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Background The Fontan circulation challenges the lymphatic system. Increasing production of lymphatic fluid and impeding lymphatic return, increased venous pressure may cause lymphatic dilatation and decrease lymphatic contractility. In-vitro studies have reported a lymphatic diameter-tension curve, with increasing passive stretch affecting the intrinsic contractile properties of each thoracic duct segment. We aimed to describe thoracic duct occlusion pressure and asses if thoracic duct dilation impairs contractility in individuals with a Fontan circulation and lymphatic failure. Methods Central venous pressure and thoracic duct measurements were retrospectively collected from 31 individuals with a Fontan circulation. Thoracic duct occlusion pressure was assessed during a period of external manual compression and used as an indicator of lymphatic vessel contractility. Measurements of pressure were correlated with measurements of the thoracic duct diameter in images obtained by dynamic contrast-enhanced MR lymphangiography. Results The average central venous pressure and average pressure of the thoracic duct were 17 mm Hg. During manual occlusion, the thoracic duct pressure significantly increased to 32 mm Hg. The average thoracic duct diameter was 3.3 mm. Thoracic duct diameter correlated closely with the central venous pressure. The rise in pressure following manual occlusion showed an inverse correlation with the diameter of the thoracic duct. Conclusion Higher central venous pressures are associated with increasing diameters of the thoracic duct. When challenged by manual occlusion, dilated thoracic ducts display a decreased ability to increase pressure. Dilatation and a resulting decreased contractility may partly explain the challenged lymphatic system in individuals with a Fontan circulation.

Patients with atrial septal defects (ASDs) have increased mortality and morbidity. This can only partly be explained by hemodynamic changes caused by the ASD, suggesting additional underlying causes. Patients with an ASD have an increased burden of pathogenic gene variants in ASD-related genes, indicating genetics as an important factor in etiology. Inheritance of genetic variants with high impact can cause ASD in relatives (familial ASD). This study aimed to investigate whether lifelong outcomes were different in patients with familial ASD compared with patients with sporadic ASD. We used health registries and a nationwide cohort of 2,151 patients with ASD to compare the incidences of atrial fibrillation or flutter (together abbreviated as AF), heart failure, and mortality between patients with familial and sporadic ASD using Cox proportional hazard ratio and Fine and Gray analysis. Patients with familial ASD experienced AF and heart failure earlier in life than patients with sporadic ASD, with hazard ratios of 1.6 and 1.7, respectively. Subdistribution hazard ratios showed an increased risk of AF and heart failure in patients with familial ASD compared with patients with sporadic ASDs (2.3 and 3.1, respectively). Our results suggest that genetic variants with high impact may influence the outcomes of patients with ASD. In conclusion, patients with familial ASD have an increased risk and an earlier onset of AF and heart failure compared with patients with sporadic ASD, hence clinical awareness of arrhythmias and heart failure in patients with familial ASD may lead to timely treatment.

Objectives. Readmission rates following open cardiac surgery are high, affecting patients and the cost of care. This study aimed to investigate the effect of early additional follow-up after open cardiac surgery when 5th-year medical students conducted follow-ups under the supervision of physicians. The primary endpoint was unplanned cardiac-related readmissions within one year. The secondary outcomes were the detection of impending complications and health-related quality of life (HRQOL). Methods. Patients undergoing open cardiac surgery were prospectively included. For intervention, additional follow-up visits, including point-of-care ultrasound, were conducted by supervised 5th-year medical students on postoperative days 3, 14 and 25. Unplanned cardiac-related readmissions, including emergency department visits, were registered within the first year of surgery. Danish National Health Survey 2010 questionnaire was used for HRQOL. In standard follow-up, all patients were seen 4-6 weeks postoperative. Results. For data analysis, 100 of 124 patients in the intervention group and 319 of 335 patients in the control group were included. The 1-year unplanned readmission rates did not differ; 32% and 30% in the intervention and control groups, respectively (p = 0.71). After discharge, 1% of patients underwent pericardiocentesis. The additional follow-up initiated scheduled drainage, contrary to more unscheduled/acute drainages in the control group. Pleurocentesis was more common in the intervention group (17% (n = 17) vs 8% (n = 25), p = 0.01) and performed earlier. There was no difference between groups on HRQOL. Conclusion. Supervised student-led follow-up of newly cardiac-operated patients did not alter readmission rates or HRQOL but may detect complications earlier and initiate non-emergent treatment of complications.

BACKGROUND: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks.METHODS: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis).RESULTS: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879).CONCLUSIONS: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.

Objectives: Small, unrepaired atrial septal defects are considered a benign lesion with good prognosis. Recently, clinical and register-based studies discovered increased long-term mortality and morbidity. The nature of these findings is not fully understood. Therefore, MRI was performed to evaluate cardiac function at rest and during exercise. Methods: Adults with open or spontaneously closed atrial septal defects and healthy, matched controls underwent MRI for evaluation of cardiac chamber volume. Quantitative flow scans measured blood flow in the ascending aorta and the proximal pulmonary artery at rest and during increasing supine exercise. Results: In total, 15 open defects (39 ± 11 years) and 15 matched controls (38 ± 12 years) were included, along with 20 spontaneously closed (36 ± 13 years) and 20 controls (36 ± 11 years). Cardiac chamber volumes and flow measurements at rest were comparable between groups, as were heart rates and workloads during exercise. At maximal exercise, open defects reached 31% lower cardiac index and had 38% higher retrograde flow in the pulmonary artery than their controls, p < 0.01. Shunt ratio remained unchanged during exercise, 1.2 ± 0.2. Closed defects reached 18% lower cardiac index, p = 0.02, with comparable pulmonary retrograde flow. Maximal cardiac index was inversely correlated with increasing age for patients only. Conclusion: Adults with a small, open or spontaneously closed atrial septal defects exhibit markedly lower exercise capacity compared with healthy peers. Moreover, open defects exhibit higher retrograde flows with increasing exercise. Finally, increasing age is related to poorer results in patients but not healthy controls. Longitudinal studies are necessary in order to determine potential accelerated worsening of physical capacity along with age-related changes in patients.

Ventricular septal defects (VSDs) have recently demonstrated poorer functional outcome with disrupted ventricular contractility during exercise in young patients. It is not known whether this will change with age. Therefore, echocardiography was performed in older patients with congenital VSDs, either surgically closed or unrepaired and all without Eisenmenger physiology, to compare functional outcomes with healthy peers. Transthoracic echocardiography was performed at rest and during supine bicycle exercise, with tissue velocity Doppler for assessment of primary end points: isovolumetric acceleration and systolic velocities. In total, 30 surgically closed VSDs (51 ± 8 years) with 30 healthy controls (52 ± 9 years) and 30 unrepaired VSDs (55 ± 12 years) with 30 matched controls (55 ± 10 years) were included. Surgical patients displayed lower right ventricular (RV) systolic and early diastolic-filling velocities compared with controls, p

Objectives:The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.Methods:Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.Results:Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.Conclusion:Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

Background Despite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD. Methods and Results Thirty‐eight corrected patients with isolated secundum ASD and 19 age‐matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O 2 /kg per minute, controls 35.2±7.5 mL O 2 /kg per minute, P =0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P =0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P =0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P =0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response. Conclusions Patients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long‐term risk of atrial fibrillation. Registration Information clinicaltrials.gov. Identifier: NCT03565471.

Background Congenital ventricular septal defects (VSDs) are considered to have benign long‐term outcome when treated correctly in childhood. However, abnormal parameters are described in younger adults, including impaired heart rate variability (HRV). It is not known whether such abnormalities will deteriorate with age. Therefore, HRV and cardiac events, such as premature ventricular contraction, were evaluated in patients aged >40 years with congenital VSDs and compared with healthy peers. Methods and Results A total of 30 surgically closed VSDs (51±8 years, repair at median age 6.3 years with total range 1.4–54 years) with 30 healthy controls (52±9 years) and 30 small, unrepaired VSDs (55±12 years) with 30 controls (55±10 years) were all equipped with a Holter monitor for 24 hours. Compared with healthy peers, surgically closed patients had lower SD of the normal‐to‐normal (NN) interbeat interval (129±37 versus 168±38 ms; P P P 200 events) was registered in 57% of surgical patients compared with 3% of controls ( P P Conclusions Adults aged >40 with congenital VSDs demonstrate impaired HRV, mainly among surgically closed VSDs. More than half demonstrated a high number of premature ventricular contractions. These novel findings could indicate long‐term cardiovascular disturbances. This necessitates continuous follow‐up of VSDs throughout adulthood.

Background Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnormalities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. Methods and Results Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group ( P =0.033 and P =0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. Conclusions Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding patterns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03871881.

Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow‐up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age. Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P P P P P =0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers. Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age—and increased most in patients with operated VSDs—compared with previous findings in younger patients. Results warrant continuous follow‐up for these simple defects.

Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel walls, and also to aortic valve leaflets. Stentless aortic heart valves are known to possess several hemodynamic benefits such as a larger effective orifice area and a lower aortic transvalvular pressure difference compared to their stented counterparts. To date, turbulence analysis downstream of a stentless valve prosthesis has been investigated exclusively indirectly, using magnetic resonance imaging or in animal settings only. The study aim was to investigate turbulence using direct Doppler ultrasonography measurements in subcoronary stentless and stented valves in human subjects.Either stented pericardial valve prostheses (Mitroflow) or stentless valve prostheses (Solo) were implanted in 15 patients in a randomized fashion. Following surgery, blood velocity was measured in the cross-sectional area downstream of the valves using 10 MHz ultrasonic probes connected to dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) values were calculated, as well as two-dimensional maps of the turbulence distribution. Preoperative and perioperative data were collected prospectively, and postoperative data retrospectively, from hospital records.The median follow up was 1,624 days. No differences were found in perioperative or postoperative clinical data. Implantation of the Mitroflow valve was significantly faster than that of the Solo valve (p0.05). Neither was any difference found in the mean or max RNS between the two valve groups. However, the turbulence profiles showed a large variation in the Solo valve compared to the more uniform profiles of the Mitroflow valve.Comparable turbulent flow values were found between the two valve types, although the Solo group exhibited a large variation in turbulence profiles. As no clear clinical advantages were shown to exist for stentless valves, a normal stented valve should be the first choice in most cases.

Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4 ± 4.9% of control in the presence of 20 nmol l(-1) nifedipine. Transcripts for the L-type calcium channel gene CACNA1C were consistently detected from human thoracic duct samples examined and the CaV1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics ex vivo were highly sensitive to nifedipine, this was not apparent in vivo when nifedipine was compared to placebo in a randomized, double-blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine in vitro but that care must be taken when extrapolating in vitro observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.

The preservation of aortic root dynamics is considered important for the durability of aortic valve bioprostheses. Stentless heart valves are believed to support physiologic biomechanics. To date, dynamic analysis has been limited to the full root prosthesis, and exclusively in the radial direction. The study aim was to investigate and compare the radial and longitudinal aortic root distensibilities of subcoronary stentless valves, and of stented and native pig valves.Stented pericardial (Mitroflow) or stentless (Solo, Toronto SPV) valve prostheses, or native porcine valves, were investigated in 32 pigs. Postoperatively, 12 sonomicrometry crystals were placed on the aortic root in order to measure aortic root distensibility, in both radial and longitudinal directions.Sonomicrometry data were obtained from 23 pigs (72%). At the annular level, the native and Solo valves were significantly more distensible in a radial direction than the Mitroflow valve (p = 0.04). However, at the level of the sinotubular junction (STJ), commissures and aorta, the native valve was significantly more distensible than all of the artificial valves (p = 0.006, p = 0.006, and p = 0.02, respectively). The Solo valve exhibited less longitudinal distensibility than the Toronto SPV and Mitroflow valves. The Toronto SPV initiated a radial expansion at the STJ significantly later in the cardiac cycle than did both the Solo and native valves (p = 0.03), but showed no difference compared to the Mitroflow valve. Longitudinal expansion between the annulus and the STJ started significantly earlier for the Solo valve than for both the Toronto SPV (p = 0.03) and Mitroflow (p = 0.02) valves.The Solo valve proved to be superior in maintaining annular distensibility immediately following implantation when compared to the Mitroflow valve. The Solo valve did not, however, preserve longitudinal distensibility as well as the other investigated valves. Finally, the Solo valve appeared to provide a more physiologic aortic root expansion pattern than its prosthetic counterparts.

Estimates of the prevalence of congenital heart defects (CHD) have been published over many years and from many regions. As they are based on different definitions of which cases to include in the CHD prevalence, published prevalence estimates vary substantially. With the increasing use of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data on CHD may be used: etiology, planning of treatment, or obtain information on outcome, including mortality. For etiology studies, it is important to include terminations of pregnancy as well as all births with CHD. For mortality studies in live births, inclusion of preterm born infants with PDA will increase overall mortality of CHD. The Danish Register of Congenital Heart Disease is based on hospital discharge diagnoses and diagnoses from outpatient visits. To increase the validity of these data, extensive data cleaning has been carried out based on record review and knowledge on the discharge coding practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD.

Abnormal flow conditions across aortic bioprosthetic valves may result in degenerative processes. Thus, it is important to implant biological valve prostheses with velocity profiles similar to those of native valves. The study aim was to compare blood velocity and velocity gradient profiles downstream of stented and stentless aortic valves implanted in pigs, and in native porcine valves.Stented valve prostheses (Mitroflow, n = 7) or stentless valve prostheses (Solo, n = 5 or Toronto SPV, n = 7) were implanted into pigs; the native valve was retained in eight animals. After weaning the animals from cardiopulmonary bypass, cardiac magnetic resonance imaging was performed to determine the blood velocities and velocity gradient profiles.The native valves had a significantly lower peak velocity (92 +/- 26 cm/s) than the artificial valves (Solo: 247 +/- 107 cm/s; Toronto: 252 +/- 41 cm/s; Mitroflow: 229 +/- 18 cm/s). The native valves exhibited a flat velocity profile during systole, whereas the Solo valve, and especially the Toronto SPV valve, displayed more parabola-shaped velocity profiles; velocity profiles downstream of the Mitroflow valve exhibited a flat shape. The native valves had a lower mean velocity gradient at peak systole (p0.0001). The velocity gradient percentage above mean was lowest for the native valve (0.14 +/- 0.11; p0.0001), while the Mitroflow valve had a percentage of 0.57 +/- 0.09, which was lower than the Solo valve (0.69 +/- 0.12; p = 0.074), and significantly lower than the Toronto valve (0.70 +/- 0.08; p = 0.015). All valves displayed high velocity gradients adjacent to the aortic wall; in particular, the Toronto SPV which also had high velocity gradients at the center of the vessel.All of the artificial valves tested had a significantly higher mean velocity gradient and peak velocity than the native valves. However, the Mitroflow had a mean velocity and a velocity gradient percentage lower than the two stentless valves. The Solo and Mitroflow valves displayed velocity profiles most like native valves, while the Toronto valve had a more irregular asymmetric velocity profile.

Previously, the Mustard operation was the preferred surgical technique in patients with transposition of the great arteries. After this procedure the anatomical right ventricle remains the systemic ventricle, which entails long-term complications, especially heart failure. The Mustard-operated patients are now adults, and pregnancy has become an important issue. We assessed pregnancy and delivery data in a complete cohort of female patients who had previously undergone a Mustard procedure at Aarhus Hospital in the 1971-1991 period. The women giving birth were compared with those who did not.Information on diagnosis, procedure, functional status, pregnancy, delivery and congenital heart disease in the off-spring were found in registers (The National Register of Health, The National Birth Register) and in medical records. Questionnaires were mailed to the 16 surviving women over 15 years of age.Four women gave birth to nine children. Two women temporally had heart symptoms during pregnancy and delivery, but this caused no objective changes. The women who had children were older than those who did not. None of the children had congenital heart disease nor were they small for their gestational age.Pregnancy and delivery are well-tolerated in the vast majority of Mustard-operated women with no deterioration in functional class during or after pregnancy and delivery.