Myocardial perfusion imaging (MPI) is an effective technique used to study the left ventricular ejection function (LVEF), myocardial perfusion, wall motion, and wall thickening. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are two modalities that can be used to quantify the left global and regional perfusion at rest and stress. While PET and SPECT rely on similar principles to produce images, important differences in instrumentation and experimental applications are dictated by inherent differences in their respective physics of radioactive decay. With a sensitivity > 90% in combination with a high specificity, PET is today the best available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. Rubidium-82 (82Rb) is a PET perfusion imaging agent that has a shot half-life of 76 seconds which enables multiple sequential data acquisitions in a short duration of time. It also reduces the number of false-positive SPECT scans and artifacts from soft tissue attenuation due to the routine application of attenuation correction. However 82Rb PET imaging is under-utilized clinically due to difficulty optimizing the imaging parameters. The major challenge of 82Rb imaging is determining when to begin the image acquisition post infusion, as imaging too early results in images with high background (low contrast), and imaging too late results in noisy images due to low count statistics. 82Rb rest/stress dynamic and gated data from 16 patients were available for analysis. The FWHM of the 82Rb infusion, LV cavity and LV myocardial uptake in time activity curves were generated and compared to isolate the dominant parameter in determining image quality. The measured and actual infusion-time correlated only at rest (r = 0.93, P = 0.006). Splitting-time at rest and stress correlated (r = 0.74, P = 0.09). But the study was not able to identify a single dominant parameter that would determine the image quality due to the unpredictable nature of hemodynamics during the vasodilatory induced cardiovascular stress. First pass radionuclide angiography (FPRNA) is the gold standard for quantification of ejection fraction. We examined the quantification of the ejection function (LVEF) to determine whether the gated 82Rb PET data, using quantitative gated SPECT (QGS), would accurately predict changes in the chamber volume and correlated the results with those obtained from FPRNA technique. There was a good correlation between the resting FPRNA data and resting gated 82Rb QGS data (r= 0.81, P=0.0005) showing that this method can be applied to 82Rb PET.99mTc SPECT was considered the gold standard for this study, as it is the most widely used technique for myocardial perfusion imaging. The under-perfused area of the myocardium is defined as defect. 99mTc agents, 18F-FDG, and 82Rb can all be used for cardiac imaging 1-7. However, count rates, energy and camera differences can yield image differences that are independent of the actual biological distribution. We examined whether PET with an 82Rb-labeled tracer would provide information on defect size similar to that provided by 99mTc SPECT, using a cardiac phantom in which the true defect size is known. Since 82Rb has such a short half-life (76 seconds), filling and imaging a phantom was going be a great challenge. Hence 124I which is a high-energy radioisotope like 82Rb, was used in this phantom study as a surrogate for 82Rb. Static cardiac phantom studies with 99mTc, 18F and 124I (surrogate for 82Rb) were conducted. The percent defect sizes were measured and compared with the true defect size. Our results demonstrated that at 45% threshold, the measured defect size was representative of true defect size for 99mTc SPECT data. Using this threshold as the standard, we smoothed the 18F and 124I PET data until the measured defect size for PET was representative of the true defect size. An optimal filter cutoff frequency (Butterworth filter, cutoff = 0.80 cycles/pixel, order=5 at 45% threshold for 124I or 82Rb) was found for the PET data within the range of values studied, and this frequency was higher than the clinical norm for SPECT data. Our results also illustrated that the measured SPECT defect size varied greatly depending on the thresholds used to define a defect, whereas measure PET defect size was relatively constant over the range of cutoffs tested7. The optimal cutoff may depend on defect size, patient variability, and noise level. When assessing myocardial defect size, physical properties need to be taken into consideration, particularly when comparing images obtained using different nuclides (i.e. 82Rb or 99mTc agent perfusion and 18F FDG viability).

BACKGROUND: The ventricular septal defect (VSD), a hole between the ventricles of the heart, is the most common birth defect. Despite its commonality, little is known about related in utero functional deficits. Furthermore, although about 80% of clinical VSD resolve within a year, the long-term effects after their resolution are unknown due to lack of clinical follow-up. Chemical treatment was used to induce VSD in the rat and to investigate their functional consequences both in utero and postnatally. METHODS: Pregnant Sprague-Dawley rats were administered six 300mg/kg doses of dimethadione (DMO) by oral gavage every 12 hours beginning at 19h00 on gestational day (GD) 8 (Weston et al., 2011). DMO is the N-demethylated metabolite of the anticonvulsant trimethadione, a potent inducer of VSDs clinically and in laboratory animals. Fetal heart structure and function were examined with high-resolution ultrasound on GD 14, 15, 16, 17, and 21. A separate cohort of rats was dosed using the described paradigm, but offspring were allowed to reach parturition and mature naturally. Postnatal heart structure and function were assessed using telemetry (70 days postnatally), high-resolution ultrasound, and electrocardiography (ECG) (one year postnatally). RESULTS: Relative to controls, DMO-treated fetal rats had structural defects including VSD, an increased incidence of bradycardia (23 vs. 45%) and dysrhythmia (1.2 vs. 11%), and a reduction in cardiac output, stroke volume, and mean heart rate. Adult rats exposed to DMO in utero were more physically active, had elevated blood pressure, and had a higher incidence of dysrhythmia associated with ECG disturbances compared to controls. Both in utero and postnatal functional deficits occurred independent of septum patency. CONCLUSIONS: Gestational exposure to DMO disrupted cardiac function both in utero and postnatally, even in the absence of gross structural defects, indicating chemical exposures in utero may have permanent pathophysiological consequences on the heart. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2012-05-30 17:19:35.529

La surcharge ventriculaire droite (VD), volumétrique ou barométrique, est devenue depuis quelques années un problème de santé publique chez les patients atteints de cardiopathie congénitale.Grâce aux progrès de la prise en charge de ces patients, cette population est grandissante avec des complications spécifiques. La défaillance ventriculaire gauche (VG) est une des complications les plus graves des pathologies de surcharge du VD.L’objectif de ce travail est de déterminer s’il existe des signes d’atteinte précoce du VG chez ces patients grâce à l’étude de 2 modèles chirurgicaux de surcharge du VD (volumétrique : tétralogie de Fallot TOF et barométrique : HYPPE), et si la cardiométrie peut être un outil de dépistage.La première partie de ce travail a consisté en la validation de la technique de cardiométrie électrique chez l’homme pour mesurer le débit cardiaque mais aussi évaluer la volémie.La deuxième partie a consisté en l’analyse du VG des maladies de surcharge du VD : les résultats mettent en évidence, principalement dans le modèle HYPPE plutôt que dans le modèle TOF, une fibrose, des anomalies des tubules T, des anomalies du couplage excitation-contraction associées à une altération de la contraction et de la relaxation sarcomèrique. Même si ces premiers résultats chez le gros animal sont prometteurs, ils nécessitent d’être confirmés par l’inclusion de plus de sujets.En conclusion, la cardiométrie a montré son excellente corrélation au cathéter de conductance pour évaluer la contractilité du VG en situation de stress de façon non invasive, confirmant l’utilité de cet appareil dans le diagnostic et suivi hémodynamique de nos patients. / Right heart overload is become since few years a real public health problem in congenital heart disease. Grow up with congenital heart disease patients have become a large population and suffer from many specific complications, like left ventricular failure. Right heart overload come mainly from two ways, volume or pressure that we reproduce thanks to two porcine models: tetralogy of Fallot (TOF) for volume and pulmonary hypertension (HYPPE). We try to determine on these models if there is early left heart failure and if electrical cardiometry can detect it.First part of this work is a validation of electrical cardiometry as cardiac output evaluation and fluid management reliable tool in healthy newborns and congenital heart disease patients.Second part is a left ventricle analysis of these models: we highlighted early left ventricle lesions of fibrosis, t-tubules disorganization, excitation-contraction coupling abnormalities associated with alteration of sarcomere relaxation and contraction. Even if first results are promising on large animals, we need to include more subjects to confirm these data.In conclusion, we highlighted than electrical cardiometry had an excellent and strong correlation with conductance catheter to evaluate LV contractility by noninvasive way. These results confirm this device usefulness in diagnosis and screening of our patients.

abstract: Severe cases of congenital heart defect (CHD) require surgeries to fix the structural problem, in which artificial grafts are often used. Although outcome of surgeries has improved over the past decades, there remains to be patients who require re-operations due to graft-related complications and the growth of patients which results in a mismatch in size between the patient’s anatomy and the implanted graft. A graft in which cells of the patient could infiltrate, facilitating transformation of the graft to a native-like tissue, and allow the graft to grow with the patient heart would be ideal. Cardiac tissue engineering (CTE) technologies, including extracellular matrix (ECM)-based hydrogels has emerged as a promising approach for the repair of cardiac damage. However, most of the previous studies have mainly focused on treatments for ischemic heart disease and related heart failure in adults, therefore the potential of CTE for CHD treatment is underexplored. In this study, a hybrid hydrogel was developed by combining the ECM derived from cardiac tissue of pediatric CHD patients and gelatin methacrylate (GelMA). In addition, the influence of incorporating gold nanorods (GNRs) within the hybrid hydrogels was studied. The functionalities of the ECM-GelMA-GNR hydrogels as a CTE scaffold were assessed by culturing neonatal rat cardiomyocytes on the hydrogel. After 8 days of cell culture, highly organized sarcomeric alpha-actinin structures and connexin 43 expression were evident in ECM- and GNR-incorporated hydrogels compared to pristine GelMA hydrogel, indicating cell maturation and formation of cardiac tissue. The findings of this study indicate the promising potential of ECM-GelMA-GNR hybrid hydrogels as a CTE approach for CHD treatment. As another approach to improve CHD treatment, this study sought the possibility of performing a proteomic analysis on cardiac ECM of pediatric CHD patient tissue. As the ECM play important roles in regulating cell signaling, there is an increasing interest in studying the ECM proteome and the influences caused by diseases. Proteomics on ECM is challenging due to the insoluble nature of ECM proteins which makes protein extraction and digestion difficult. In this study, as a first step to perform proteomics, optimization on sample preparation procedure was attempted. / Dissertation/Thesis / Masters Thesis Biomedical Engineering 2018

Bakgrund: Varje år föds 1 % av alla barn i Sverige med medfött hjärtfel. Barnet med denna diagnos och dess föräldrar är i stort behov av omvårdnad. Viktiga komponenter i denna omvårdnad är stöd och uppmuntran, information på rätt nivå för mottagaren och att frågor blir besvarade. Föräldrar till barn med medfött hjärtfel lider i större mån än andra föräldrar av någon form av psykosocial stress eller ångest relaterat till barnets diagnos. Syfte: Syftet var att beskriva föräldrars upplevelser av att ha barn med medfödda hjärtfel. Metod: En litteraturstudie baserad på kvalitativa vetenskapliga artiklar. Artiklarna hittades via sökningar i CINAHL Complete, MEDLINE, Academic Search Elite och CINAHL with Full Text där tio artiklar inkluderades efter kvalitetsgranskning. Resultat: I studiens analys av artiklarna framkom fyra teman som präglade föräldrarnas upplevelser under barnens uppväxt. Dessa var; känslan av otillräcklighet och osäkerhet, en ny komplex situation, stress samt stöd och tillit. Slutsats: När ett barn får diagnosen medfött hjärtfel står hela familjen inför en ny situation som innebär stora omställningar i vardagen. Stress var en konstant börda och föräldrarna upplevde att de kände sig otillräckliga och osäkra i föräldrarollen. Behovet av stöd och tillit, från både vårdpersonal, släkt och vänner, var stort för att orka med situationen. Klinisk betydelse: Resultatet i denna litteraturstudie kan bidra med kunskap om föräldrars upplevelser av att ha ett barn med medfött hjärtfel. Studien kan medvetandegöra behoven hos denna grupp föräldrar, vilket kan vara till hjälp för utformning av riktlinjer inom denna ram för omvårdnad. / Background: Each year, 1% of all children born in Sweden are diagnosed at birth with congenital heart defects. The child with this diagnosis and its parents are in great need of care. Key components of this care are support and encouragement, information given at the right level for the receiver, and making sure that questions are answered. Parents of children with congenital heart disease suffer to a greater extent than other parents from some form of psychosocial stress or anxiety related to their child's diagnosis. Aim: The aim of this study was to describe parents' experiences of having children with congenital heart defects. Method: A literature study based on qualitative scientific articles. The articles were found through the databases CINAHL Complete, MEDLINE, Academic Search Elite and CINAHL with Full Text and ten articles were included after quality control. Findings: The study's analysis of the articles revealed four themes that characterized the parents' experiences as the children grew. These were; feeling of inadequacy and insecurity, new complex situation, stress, and also support and trust. Conclusion: In the new situation in which a child where diagnosed with congenital heart defect, the whole family underwent major changes in everyday life. Stress was a constant burden and parents experienced inadequacy and insecurity in the parental role. The need for support and trust from both health care workers, friends and, family was great when dealing with the situation. Relevance to clinical practice: The results of this study will hopefully contribute knowledge about parents' experiences of having a child with congenital heart defects. The study may sensitize the needs of this group of parents, which can be helpful for the development of guidelines within this framework of nursing care.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Congenital heart defects occur in approximately one percent of births every year, which makes it the most frequently occurring congenital defect in patients. The aim of this project was to use two mutant neural crest (NC) mouse models to study the mechanisms underlying congenital heart failure in utero. The first mouse model was a Pax3 systemic knockout, which was lethal by mouse gestational day 14, and had appreciably reduced numbers of migratory NC cells. The second mouse model was a Wnt1Cre-mediated NC genetic cell ablation model, which was surprisingly viable and survived to birth, despite an apparent lack of migratory NC cells. The resultant data indicated that both mouse models had similar heart structural defects including persistent truncus arteriosus, which was due to fewer or no migratory cardiac NC cells. However, in utero heart function was appreciably perturbed in Pax3 mutants when compared to that of the ablated mutant model. The loss of embryonic cardiac function in Pax3 mutants was directly attributed to a substantial decrease in the activity of the beta-adrenergic pathway. This was due to a lack of proper specification of trunk NC cells, leading to diminished levels of circulating catecholamine levels in the embryo. To definitively confirm this conclusion, poor cardiac function was successfully restored by pharmacological stimulation of the beta-adrenergic pathway via administration of isoproterenol and forskolin to pregnant dams, which led to embryonic survival of Pax3 mutants to birth. By comparison of these two mutant mouse models, perturbation in the beta-adrenergic pathway was identified as the underlying mechanism responsible for in utero heart failure and lethality in Pax3 mutant embryos. The results of this study are expected to be significant in developing future therapeutic targets for congenital heart failure in prenatal and newborn patients.

Korrektur der Fallotschen Tetralogie nach vorhergehender Palliativoperation - Langzeitergebnisse aus einem historischen Patientenkollektiv Hintergrund: Die Fallotschen Tetralogie ist ein komplexer zyanotischer Herzfehler, der erst mit dem Einsatz der Herz-Lungen-Maschine korrigiert werden kann. Zuvor erfolgte eine palliativ Operation. Seit 1960 werden Patienten mit Fallotscher Tetralogie in der Klinik für Thorax, -Herz- und Gefäßchirurgie der Universität Göttingen operiert. Ziel der Arbeit ist es, die Langzeitergebnisse eines historischen Patientenkollektivs, die zwischen 1960 und 1984 zuerst mit einer palliativen Operation behandelt und im Anschluss die Korrektur-Operation erhalten haben, zu analysieren. Methoden: Von 1960 bis 1984 erhielten 324 Patienten mit Fallotscher Tetralogie eine Korrektur-Operation nachdem zuvor eine Palliativ-Operation durchgeführt wurde. Die Datenanalyse erfolgte retrospektiv. Drei Gruppen wurden anhand der primären Palliativ-Operation gebildet: BTA-Gruppe (Blalock-Taussig-Anastomose, n=250), WCA-Gruppe (Waterstone-Cooley-Anastomose, n=57) und AD-Gruppe (verschiedene andere palliative Verfahren, n=17). Ergebnisse: Das mittlere Patientenalter war zur Korrektur-Operation in der BTA-Gruppe signifikant höher (8,45 ± 4,62 Jahre vs. 6,89 ± 2,96 Jahre in der WCA-Gruppe; p=0,0015). Die Operationsdauer war in der BTA-Gruppe mit 283 ± 105 Minuten kürzer im Vergleich zur WCA-Gruppe 314 ± 114 Minuten (p=0,32 ???). Intraoperativ wurde unter anderem eine Erweiterungsplastik mit Patch bei 64,5% durchgeführt (BTA: 63,2%, WCA: 70,2%), von diesen waren 48,8% transannulär (BTA: 44,3%, WCA: 75%). Postoperativ war eine Rethorakotomie nach der Korrektur-Operation in der WCA-Gruppe seltener (11% vs. 25% in der BTA-Gruppe; p=0,002). Die Korrektur-Operation führte in allen Gruppen zu einer effektiven, signifikanten Reduktion des rechtsventrikulären Druckes (BTA: von 96,01 ± 21,17 mmHg auf 52,75 ± 15,79 mmHg, WCA: von 97,78 ± 34,73 mmHg auf 59,05 ± 15,04 mmHg; p <0,001). Die Dauer der mechanischen Ventilation nach der Korrektur-Operation war in der BTA-Gruppe signifikant kürzer als in der WCA-Gruppe (46 ± 57 Stunden vs. 108 ± 207 Stunden; p=0,002), ebenso dauerte der Intensivaufenthalt in der BTA-Gruppe signifikant kürzer (117 ± 100 Stunden vs. 189 ± 205 Stunden in der WCA-Gruppe; p<0,001). Die Frühletalität betrug im Gesamtkollektiv 15,1%, Unterschiede zwischen den Gruppen???. Im weiteren Verlauf starben 12 weitere Patienten, so dass die Gesamtletalität 18,8% beträgt. Beim letzten Kontakt befanden sich die meisten Patienten im NYHA-Stadium II und III (NYHA-Stadium des Gesamtkollektivs: 2,3 ± 1,0; BTA-Gruppe: 2,2 ± 1,0; WCA-Gruppe: 2,7 ± 0,8). Schlussfolgerung: Die Datenanalyse zeigt, dass von den Palliativ-Operationen vor einer Korrektur-Operation bei Fallotscher Tetralogie, die BTA die vorteilhaftere Variante darstellt. Bei der Korrektur-Operation hatten die Patienten nach vorheriger BTA-Shunt-Operation eine kürzere OP-Dauer, weniger Blutungen postoperativ, sowie kürzere Beatmungs- und Intensivaufenthaltsdauer. Nach Korrektur der Fallotschen Tetralogie zeigen alle Patienten eine effiziente Verbesserung der hämodynamischen Parameter und ein gutes klinisches Langzeitergebnis. Da das optimale Operationsverfahren von mehreren Faktoren abhängt (u.a. Alter des Patienten, klinischen Zustand und anatomische Gegebenheiten), muss eine individuelle Entscheidung erfolgen und falls eine Palliativ-Operation notwendig ist, sollte die Anlage einer BTA bevorzugt werden.

<p>To assess the impact of congenital malformations in Down syndrome (DS) on morbidity, mortality and outcome at birth, information on all children with DS born in the northern part of Sweden in 1973-80 (n=211) and 1995-98 (n=88) was collected. Most common were congenital heart defects (CHD), dominated by atrioventricular septal defects (AVSD). Up to age 10 years, morbidity and mortality were more than 10 times higher in DS children with CHD than in healthy DS children. The DS children seemed more vulnerable at birth than Swedish children in general: they had increased frequencies of Cesarean sections, premature birth, asphyxia, and low birthweight, and higher proportions of children small for gestational age, regardless of the presence of CHD. Infant mortality decreased from 14.2% to 2.3% between the two periods.</p><p>All children with AVSD with and without DS born in Sweden 1973-1997 (n=801) were followed up retrospectively to 2001. Children with isolated AVSD without complex additional CHDs were studied more closely (n=502). A reduction in age at operation and postoperative mortality (from 28 to 1%) was observed. No significant difference in 5-year postoperative mortality between genders or between DS and non-DS children was found. The 5-year postoperative mortality in DS decreased from 35% in 1973-77 to about 10% in 1993-97. </p><p>CHD had a major influence on morbidity, infectionrate and mortality in DS, but not on DS birth variables. The formerly high mortality in CHD is now reduced. In isolated AVSD measures seem equally successful in DS and non-DS children. Mortality is still 3 times higher in DS children with isolated AVSD than in healthy DS children. </p>

To assess the impact of congenital malformations in Down syndrome (DS) on morbidity, mortality and outcome at birth, information on all children with DS born in the northern part of Sweden in 1973-80 (n=211) and 1995-98 (n=88) was collected. Most common were congenital heart defects (CHD), dominated by atrioventricular septal defects (AVSD). Up to age 10 years, morbidity and mortality were more than 10 times higher in DS children with CHD than in healthy DS children. The DS children seemed more vulnerable at birth than Swedish children in general: they had increased frequencies of Cesarean sections, premature birth, asphyxia, and low birthweight, and higher proportions of children small for gestational age, regardless of the presence of CHD. Infant mortality decreased from 14.2% to 2.3% between the two periods. All children with AVSD with and without DS born in Sweden 1973-1997 (n=801) were followed up retrospectively to 2001. Children with isolated AVSD without complex additional CHDs were studied more closely (n=502). A reduction in age at operation and postoperative mortality (from 28 to 1%) was observed. No significant difference in 5-year postoperative mortality between genders or between DS and non-DS children was found. The 5-year postoperative mortality in DS decreased from 35% in 1973-77 to about 10% in 1993-97. CHD had a major influence on morbidity, infectionrate and mortality in DS, but not on DS birth variables. The formerly high mortality in CHD is now reduced. In isolated AVSD measures seem equally successful in DS and non-DS children. Mortality is still 3 times higher in DS children with isolated AVSD than in healthy DS children.