC) …

Fragestellung: Eine fett- und kohlenhydratreiche Diat lost bei Erwachsenen eine inflammatorische Reaktion mit negativen Effekten auf die vaskulare Endothelfunktion aus. Wenig ist hingegen uber die Auswirkungen einer solchen Ernahrung bei Jugendlichen sowie ihre Interaktion mit anderen Risikofaktoren mit Hinblick auf die langfristige kardiovaskulare Morbiditat bekannt. Zielsetzung war es, die vaskular-inflammatorische Reaktion auf kalorienreiches Essen bei Jugendlichen zu beschreiben und auf ihren Zusammenhang mit dem arteriellen Blutdruck (BD) hin zu untersuchen. Methoden: Nach Messung deren Ruheblutdruckes wurde 20 Probanden (Alter 13–19 Jahre) eine kalorienreiche Mahlzeit verabreicht (300mL Doppelsahne; 89 g Maltosesyrup; Energiegehalt 1.635 kcal). Die Biomarker Cathepsin-S, vascular cell adhesion molecule-1 (vCAM-1) und intercellular adhesion molecule-1 (iCAM-1) wurden vor Verzehr der Mahlzeit, sowie 1, 2 und 4 Stunden danach gemessen. Die kontinuierliche Interaktion zwischen systolischem Blutdruck und den Biomarkern im Blut wurde in einer Zeitreihen-Regressionsanalyse ermittelt. Ergebnisse: Jugendliche mit einem hoheren systolischen Ruheblutdruck hatten signifikant hohere Cathepsin-S- and vCAM-1-Spiegel nach 1 Stunde (p = 0.004 und p = 0.03), sowie hohere iCAM-1 Werte nach 2 und 4 Stunden postprandial, als solche mit einem niedrigeren Blutdruck (p< 0.01). Zu Ausgang wurde kein Zusammenhang zwischen systolischem Blutdruck, Cathepsin-S, vCAM-1 und iCAM-1 beobachtet. Der diastolische Blutdruck zeigte keine Assoziation. Schlussfolgerung: Unsere Studie zeigt erstmalig, dass Jugendliche mit hoherem systolischem Blutdruck verstarkt mit inflammatorischen Prozessen auf eine kohlenhydrat- und fettreiche Mahlzeit reagieren. Die Richtung dieser Assoziation kann nicht in dieser Querschnittsanalyse festgestellt werden. Unsere Ergebnisse stehen allerdings im Einklang mit der Hypothese, dass eine erhohte Neigung zur Gefasinflammation durch ungesundes Essen die Entstehung von Hypertonie fruh begunstigt und dass solche Prozesse bereits in der Kindheit beginnen konnten.

Objective Biomarkers play a pivotal role in heart failure (HF) management. Reference values and insights from studies in adults cannot be extrapolated to the paediatric population due to important differences in pathophysiology and compensatory reserve. We assessed the diagnostic utility of four novel biomarkers in paediatric HF. Methods Midregional (MR) pro-atrial natriuretic peptide (proANP), soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), MR-pro-adrenomedullin (proADM) and N-terminal pro-B natriuretic peptide (NT-proBNP) were measured in 114 patients and 89 controls. HF was defined as the presence of HF symptoms and/or abnormal systolic ventricular function. Receiver-operating characteristics were plotted, and the area under the curve (AUC) was measured. This was repeated for subgroups with cardiomyopathy and congenital heart disease (CHD). Ventricular systolic function was measured by magnetic resonance or echocardiography. Reference values were calculated according to the current guidelines. Results The AUC for diagnosing HF was 0.76 for MR-proANP (CI 0.70 to 0.84) and 0.82 for NT-proBNP (CI 0.75 to 0.88). These parameters performed similarly in the subgroups with CHD and cardiomyopathy. By contrast, MR-proADM, GDF-15 and sST2 performed poorly. When used in conjunction with NT-proBNP, no parameter added significantly to its diagnostic accuracy. NT-proBNP, MR-proANP, GDF-15 and sST2 could accurately discriminate between patients with preserved and patients with poor functional status. In a subset of patients with dilated cardiomyopathy, NT-proBNP, MR-proANP, MR-proADM and GDF-15 were associated with poor LV function. Conclusions MR-proANP could accurately detect HF in children and adolescents. Its diagnostic performance was comparable with that of NT-proBNP, regardless of the underlying condition. Reference values are presented.

Background: The ingestion of food is known to increase mesenteric blood flow significantly. However, it remains unknown whether this increased flow demand to the intestine is compensated by an increase in total cardiac output (CO) alone, or by redistribution of blood flow from other organs, caused by changes in organ-specific vascular resistance. Non-invasive studies on the vascular response of small arteries have been scarce due to technical constraints, as conventional as well as MRI-based methods for non-invasive flow assessment are time-consuming and observer-dependent. We present a novel, comprehensive phenotyping model of the hemodynamic changes caused by the ingestion of a high-energy liquid meal, assessed by novel MRI sequences for the rapid assessment of small vessel blood flow.

Ingestion of food is known to increase mesenteric blood flow. It is not clear whether this increased flow demand is compensated by a rise in cardiac output (CO) alone or by redistribution of blood flow from other organs. We used a new comprehensive imaging method to assess the human cardiovascular response to food ingestion. Following a 12-h fast, blood flow in segments of the aorta and in organ-specific arteries, and ventricular volumes were assessed in 20 healthy adults using MRI at rest and following ingestion of a high-energy liquid meal. Systemic vascular resistance (SVR) fell substantially and CO rose significantly. Blood pressure remained stable. These changes were predominantly driven by a rapid fall in mesenteric vascular resistance, resulting in over four times more intestinal blood flow. Renal vascular resistance also declined but less dramatically. No changes in blood flow to the celiac territory, the brain, or the limbs were observed. In conclusion, this is the first study to fully characterize systemic and regional changes in vascular resistance after food ingestion in humans. Our findings show that the postprandial drop in SVR is fully compensated for by increased CO and not by redistribution of blood from other organs. With the exception of a modest increase in renal blood flow, there was no evidence of altered blood flow to nondigestive organs. The proposed oral food challenge protocol can be applied safely in an MRI environment and may be useful for studying the involvement of the gut in systemic or cardiovascular disease.

Nonfamilial cardiomyopathies in childhood have been only sporadically ascribed to endocrine disorders. We report on a 4-month-old male infant presenting with Cushing’s syndrome associated with excessive body weight (8.9 kg; >97th percentile) and features of virilization (Tanner stage 2 for pubic hair development). Abdominal sonography showed a large adrenal tumor. Echocardiography revealed myocardial hypertrophy with severe subaortic obstruction. Blood tests showed excessive androgen and cortisol serum levels with absent circadian rhythm as well as suppressed corticotropin. Urine catecholamine levels were within the normal range. Tumor resection with general anesthesia was performed after preparation with antihypertensive and anticongestive drug therapy. Continuous intravenous hydrocortisone substitution was started intraoperatively and subsequently tapered and switched to oral administration after 12 days. A gradual reduction in glucocorticoid substitution and its discontinuation after a total duration of 9 months were well tolerated. Histopathologic workup revealed an adrenocortical tumor of intermediate dignity. Postoperative tumor staging excluded both residual primary tumor and metastases. Both a normalization of body weight and myocardial mass were observed. The present article is, to our knowledge, the first to describe severe hypertrophic obstructive cardiomyopathy caused by an adrenocortical tumor and provides novel detailed data on postoperative glucocorticoid management. * Abbreviations: ACT — : adrenocortical tumor HOCM — : hypertrophic obstructive cardiomyopathy LVOT — : left ventricular outflow tract

The aortic velocity time integral (VTI) is an echocardiographic tool used to estimate cardiac output (CO) by multiplying it with the aortic valve (AV) area and heart rate (HR). Inaccurate measurement of AV diameter will lead to squared miscalculation of CO. The aortic VTI itself can serve as a left-ventricular (LV) output parameter. The normal range of aortic VTI in adulthood is relatively stable, compared with childhood, but reference data are lacking. The aim of this study was to establish reference values of VTI in infants, children, and adolescents. A retrospective analysis of 1223 echocardiographic examinations of healthy children (age 0–20 years, body surface area [BSA] 0.11–2.23 m2) was performed. Data were correlated with age, BSA, and HR, and age subgroups with normal distribution were determined. Interobserver and intraobserver variability was calculated. Aortic VTI ranged from mean 13.8 cm (10.0–18.4 cm 5–95th percentile) in neonates to 25.1 cm (19.6–32.8 cm 5–95th percentile) in children >17 years of age and had a positive correlation with age (r = 0.685, p < 0.001), BSA (r = 0.645, p < 0.001) and a negative correlation with HR (r = −0.710, p < 0.001). Interobserver and intraobserver variability were excellent (3.9 ± 3.1 and 4.6 ± 3.7 %, respectively). Calculated mean values and percentile charts for the different age groups can serve as reference data to easily judge LV output in patients with or without congenital heart disease without enlargement or dysfunction of the AV.

The contribution of atrial contraction to cardiac output (CO) has been the subject of extensive research but has yet to be quantified adequately in children and adolescents. Patients with third-degree atrioventricular (AV) block treated with pacemakers (PMs) are ideal candidates to assess the atrial contribution to CO by repeated measurements in single-chamber pacing mode (VVIR) and dual-chamber pacing mode (DDD/VDD). Hemodynamic measurements in children are often complicated by technical restrictions, but more recently a noninvasive method involving inert gas rebreathing has become available, which is an excellent tool for this age group. We examined 10 patients (6 female patients, mean age 14.5 ± 2.5 years, range 11 to 18) with congenital complete AV block treated with dual-chamber PM. Using an inert gas rebreathing device (Innocor) we measured CO in DDD/VDD with optimized AV delays. Devices were subsequently set to VVIR with matched heart rates and after 20 minutes the CO measurement was repeated. Mean CO of 6.4 ± 1.8 L/min was significantly higher in DDD/VDD than in VVIR, where it averaged 5.2 ± 1.4 L/min (p

had little effect. Stroke volume and heart rate increases were responsible, with heart rate becoming more dominant over time. There was no significant flow increase to the head, kidneys or legs. Intestinal blood flow (coeliac trunk, SMA, portal vein) was responsible for the increase in cardiac output in the first hour after the meal. The figure shows results from selected multilevel models, adjusted for sex, age and BMI. Aortic flow, stroke volume and heart rate changes compared to rest were significantly different between meal and water ingestions. This was also true for SMA flow but not cerebral, renal or distal aortic flow.