Publications by authors named "Vibeke E Hjortdal"

103 Publications

Long-term neurodevelopmental effects of intraoperative blood pressure during surgical closure of a septal defect in infancy or early childhood.

Cardiol Young 2021 Apr 12:1-7. Epub 2021 Apr 12.

Department of Anesthesiology, Centre of Head and Orthopaedics, Copenhagen University Hospital, Copenhagen, Denmark.

Background: Many children born with congenital heart defects are faced with cognitive deficits and psychological challenges later in life. The mechanisms behind are suggested to be multifactorial and are explained as an interplay between innate and modifiable risk factors. The aim was to assess whether there is a relationship between mean arterial pressure during surgery of a septal defect in infancy or early childhood and intelligence quotient scores in adulthood.

Methods: In a retrospective study, patients were included if they underwent surgical closure of a ventricular septal defect or an atrial septal defect in childhood between 1988 and 2002. Every patient completed an intelligence assessment upon inclusion, 14-27 years after surgery, using the Wechsler Adult Intelligence Scale Version IV.

Results: A total of 58 patients met the eligibility criteria and were included in the analyses. No statistically significant correlation was found between blood pressure during cardiopulmonary bypass and intelligence quotient scores in adulthood (r = 0.138; 95% CI-0.133-0.389). Although amongst patients with mean arterial pressure < 40 mmHg during cardiopulmonary bypass, intelligence quotient scores were significantly lower (91.4; 95% CI 86.9-95.9) compared to those with mean arterial pressure > 40 mmHg (99.8; 95% CI 94.7-104.9).

Conclusions: Mean arterial pressure during surgery of ventricular septal defects or atrial septal defects in childhood does not correlate linearly with intelligence quotient scores in adulthood. Although there may exist a specific cut-off value at which low blood pressure becomes harmful. Larger studies are warranted in order to confirm this, as it holds the potential of partly relieving CHD patients of their cognitive deficits.
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http://dx.doi.org/10.1017/S1047951121001414DOI Listing
April 2021

Radiofrequency catheter ablation in 246 children with supraventricular tachyarrhythmia.

Dan Med J 2021 Mar 24;68(4). Epub 2021 Mar 24.

Introduction: Radiofrequency catheter ablation (RFA) is the treatment of choice for a variety of cardiac arrhythmias in adults. RFA is considered effective and is associated with few complications. We aimed to review the characteristics and outcomes of invasive electrophysiological study (EPS) and RFA in children with supraventricular tachyarrhythmia.

Methods: Consecutive patients younger than 16 years of age undergoing EPS and possible RFA from January 2009 to September 2018 at Aarhus University Hospital (uptake three million people) were reviewed retrospectively. Procedural and outcome data were collected from patient charts and from the Danish Ablation Database. Numbers (%) or median (range) are reported.

Results: A total of 304 patients (148 girls) underwent EPS (352 procedures). RFA was performed in 246 patients (279 procedures), aged 13 (1-15) years and weighing 46 (6-99) kg. Treatment success was achieved in 195 (79%) of the initial procedures. Using more than one procedure, 227 (92%) patients were free from arrhythmia after 89 (26-143) months of follow-up. The procedure time was 60 (22-222) min. and ablation time 2 (1-23) min. Major complications occurred in two cases. One patient developed transient superior vena cava syndrome and one patient developed an atrioventricular block requiring pacemaker implantation.

Conclusions: RFA may be performed in children with a high success rate and a low but not negligible risk of complications.

Funding: none.

Trial Registration: Approval was obtained from the Danish Data Protection Agency (1-16-02-430-13).
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March 2021

Partial Anomalous Pulmonary Venous Connection: Forty-Six Years of Follow-Up.

World J Pediatr Congenit Heart Surg 2021 Jan;12(1):70-75

Department of Cardiothoracic Surgery, 53146Aarhus University Hospital, Aarhus, Denmark.

Background: Surgical repair of partial anomalous pulmonary venous connection (PAPVC) may disturb the electrical conduction in the atria. This study documents long-term outcomes, including the late occurrence of atrial tachyarrhythmia and bradyarrhythmia.

Methods: This retrospective study covers all PAPVC operations at Aarhus University Hospital between 1970 and 2010. Outcome measures were arrhythmias, sinus node disease, pacemaker implantation, pathway stenosis (pulmonary vein(s), intra-atrial pathway, and/or superior vena cava), and mortality. Data were collected from databases, surgical protocols, and hospital records until May 2018.

Results: A total of 83 patients were included with a postoperative follow-up period up to 46 years. Average age at follow-up was 43 ± 21 years. During follow-up, new-onset atrial fibrillation or atrial flutter appeared in four patients (5%). Sinus node disease was present in nine patients (11%). A permanent pacemaker was implanted in seven patients (8%) at an average of 12.7 years after surgery. Pulmonary venous and/or superior vena cava obstruction was seen in five patients (6%). Stenosis was most prevalent in the two-patch technique, and arrhythmia was most prevalent in the single-patch technique. Sixty-seven (81%) of 83 patients had neither bradyarrhythmias nor tachyarrhythmias or pacemaker need.

Conclusions: This study contributes important long-term data concerning the course of patients who have undergone repair of PAPVC. It confirms that PAPVC can be operated with low postoperative morbidity. However, late-onset stenosis, bradyarrhythmias and tachyarrhythmias, and need for pacemaker call for continued follow-up.
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http://dx.doi.org/10.1177/2150135120960482DOI Listing
January 2021

Reply.

J Pediatr 2021 03 27;230:273-274. Epub 2020 Nov 27.

Perinatal Epidemiology Research Unit, Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1016/j.jpeds.2020.11.057DOI Listing
March 2021

Congenital Heart Defects and the Risk of Spontaneous Preterm Birth.

J Pediatr 2021 02 24;229:168-174.e5. Epub 2020 Sep 24.

Perinatal Epidemiology Research Unit, Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.

Objectives: To estimate the association between major types of congenital heart defects (CHD) and spontaneous preterm birth, and to assess the potential underlying mechanisms.

Study Design: This nationwide, registry-based study included a cohort of all singleton pregnancies in Denmark from 1997 to 2013. The association between CHD and spontaneous preterm birth was estimated by multivariable Cox regression, adjusted for potential confounders. The following potential mechanisms were examined: maternal genetics (sibling analyses), polyhydramnios, preterm prelabor rupture of membranes, preeclampsia, and indicators of fetal and placental growth.

Results: The study included 1 040 474 births. Compared with the general population, CHD was associated with an increased risk of spontaneous preterm birth, adjusted hazard ratio 2.1 (95% CI, 1.9-2.4). Several subtypes were associated with increased risks, including pulmonary stenosis combined with a septal defect, 5.2 (95% CI, 3.7-7.5); pulmonary stenosis or atresia, 3.1 (95% CI, 2.4-4.1); tetralogy of Fallot 2.5 (95% CI, 1.6-3.8); coarctation or interrupted aortic arch 2.2 (95% CI, 1.5-3.2); and hypoplastic left heart syndrome, 2.0 (95% CI, 1.0-4.1). Overall, preterm prelabor rupture of membranes mediated more than one-half of the association. Maternal genetics, polyhydramnios, or indicators of fetal or placental growth did not explain the reported associations.

Conclusions: CHD, especially right ventricular outflow tract obstructions, were associated with an increased risk of spontaneous preterm birth. The risk was carried by the CHD and not by maternal genetics. Moreover, preterm prelabor rupture of membranes was identified as a potential underlying mechanism.
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http://dx.doi.org/10.1016/j.jpeds.2020.09.059DOI Listing
February 2021

Functional Capacity Past Age 40 in Patients With Congenital Ventricular Septal Defects.

J Am Heart Assoc 2020 10 23;9(19):e015956. Epub 2020 Sep 23.

Department of Clinical Medicine Aarhus University Aarhus N Denmark.

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, <0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, <0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups (<0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, <0.01) but similar in patients with unrepaired VSDs and control participants (=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.
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http://dx.doi.org/10.1161/JAHA.120.015956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792429PMC
October 2020

Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: A cohort study.

Early Hum Dev 2020 10 1;149:105142. Epub 2020 Aug 1.

Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark; Department of Pediatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark. Electronic address:

Background: The evaluation of the patent ductus arteriosus (PDA) in the very premature neonate is a challenge. Echocardiography provides an interpretation of the hemodynamic condition. It is however, only a snapshot. Biomarkers may represent a physiological response to the hemodynamic alterations brought on by the PDA and may add to the identification of the clinical significant PDA.

Aim: To investigate the association between mid regional proadrenomodulin (MR-proADM), N-terminal pro b-type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET1) and copeptin and echocardiographic measures of PDA.

Study Design: Cohort study with echocardiography performed on day 3 and 6. Blood samples from day 3.

Subject: 139 consecutive neonates born at a gestational age <32 weeks.

Outcome Measures: The main outcomes were presence of a PDA day 3 and 6, PDA diameter, left atrium to aorta ratio (LA:Ao-ratio), and descending aorta diastolic flow (DADF).

Results: Adjusted plasma levels of all investigated biomarkers, except CT-proET1, were found to be associated with both PDA diameter and LA:Ao-ratio, and also the presence of a large PDA. CT-proET1 and copeptin was found to be associated with abnormal DADF. Using pre-specified cut-off values NT-proBNP and MR-proANP day 3 seemed to be of value in identifying a large PDA day 3 and 6 in very preterm neonates.

Conclusion: Among the investigated biomarkers NT-proBNP and MR-proANP performed best in relation to echocardiographic markers of PDA severity in very preterm neonates.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105142DOI Listing
October 2020

Evaluating Vitamin D levels in Rheumatic Heart Disease patients and matched controls: A case-control study from Nepal.

PLoS One 2020 21;15(8):e0237924. Epub 2020 Aug 21.

Department of Cardiothoracic & Vascular Surgery, Aarhus University Hospital, Skejby, Aarhus, Denmark.

Background: Diagnosis and treatment for Rheumatic Heart Disease (RHD) is inaccessible for many of the 33 million people in low and middle income countries living with this disease. More knowledge about risk factors and pathophysiologic mechanisms involved is needed in order to prevent disease and optimize treatment. This study investigated risk factors in a Nepalese population, with a special focus on Vitamin D deficiency because of its immunomodulatory effects.

Methods: Ninety-nine patients with confirmed RHD diagnosis and 97 matched, cardiac-healthy controls selected by echocardiography were recruited from hospitals in the Central and Western region of Nepal. Serum 25(OH)D concentrations were assessed using dried blood spots and anthropometric values measured to evaluate nutritional status. Conditional logistic regression analysis was used to define association between vitamin D deficiency and RHD.

Results: The mean age of RHD patients was 31 years (range 9-70) and for healthy controls 32 years (range 9-65), with a 4:1 female to male ratio. Vitamin D levels were lower than expected in both RDH and controls. RHD patients had lower vitamin D levels than controls with a mean s-25(OH)D concentration of 39 nmol/l (range 8.7-89.4) compared with controls 45 nmol/l (range 14.5-86.7) (p-value = 0.02). People with Vitamin D insufficiency had a higher risk (OR = 2.59; 95% CI: 1.04-6.50) of also having RHD compared to people with Vitamin D concentrations >50 nmol/l. Body mass index was significantly lower in RHD patients (22.6; 95% CI, 21.5-23.2) compared to controls (24.2; 95% CI, 23.3-25.1).

Conclusion: RHD patients in Nepal have lower Vitamin D levels and overall poor nutritional status compared to the non-RHD controls. Longitudinal studies are needed to explore the causality between RHD and vitamin D level. Future research is also recommended among Nepali general population to confirm the low level of vitamin D as reported in our control group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237924PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444549PMC
October 2020

No Added Neuroprotective Effect of Remote Ischemic Postconditioning and Therapeutic Hypothermia After Mild Hypoxia-Ischemia in a Piglet Model.

Front Pediatr 2020 26;8:299. Epub 2020 Jun 26.

Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.

Hypoxic ischemic encephalopathy (HIE) is a major cause of death and disability in children worldwide. Apart from supportive care, the only established treatment for HIE is therapeutic hypothermia (TH). As TH is only partly neuroprotective, there is a need for additional therapies. Intermittent periods of limb ischemia, called remote ischemic postconditioning (RIPC), have been shown to be neuroprotective after HIE in rats and piglets. However, it is unknown whether RIPC adds to the effect of TH. We tested the neuroprotective effect of RIPC with TH compared to TH alone using magnetic resonance imaging and spectroscopy (MRI/MRS) in a piglet HIE model. Thirty-two male and female piglets were subjected to 45-min global hypoxia-ischemia (HI). Twenty-six animals were randomized to TH or RIPC plus TH; six animals received supportive care only. TH was induced through whole-body cooling. RIPC was induced 1 h after HI by four cycles of 5 min of ischemia and 5 min of reperfusion in both hind limbs. Primary outcome was Lac/NAA ratio at 24 h measured by MRS. Secondary outcomes were NAA/Cr, diffusion-weighted imaging (DWI), arterial spin labeling, aEGG score, and blood oxygen dependent (BOLD) signal measured by MRI/MRS at 6, 12, and 24 h after the hypoxic-ischemic insult. All groups were subjected to a comparable but mild insult. No difference was found between the two intervention groups in Lac/NAA ratio, NAA/Cr ratio, DWI, arterial spin labeling, or BOLD signal. NAA/Cr ratio at 24 h was higher in the two intervention groups compared to supportive care only. There was no difference in aEEG score between the three groups. Treatment with RIPC resulted in no additional neuroprotection when combined with TH. However, insult severity was mild and only evaluated at 24 h after HI with a short MRS echo time. In future studies more subtle neurological effects may be detected with increased MRS echo time and post mortem investigations, such as brain histology. Thus, the possible neuroprotective effect of RIPC needs further evaluation.
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http://dx.doi.org/10.3389/fped.2020.00299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333529PMC
June 2020

Pacemaker and conduction disturbances in patients with atrial septal defect.

Cardiol Young 2020 Jul 5;30(7):980-985. Epub 2020 Jun 5.

Department of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.

Objective: To determine the prevalence of pacemaker and conduction disturbances in patients with atrial septal defects.

Design: All patients with an atrial septal defect born before 1994 were identified in the Danish National Patient Registry, and 297 patients were analysed for atrioventricular block, bradycardia, right bundle branch block, left anterior fascicular block, left posterior fascicular block, pacemaker, and mortality. Our results were compared with pre-existing data from a healthy background population. Further, outcomes were compared between patients with open atrial septal defects and atrial septal defects closed by surgery or transcatheter.

Results: Most frequent findings were incomplete right bundle branch block (40.1%), left anterior fascicular block (3.7%), atrioventricular block (3.7%), and pacemaker (3.7%). Average age at pacemaker implantation was 32 years. Patients with defects closed surgically or by transcatheter had an increased prevalence of atrioventricular block (p < 0.01), incomplete right bundle branch block (p < 0.01), and left anterior fascicular block (p = 0.02) when compared to patients with unclosed atrial septal defects. At age above 25 years, there was a considerably higher prevalence of atrioventricular block (9.4% versus 0.1%) and complete right bundle branch block (1.9% versus 0.4%) when compared to the background cohorts.

Conclusions: Patients with atrial septal defects have a considerably higher prevalence of conduction abnormalities when compared to the background population. Patients with surgically or transcatheter closed atrial septal defects demonstrated a higher demand for pacemaker and a higher prevalence of atrioventricular block, incomplete right bundle branch block, and left anterior fascicular block when compared to patients with unclosed atrial septal defects.
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http://dx.doi.org/10.1017/S1047951120001365DOI Listing
July 2020

Increasing carbohydrate oxidation improves contractile reserves and prevents hypertrophy in porcine right heart failure.

Sci Rep 2020 05 18;10(1):8158. Epub 2020 May 18.

Comparative Medicine Lab, Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

In heart failure, myocardial overload causes vast metabolic changes that impair cardiac energy production and contribute to deterioration of contractile function. However, metabolic therapy is not used in heart failure care. We aimed to investigate the interplay between cardiac function and myocardial carbohydrate metabolism in a large animal heart failure model. Using magnetic resonance spectroscopy with hyperpolarized pyruvate and magnetic resonance imaging at rest and during pharmacological stress, we investigated the in-vivo cardiac pyruvate metabolism and contractility in a porcine model of chronic pulmonary insufficiency causing right ventricular volume overload. To assess if increasing the carbohydrate metabolic reserve improves the contractile reserve, a group of animals were fed dichloroacetate, an activator of pyruvate oxidation. Volume overload caused heart failure with decreased pyruvate dehydrogenase flux and poor ejection fraction reserve. The animals treated with dichloroacetate had a larger contractile response to dobutamine stress than non-treated animals. Further, dichloroacetate prevented myocardial hypertrophy. The in-vivo metabolic data were validated by mitochondrial respirometry, enzyme activity assays and gene expression analyses. Our results show that pyruvate dehydrogenase kinase inhibition improves the contractile reserve and decreases hypertrophy by augmenting carbohydrate metabolism in porcine heart failure. The approach is promising for metabolic heart failure therapy.
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http://dx.doi.org/10.1038/s41598-020-65098-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235019PMC
May 2020

Increasing carbohydrate oxidation improves contractile reserves and prevents hypertrophy in porcine right heart failure.

Sci Rep 2020 05 18;10(1):8158. Epub 2020 May 18.

Comparative Medicine Lab, Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

In heart failure, myocardial overload causes vast metabolic changes that impair cardiac energy production and contribute to deterioration of contractile function. However, metabolic therapy is not used in heart failure care. We aimed to investigate the interplay between cardiac function and myocardial carbohydrate metabolism in a large animal heart failure model. Using magnetic resonance spectroscopy with hyperpolarized pyruvate and magnetic resonance imaging at rest and during pharmacological stress, we investigated the in-vivo cardiac pyruvate metabolism and contractility in a porcine model of chronic pulmonary insufficiency causing right ventricular volume overload. To assess if increasing the carbohydrate metabolic reserve improves the contractile reserve, a group of animals were fed dichloroacetate, an activator of pyruvate oxidation. Volume overload caused heart failure with decreased pyruvate dehydrogenase flux and poor ejection fraction reserve. The animals treated with dichloroacetate had a larger contractile response to dobutamine stress than non-treated animals. Further, dichloroacetate prevented myocardial hypertrophy. The in-vivo metabolic data were validated by mitochondrial respirometry, enzyme activity assays and gene expression analyses. Our results show that pyruvate dehydrogenase kinase inhibition improves the contractile reserve and decreases hypertrophy by augmenting carbohydrate metabolism in porcine heart failure. The approach is promising for metabolic heart failure therapy.
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http://dx.doi.org/10.1038/s41598-020-65098-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235019PMC
May 2020

Disappearance of the shunt and lower cardiac index during exercise in small, unrepaired ventricular septal defects.

Cardiol Young 2020 Apr 25;30(4):526-532. Epub 2020 Mar 25.

Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Blv. 99, DK-8200Aarhus N, Denmark.

Objectives: Clinical studies have revealed decreased exercise capacity in adults with small, unrepaired ventricular septal defects. Increasing shunt ratio and growing incompetence of the aortic and pulmonary valve with retrograde flow during exercise have been proposed as reasons for the previously found reduced exercise parameters. With MRI, haemodynamic shunt properties were measured during exercise in ventricular septal defects.

Methods: Patients with small, unrepaired ventricular septal defects and healthy peers were examined with MRI during exercise. Quantitative flow scans measured blood flow through ascending aorta and pulmonary artery. Scans were analysed post hoc where cardiac index, retrograde flows, and shunt ratio were determined.

Results: In total, 32 patients (26 ± 6 years) and 28 controls (27 ± 5 years) were included. The shunt ratio was 1.2 ± 0.2 at rest and decreased to 1.0 ± 0.2 at peak exercise, p < 0.01. Aortic cardiac index was lower at peak exercise in patients (7.5 ± 2 L/minute/m2) compared with controls (9.0±2L l/minute/m2), p<0.01. Aortic and pulmonary retrograde flow was larger in patients during exercise, p < 0.01. Positive correlation was demonstrated between aortic cardiac index at peak exercise and previously established exercise capacity for all patients (r = 0.5, p < 0.01).

Conclusions: Small, unrepaired ventricular septal defects revealed declining shunt ratio with increasing exercise and lower aortic cardiac index. Patients demonstrated larger retrograde flow both through the pulmonary artery and the aorta during exercise compared with controls. In conclusion, adults with unrepaired ventricular septal defects redistribute blood flow during exercise probably secondary to a more fixed pulmonary vascular resistance compared with age-matched peers.
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http://dx.doi.org/10.1017/S1047951120000505DOI Listing
April 2020

Tele-rehabilitation and hospital-based cardiac rehabilitation are comparable in increasing patient activation and health literacy: A pilot study.

Eur J Cardiovasc Nurs 2020 06 8;19(5):376-385. Epub 2019 Nov 8.

Centre of Research in Rehabilitation, Aarhus University, Denmark.

Background: Cardiac tele-rehabilitation is defined as using information and communication technology to support rehabilitation services. However, it requires a high level of patient activation and health literacy; this has not yet been explored.

Aims: The purpose of this study was to evaluate patient activation and health literacy in tele-rehabilitation compared to hospital-based cardiac rehabilitation.

Methods: We conducted a pilot study in patients with ischaemic or heart valve disease. In a non-randomised design, 24 patients attended a 12-week tele-rehabilitation programme, and 53 matched controls a 12-week hospital-based cardiac rehabilitation programme. The primary outcome was patient activation, which was assessed using the Patient Activation Measure before the intervention, at the end of the intervention and at follow-up six months after the intervention. The secondary outcome was health literacy, assessed using three dimensions from the Health Literacy Questionnaire before rehabilitation and at six-month follow-up: actively manage my health (HLQ3), ability to engage with healthcare providers (HLQ6) and understanding health information (HLQ9).

Results: Patient activation improved similarly in tele-rehabilitation and hospital-based cardiac rehabilitation at all time points. Six months after the intervention, patients in tele-rehabilitation significantly improved on the dimension HLQ6 compared to patients in hospital-based cardiac rehabilitation. No significant between-group differences were found in HLQ3 or HLQ9.

Conclusion: Tele-rehabilitation and hospital-based cardiac rehabilitation seemed to be equally successful in improving patient activation and health literacy. Tele-rehabilitation should be further tested in a randomised controlled trial, with a focus on whether patient levels of education and self-management at the initiation of rehabilitation are decisive factors for tele-rehabilitation participation.
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http://dx.doi.org/10.1177/1474515119885325DOI Listing
June 2020

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study.

Eur J Cardiothorac Surg 2020 03;57(3):574-580

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark.

Objectives: Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated.

Methods: Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise.

Results: In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity.

Conclusions: Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.
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http://dx.doi.org/10.1093/ejcts/ezz278DOI Listing
March 2020

Resolving the natural myocardial remodelling brought upon by cardiac contraction; a porcine ex-vivo cardiovascular magnetic resonance study of the left and right ventricle.

J Cardiovasc Magn Reson 2019 07 1;21(1):35. Epub 2019 Jul 1.

Department of Cardiothoracic & Vascular Surgery, Aarhus University Hospital, Skejby, Denmark.

Background: The three-dimensional rearrangement of the right ventricular (RV) myocardium during cardiac deformation is unknown. Previous in-vivo studies have shown that myocardial left ventricular (LV) deformation is driven by rearrangement of aggregations of cardiomyocytes that can be characterised by changes in the so-called E3-angle. Ex-vivo imaging offers superior spatial resolution compared with in-vivo measurements, and can thus provide novel insight into the deformation of the myocardial microstructure in both ventricles. This study sought to describe the dynamic changes of the orientations of the cardiomyocytes in both ventricles brought upon by cardiac contraction, with particular interest in the thin-walled RV, which has not previously been described in terms of its micro-architecture.

Methods: The hearts of 14 healthy 20 kg swine were excised and preserved in either a relaxed state or a contracted state. Myocardial architecture was assessed and compared between the two contractional states by quantification of the helical, transmural and E3-angles of the cardiomyocytes using high-resolution diffusion tensor imaging.

Results: The differences between the two states of contraction were most pronounced in the endocardium where the E3-angle decreased from 78.6° to 24.8° in the LV and from 82.6° to 68.6° in the RV. No significant change in neither the helical nor the transmural angle was found in the cardiomyocytes of the RV. In the endocardium of the LV, however, the helical angle increased from 35.4° to 47.8° and the transmural angle increased from 3.1° to 10.4°.

Conclusion: The entire myocardium rearranges through the cardiac cycle with the change in the orientation of the aggregations of cardiomyocytes being the predominant mediator of myocardial wall thickening. Interestingly, differences also exist between the RV and LV, which helps in the explanation of the different physiological capabilities of the ventricles.
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http://dx.doi.org/10.1186/s12968-019-0547-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600899PMC
July 2019

Small atrial septal defects are associated with psychiatric diagnoses, emotional distress, and lower educational levels.

Congenit Heart Dis 2019 Sep 28;14(5):803-810. Epub 2019 May 28.

Department of Cardiothoracic Surgery, Aarhus University Hospital, Aarhus, Denmark.

Objective: For the first time, we wish to assess the psychiatric burden in adult patients living with small, unrepaired atrial septal defects (ASD) using register-based data, combined with self-reported measures on levels emotional distress and educational status.

Design: A descriptive study using both the unique Danish registries and validated psychiatric questionnaires and scales, including: The Symptom Checklist, Whiteley-7, and Brief Illness Perception Questionnaire.

Patients: Adult patients with small, unrepaired ASD, diagnosed between 1953 and 2011.

Outcome Measures: Number of register-based psychiatric diagnoses. Additionally, symptoms of anxiety, depression, somatization, health anxiety, illness perception, and levels of educational attainment compared to age- and gender-matched individuals from the reference group.

Results: We identified 723 Danish patients with a small, unrepaired ASD. Approximately 17% of the patients eligible for inclusion had one or more psychiatric diagnoses. The most common diagnoses were neurotic, stress-related, and somatoform disorders. A total of 140 patients (mean age 33 years) was included for examination of their mental health using psychiatric questionnaires and scales. Patients with small ASD had higher scores of depression and anxiety when compared to the reference group (0.57 ± 0.67 vs 0.39 ± 0.52; P < .001). Furthermore, patients reported more symptoms of somatization (0.51 ± 0.48 vs 0.34 ± 0.39; P < .001). Finally, a higher percentage of patients with an unrepaired ASD had no education beyond high school when compared to the reference group (33.3% vs 14.3%; P < .001) and a smaller proportion of patients had completed a short-cycle higher education (6.5% vs 16.1%; P = .002).

Conclusion: Patients with a small, unrepaired ASD in adult life have more symptoms of anxiety, depression, and somatization compared to the reference group. Furthermore, fewer patients had no education beyond high school. These results support the guidelines that adults with small ASD warrants regular lifelong follow-up in specialized clinics aware of not only adverse somatic outcome but also rates of depression and anxiety.
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http://dx.doi.org/10.1111/chd.12808DOI Listing
September 2019

Biventricular contractility during exercise in adults with small, unrepaired atrial septal defects.

Echocardiography 2019 06 13;36(6):1139-1144. Epub 2019 May 13.

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus N, Denmark.

Background: Adult patients with a small, unrepaired atrial septal defect (ASD) have higher mortality and increased risk of several comorbidities compared to general population. Further, reduced submaximal and peak exercise capacity was recently demonstrated in these patients. The mechanisms behind these findings remain unexplained and, therefore, biventricular contractility during exercise was assessed by evaluating the force-frequency relationship in the same group of patients.

Methods: Adults patients with a small, unrepaired ASD and healthy age- and gender-matched controls were examined using echocardiography during supine bicycle exercise. Continuous tissue velocity Doppler was used to evaluate isovolumetric acceleration (IVA) and systolic velocities during an incremental workload protocol. All data were analyzed post hoc in a blinded fashion.

Results: We included 30 patients previously diagnosed with a small, unrepaired ASD (mean age 35 years, 63% female) and 25 controls (mean age 34 years, 64% female). Patients had similar values of IVA and systolic velocities at rest when compared with the healthy controls. Further, no differences in IVA was found at peak heart rate for neither the left ventricle (90 ± 39 vs 129 ± 68 cm/s , P = 0.1547) nor the right ventricle (128 ± 56 vs 154 ± 56 cm/s , 0.5691). There were no correlations between peak velocities and the lower exercise capacity previously reported in these patients.

Conclusion: Adult patients with a small, unrepaired ASD have normal biventricular contractility at rest and during exercise when compared with healthy peers. Consequently, the pathophysiological mechanisms behind the impaired exercise capacity previously demonstrated in these patients remains unknown and will be a target for future work.
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http://dx.doi.org/10.1111/echo.14361DOI Listing
June 2019

Acidosis inhibits rhythmic contractions of human thoracic ducts.

Physiol Rep 2019 04;7(8):e14074

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid-base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery. Human thoracic ducts produce complex contractile patterns consisting of tonic rises in tension (isometric myography) or decreases in diameter (isobaric myography) with superimposed phasic contractions. Active tone development decreases substantially (~90% at 30 vs. 7 mmHg) at elevated transmural pressure. Acidosis inhibits spontaneous as well as noradrenaline- and serotonin-induced phasic contractions of human thoracic ducts by 70-90% at extracellular pH 6.8 compared to 7.4 with less pronounced effects observed at pH 7.1. Mean tension responses to noradrenaline and serotonin - averaged over the entire period of agonist exposure - decrease by ~50% at extracellular pH 6.8. Elevating extracellular [K ] from the normal resting level around 4 mmol/L increases overall tension development but reduces phasic activity to a level that is no different between human thoracic duct segments investigated at normal and low extracellular pH. In conclusion, we show that extracellular acidosis inhibits human thoracic duct contractions with more pronounced effects on phasic than tonic contractions. We propose that reduced phasic activity of lymph vessels at low pH attenuates lymph propulsion and increases the risk of edema formation.
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http://dx.doi.org/10.14814/phy2.14074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483936PMC
April 2019

Lifelong burden of small unrepaired atrial septal defect: Results from the Danish National Patient Registry.

Int J Cardiol 2019 05 16;283:101-106. Epub 2019 Feb 16.

Department of Cardiothoracic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Background: Adult patients with small, unrepaired atrial septal defects (ASD) have higher late mortality than the background population. In this nationwide study, we characterize the late natural history of adults with small, unrepaired ASD.

Methods: Using the Danish National Patient Registry, we included all Danish patients, diagnosed between 1953 and 2011 with an unrepaired ASD. Additionally, all patients, aged 18-65, were invited for clinical testing. Patients also completed a general health survey for comparison with the general population.

Results: We identified 723 patients with a small unrepaired ASD. Since the time of diagnosis, 182 patients had died, with an average lifespan of 63 years. The most common cause of death was heart failure. Furthermore, ASD patients had a higher burden of chronic disease than the general population (38.2% vs. 26.9%; p = 0.005), particularly lung disease (3.6% vs. 0.9%; p = 0.008). A total of 153 patients (mean age 32 y) underwent additional testing. On echocardiography an open defect was verified in 19.6% (n = 30) of the patients, of which half subsequently underwent intervention. Interestingly, 6-minute walking distance was markedly reduced (p < 0.0001 compared to normative values) no matter whether the defect was open or closed by echocardiography. Finally, 25.5% of the patients often felt stressed or nervous as compared with 16.3% of the general population (p = 0.004).

Conclusions: Patients with small, unrepaired ASD in adult life have reduced lifespan, more chronic diseases, impaired submaximal exercise capacity, and higher levels of stress than the general population. The current guidelines for intervention and follow-up may need to be reconsidered.
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http://dx.doi.org/10.1016/j.ijcard.2019.02.024DOI Listing
May 2019

Reply to the "Letter to the Editor" by Dr. Lin.

Int J Cardiol 2019 03;278:94

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark; Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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http://dx.doi.org/10.1016/j.ijcard.2018.12.037DOI Listing
March 2019

In-vitro and in-vivo evaluation of a novel bioprosthetic pulmonary valve for use in congenital heart surgery.

J Cardiothorac Surg 2019 Jan 9;14(1). Epub 2019 Jan 9.

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus, Denmark.

Background: Management of congenital malformations of the pulmonary artery and valve can be challenging. The severity often demands early intervention, which is rarely definitive due to the natural growth and multiple surgeries may be required. An artificial valve made entirely from biodegradable materials that will serve as a bioscaffold for host recellularization would be an attractive solution for these patients. Such valves have been experimentally evaluated with various results. In this study, a simple valve design supported by an absorbable proximal stabilization ring is evaluated both in-vitro and in-vivo.

Methods: From a 6.7 × 5.0 cm sheet of CorMatrix® tissue we created the valve as an inverted tubegraft with three sutured commissures. A non-closed ring of LactoSorb® basally supported the valve. The commissure height was 2 cm. Inserted as an interposition graft the valve was tested in an in-vitro model and an acute porcine model. Right ventricular and pulmonary artery pressures were recorded.

Results: The in-vitro testing indicated a proper opening and closure function of valve at physiological simulated hemodynamic conditions. The in-vivo evaluation showed a peak right ventricular pressure of 38 mmHg and a peak pulmonary artery pressure of 27 mmHg and thereby a peak valve gradient of 11 mmHg. The pulmonary pressure wave demonstrated a dicrotic notch indicating competence of the valve.

Conclusion: This new pulmonary valve made entirely from biodegradable tissue worked in an acute setting and displayed a good hemodynamic profile. The valve gradient observed is equal to or superior of today's surgical treatment options.
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http://dx.doi.org/10.1186/s13019-019-0830-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327610PMC
January 2019

Small unrepaired atrial septal defects display impaired exercise capacity compared with healthy peers.

Congenit Heart Dis 2019 May 24;14(3):372-379. Epub 2018 Dec 24.

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark.

Objective: Adult patients with small, unrepaired atrial septal defects have an increased risk of pneumonia, atrial fibrillation, and stroke. Furthermore, they have higher late mortality than the background population. The functional capacity is unknown in these patients. Therefore, our objective was to determine exercise capacity in adult patients diagnosed with an unrepaired atrial septal defect compared to healthy controls.

Design: A cross-sectional study.

Patients: Adult patients with small, unrepaired atrial septal defects, aged 18-65, diagnosed between 1953 and 2011.

Interventions: Cardiopulmonary exercise test was performed using an incremental bicycle test and gas exchange was measured using breath-by-breath technique.

Outcome Measures: Primary outcome was peak oxygen uptake, secondary outcome was maximal workload and ventilatory anaerobic threshold.

Results: We included 32 patients previously diagnosed with a small, unrepaired atrial septal defect and 16 healthy, age- and gender-matched controls (age 36.3 ± 13 years). Patients were divided into two groups based on whether the atrial septal defect was open (age 36.3 ± 11 years) or spontaneously closed (age 36.8 ± 14 years) since time of diagnosis. No differences in demographic characteristics or weekly exercise levels were found. Both patient groups reached lower peak oxygen uptake (open: 31.7 ± 11 mL/kg/min; spontaneously closed: 29.7 ± 6.9 mL/kg/min) compared with controls (42.6 ± 6.1 mL/kg/min; P = .0001). Workload (open: 2.6 ± 1.0 watt/kg; spontaneously closed: 2.5 ± 0.6 watt/kg) and aerobic capacity (open: 21.4 ± 8.7 mL/kg/min; spontaneously closed: 22.5 ± 6.5 mL/kg/min) was also poorer in patients compared to controls (workload: 3.5 ± 0.5 watt/kg; P = .0006, aerobic capacity: 31.3 ± 6.8 mL/kg/min; P = .0007).

Conclusion: Adult patients with a diagnosis of small, unrepaired atrial septal defect have significantly impaired exercise capacity when compared to healthy controls. The impairment was present even if, by the time of assessment, the defect had closed spontaneously. The pathophysiological mechanisms behind the impaired exercise capacity demonstrated in these patients remain unexplained and will be a target for future work.
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http://dx.doi.org/10.1111/chd.12740DOI Listing
May 2019

Heart rate variability is impaired in adults after closure of ventricular septal defect in childhood: A novel finding associated with right bundle branch block.

Int J Cardiol 2019 Jan 25;274:88-92. Epub 2018 Jun 25.

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark; Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Background: Ventricular septal defects (VSDs) generally have benign long-term prognoses, but recent studies have indicated increased pulmonary vascular resistance. A potential tool for monitoring pulmonary artery pressure is heart rate variability, and therefore, the aim of this study was to assess heart rate variability in adults with a surgically repaired or unrepaired VSD.

Methods: In a long-term, follow-up study, three groups were included; VSD-patients operated in early childhood, patients with an open VSD, and controls. For each patient, 24-hour Holter monitoring was performed and heart rate variability was assessed.

Results: In total, 30 participants with a surgically closed VSD, 30 participants with an unrepaired VSD, and 36 controls were included. In the closed VSD group, there was a higher proportion of participants, who had low sNN50 (p = 0.005) and low sNN6% (p = 0.017) than in the other two groups. Similar differences were found when sNN50 was divided into increases and decreases (p = 0.007 and p = 0.005, respectively) as well as sNN6% (p = 0.014 and p = 0.014, respectively). Lastly, there was a higher proportion of patients in the closed VSD group with low rMSSD than in the other two groups (p = 0.005). For the closed VSD group, the proportion of participants with low total sNN50 (p = 0.046) and low total sNN6% (p = 0.046) were higher among participants with a complete right bundle branch block (RBBB) than among participants with no or an incomplete RBBB.

Conclusions: Adults who had surgical VSD closure in early childhood had impaired heart rate variability and, particularly, participants with complete RBBB had lower heart rate variability.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.097DOI Listing
January 2019

Biventricular morphology in adults born with a ventricular septal defect.

Cardiol Young 2018 Dec 30;28(12):1379-1385. Epub 2018 Aug 30.

1Department of Cardiothoracic and Vascular Surgery,Aarhus University Hospital,Aarhus,Denmark.

Ventricular septal defects - large, surgically closed or small, untreated - have demonstrated lower peak exercise capacity compared with healthy controls. The mechanisms behind these findings are not yet fully understood. Therefore, we evaluated biventricular morphology in adults with a ventricular septal defect using MRI. Adults with either childhood surgically closed or small, untreated ventricular septal defects and healthy controls underwent cine MRI for the evaluation of biventricular volumes and quantitative flow scans for measurement of stroke index. Scans were analysed post hoc in a blinded manner. In total, 20 operated patients (22±2 years) and 20 healthy controls (23±2 years) were included, along with 32 patients with small, unrepaired ventricular septal defects (26±6 years) and 28 controls (27±5 years). Operated patients demonstrated larger right ventricular end-diastolic volume index (103±20 ml/m2) compared with their controls (88±16 ml/m2), p=0.01. Heart rate and right ventricular stroke index did not differ between operated patients and controls. Patients with unrepaired ventricular septal defects revealed larger right ventricular end-diastolic volume index (105±17 ml/m2) compared with their controls (88±13 ml/m2), p<0.01. Furthermore, right ventricular stroke index was higher in unrepaired ventricular septal defects (53±12 ml/minute/m2) compared with controls (46±8 ml/minute/m2), p=0.02, with similar heart rates. Both patient groups' right ventricles were visually characterised by abundant coarse trabeculation. Positive correlations were demonstrated between right ventricular end-diastolic volume indices and peak exercise capacity in patients. Left ventricle measurements displayed no differences between groups. In conclusion, altered right ventricular morphology was demonstrated in adults 20 years after surgical ventricular septal defect repair and in adults with small, untreated ventricular septal defects.
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http://dx.doi.org/10.1017/S1047951118001361DOI Listing
December 2018

Telemonitored exercise-based cardiac rehabilitation improves physical capacity and health-related quality of life.

J Telemed Telecare 2020 Jan-Feb;26(1-2):36-44. Epub 2018 Aug 22.

Department of Clinical Medicine, Aarhus University, Denmark.

Introduction: Cardiac rehabilitation improves physical capacity, health-related quality of life, and reduces morbidity and mortality among cardiac patients. Telemonitored exercise-based cardiac rehabilitation may innovate existing programmes and increase participation rates.

Objective: The purpose of this study was to investigate if telemonitored exercise-based cardiac rehabilitation improves physical capacity, muscle endurance, muscle power, muscle strength and health-related quality of life in cardiac patients.

Methods: A follow-up study on moderate risk patients with ischaemic heart and heart valve disease referred to a 12-week telemonitored exercise-based cardiac rehabilitation intervention at Aarhus University Hospital (Denmark). Participants were encouraged to exercise 60 min three times weekly with moderate/high intensity for 20 min per session. Intensity and duration of training sessions were visualised on a smartphone and uploaded to a website. Participants received individual feedback from physiotherapists on their training efforts by telephone/email. Outcome measures were changes in physical capacity (peak oxygen uptake), muscle endurance, power, and strength, and health-related quality of life between baseline end of telemonitored exercise-based cardiac rehabilitation intervention, and at six and 12 months after end of telemonitored exercise-based cardiac rehabilitation.

Results: Thirty-four participants completed telemonitored exercise-based cardiac rehabilitation. We identified a significant increase in peak oxygen uptake of 10%, in muscle endurance of 17%, in muscle power of 7%, and in muscle strength of 10% after the telemonitored exercise-based cardiac rehabilitation programme. Health-related quality of life was significantly improved by 19% in the physical and 17% in the mental component scores. We found no significant improvement in peak oxygen uptake between baseline and 12 months follow-up, but a significant improvement in muscle endurance (0.3 watts/kg, 95% confidence interval; 0.2-0.4), muscle power (0.4 watts/kg; 0.2-0.5), muscle strength (0.5 N/m/kg; 0.1-0.9), physical health-related quality of life (five points; 2-8) and mental health-related quality of life (six points; 3-9).

Discussion: This study demonstrated that the self-elected type of physical exercise in cardiac rehabilitation with telemonitoring improved all outcome measures both on the short and long-term, except for peak oxygen uptake at 12 months follow-up.
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http://dx.doi.org/10.1177/1357633X18792808DOI Listing
June 2020

Surgical closure of a ventricular septal defect in early childhood leads to altered pulmonary function in adulthood: A long-term follow-up.

Int J Cardiol 2019 Jan 2;274:100-105. Epub 2018 Jul 2.

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Dept. of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Background: The long-term outlook after surgical closure of ventricular septal defect (VSD) has traditionally been considered benign. However, there is an increasing awareness of not only late cardiac dysfunction, but also pulmonary abnormalities. The primary aim of this study was to describe pulmonary function in adults with a surgically repaired VSD, and secondarily to determine the effects of salbutamol on the potential abnormalities.

Methods: All patients (operated for a VSD in early childhood) and controls (age- and gender-matched) underwent static and dynamic spirometry, impulse oscillometry, multiple breath washout, diffusion capacity for carbon monoxide, and cardiopulmonary exercise testing. In a double-blinded, cross-over study, participants were randomized to inhalation of either 900 μg of salbutamol or placebo. The primary outcome was forced expiratory volume in 1 s.

Results: In total, 30 participants with a surgically closed VSD and 30 healthy controls were included. The VSD participants had a lower forced expiratory volume in 1 s (99 ± 13% vs. 111 ± 13%), p < 0.001, impaired forced vital capacity, (106 ± 12% vs. 118 ± 13%), p < 0.001, and lower peak expiratory flow, (95 ± 18% vs. 118 ± 19%), p < 0.001, than the control group. Also, the VSD group had a lower alveolar volume than the control group, (92 ± 10% vs. 101 ± 11%), p < 0.001, but there were no differences in the remaining pulmonary function parameters. Salbutamol reduced airway resistances in both groups, but exercise performance was not improved by salbutamol, however.

Conclusions: Adults who have undergone surgical closure of a VSD in early childhood have reduced pulmonary function compared with controls, which is unaffected by inhalation of salbutamol.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.109DOI Listing
January 2019

Mid-term function and remodeling potential of tissue engineered tricuspid valve: Histology and biomechanics.

J Biomech 2018 04 2;71:52-58. Epub 2018 Feb 2.

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Dept. of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Objective: Tricuspid valve reconstruction using a small intestinal submucosal porcine extracellular matrix (ECM) tube graft is hypothesized to be durable for six months and show signs of recellularization and growth potential. The purpose was to histologically and biomechanically test ECM valves before and after six months of implantation in pigs for comparison with native valves.

Methods: Ten 60 kg pigs were included, which survived tricuspid valve tube graft insertion. Anterior and septal tricuspid leaflets were explanted from all animals surviving more than one month and examined histologically (n = 9). Endothelialization, collagen content, mineralization, neovascularization, burst strength and tensile strength were determined for native valves (n = 5), ECM before implantation (n = 5), and ECM after six months (n = 5).

Results: Collagen density was significantly larger in ECM at implantation (baseline) compared to native leaflet tissue (0.3 ± 0.02 mg/mm vs. 0.1 ± 0.03 mg/mm, p < .0001), but collagen density decreased and reached native leaflet collagen content, six months after ECM implantation (native vs. ECM valve at six months: 0.1 ± 0.03 mg/mm vs. 0.2 ± 0.05 mg/mm, p = .8). Histologically, ECM valves showed endothelialization, host cell infiltration and structural collagen organization together with elastin generation after six months, indicating tissue remodeling and -engineering together with gradual development of a close-to-native leaflet structure without foreign body response.

Conclusions: ECM tricuspid tube grafts were stronger than native leaflet tissue. Histologically, the acellular ECM tube grafts showed evidence of constructive tissue remodeling with endothelialization and connective tissue organization. These findings support the concept of tissue engineering and recellularization, which are prerequisites for growth.
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http://dx.doi.org/10.1016/j.jbiomech.2018.01.019DOI Listing
April 2018

Vascular ring: Early and long-term mortality and morbidity after surgical repair.

J Pediatr Surg 2018 Oct 3;53(10):1976-1979. Epub 2018 Jan 3.

Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark. Electronic address:

Background: Vascular ring is a rare cause of recurrent respiratory infections, dysphagia and stridor. Surgical repair is considered safe but the long-term outcomes are unclear. The purpose of this study was to investigate the mortality and morbidity following vascular ring surgery in a single institution.

Materials And Methods: This retrospective study covers operations done at Aarhus University Hospital, Denmark between October 1983 and May 2015. Medical records were reviewed focusing on early complications and long-term complaints up to September 2017.

Results: A total of 23 patients with median age of 1.4 years (range 0.008-64 years) were operated for vascular ring. Median follow-up was 6.8 years (range 2.4-34 years). Presenting symptoms were stridor (52%), dysphagia or vomiting (52%) and recurrent respiratory infections (48%). There were no early or late deaths. Three months postoperatively, 59% reported no respiratory complaints and 50% reported normal eating habits. Long term, only 14% had no complaints. In particular, asthma (36%), persistent stridor (18%) and recurrent respiratory infections (32%) were frequent. A high number of patients developed mental illness (27%).

Conclusion: Surgery for vascular ring can be performed with low early and long-term mortality. Despite good three months outcome, the majority of patients had long-term respiratory issues. Oesophageal morbidity was low.

Level-of-evidence: 2B.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.12.022DOI Listing
October 2018

Long-term mortality in patients with atrial septal defect: a nationwide cohort-study.

Eur Heart J 2018 03;39(12):993-998

Department of Cardiothoracic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Aims: In this nationwide cohort of atrial septal defect (ASD) patients, the largest to date, we report the longest follow-up time with and without closure in childhood and adulthood compared with a general population cohort.

Methods And Results: Using population-based registries, we included Danish individuals born before 1994 who received an ASD diagnosis between 1959 and 2013. All diagnoses were subsequently validated (n = 2277). Using the Kaplan-Meier estimates and Cox proportional hazards regression adjusted for sex, birth year, and a modified Charlson Comorbidity Index, we compared the mortality of ASD patients with that of a birth year and sex matched general population cohort. The median follow-up from ASD diagnosis was 18.1 years (range 1-53 years). Patients with ASD had a higher mortality [adjusted hazard ratio (HR): 1.7; 95% confidence interval (CI): 1.5-1.9] compared with the general population cohort. The adjusted HR 30 days after closure was 1.4 (95% CI: 1.2-1.7), and it was 2.4 (95% CI: 2.0-2.9) for patients without closure.

Conclusion: Overall, ASD patients had a higher long-term mortality than a general population cohort matched on birth year and gender. Our data indicate a lower relative mortality of those ASD patients undergoing closure than the ASD patients not undergoing closure.
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http://dx.doi.org/10.1093/eurheartj/ehx687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037065PMC
March 2018