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- Tossavainen, Erik, 1977-
(författare)
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In the hands of ohm : hemodynamic aspects in pulmonary hypertension
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congestive heart failure (CHF) is one of the most challenging diseases in terms of health care demand and mortality, in the western world. Despite major breakthroughs in the fields of diagnosis and treatment over the three last decades, the management of CHF still remains challenging.CHF is defined as inability of the heart to supply sufficient blood flow to meet the needs of the body. This definition however, may be an oversimplification of a complex pathophysiological process since patients with overt CHF may have normal, or even supernormal cardiac output at the expense of increased filling pressures, which subsequently leads to the development of post capillary pulmonary hypertension (PH). In the presence of advanced CHF, clinical signs and symptoms are obvious at rest. However, the majority of affected individuals do not experience any discomfort at rest and may demonstrate normal findings when assessed. Small increases in systemic blood pressure and or venous return, caused by activity may result in severe elevation of filling pressures if left ventricular compliance is significantly decreased. This example highlights the need to perform cardiac investigations during stress to provoke symptoms. Increased pulmonary vascular resistance (PVR), commonly found in pre-capillary PH, is a condition that shares many symptoms with CHF, and is also associated with poor prognosis. Even though the disease is located within the lung vessels, it is highly important and challenging task differentiating pre- and post-capillary PH. Since treatment differs considerably and may be detrimental in case of misdiagnosis, additional sensitive and reliable screening methods are crucial to aid in differentiation.Methods: Out of the four studies included in this thesis, three were conducted solely at Norrland’s University Hospital, while patients in the third study were recruited and examined at Uppsala Akademiska Hospital. All included patients had idiopathic dyspnea and were admitted for right heart catheterization (RHC), which is gold standard with regards to hemodynamics. Echocardiographic examinations were performed simultaneously with RHC, except in the Uppsala study, wherein echocardiography were performed within 3 days to the RHC.Echo-Doppler derived pulmonary artery acceleration time (PAcT) is an easily assessed parameter, indicating elevated pulmonary artery systolic pressure (PASP) and pulmonary artery resistance (PVR). PAcT was tested as a screening method for identification and differentiation of pre and post- capillary PH in a cohort of 56 patients (study 1).The ability to calculate PVR non-invasively, using novel echocardiographic measurements, was made by replacing the invasive pressure and flow components that constitutes the foundation of the PVR = (mean pulmonary artery pressure – Pulmonary capillary wedge pressure (PCWP)) /cardiac output), with novel echocardiographic measurements. PVR = mPAP-Chemla – Left atrial strain rate during atrial systole (LASRa) / Cardiac Output-Echo (study 2).Invasively measured left ventricular filling pressure in response to passive leg lifting, and its ability to predict pathological increase in left ventricular filling pressures during supine bicycling, was tested in a population of 85 patients with normal left ventricular ejection fraction (LVEF) and suspicion of CHF based on NT-proBNP levels alone were investigated (Study 3).Finally, an evaluation of standard and novel Doppler echocardiographic parameters, potentially useful in identifying patients who may develop increased filling pressures during passive leg lifting (PLL), was carried out (study 4).Results:Study 1: PAcT correlated negatively with pulmonary artery systolic pressure (PASP) (r = -0.60, p < 0.001) and PVR (r = -0.57, p < 0.001). PAcT of <90 ms had a sensitivity of 84% and a specificity of 85% in identifying patients with PVR ≥ 3.0 WU. Regardless of normal or elevated left sided filling pressures, PAcT differed significantly in patients with normal, compared to those with elevated levels of, PVR (p < 0.01). A significant difference was also found on comparison of the PAcT/PASP ratio (p < 0.01), with a lower ratio among patients with PVR ≥ 3.0. WU.Study 2: We prospectively used Doppler and 2D echocardiography in 46 patients with sinus rhythm which revealed that left atrial strain rate during atrial systole (LASRa) had the highest significant positive correlation with PCWP (r2 = 0.65, P < 0.001). By adopting a linear line of best-fit, LASRa may therefore be substituted for PCWP. Subsequently, LASRa was substituted into the PVR equation. This novel echocardiographically derived PVR calculation, significantly correlated with RHC generated PVR values (r2 = 0.69, P < 0.001) and minor drift (+0.1WU) when assessed by Bland Altman analysis.Study 3: Only 22% (11/51) of patients with elevated NT-proBNP had PCWP above normal levels at rest. However, in response to PLL, 47% of patients developed elevated PCWP, and the majority of this 47% subsequently developed pathological pressure levels while performing supine cycling exercise. Thus, the likelihood of developing high LVFPs during exercise could be determined by PLL, with a sensitivity and specificity of 90%.Study 4: At rest, left atrial volume indexed to body mass index (BMI) (LAVI) and mitral deceleration time (DT) were independently related to PCWP during PLL. However, during PLL univariate regression analysis revealed LASRa (β = -0.77, P <0,001) and E/LVSRe (β = 0.47, P < 0,021) most related to PCWPPLL. Multiple regression analysis fortified LASRa and E/LVSRe as relevant independent parameters useful in the assessment of filling pressure during PLL.Conclusion: A PAcT < 90ms is strongly suggestive of increased PVR (>3.0 WU). Based on study 1, there is clear evidence suggesting that these findings apply irrespective of LVFPs. PAcT can potentially serve as a rapid screening tool for estimation of PVR, however, is not useful if the exact level of PVR is required. In this case, an established PVR calculation method is preferred, and could be performed with higher precision by inclusion of echocardiography derived LASRa as a surrogate measure of PCWP. Insufficient LV compliance results in the inability to cope with increased cardiac preload. Nt-proBNP is secreted when the myocardium is stretched, however only a small portion of patients within the CHF group (study 3) had a high PCWP at rest. Nearly half of the study population with elevated NT-proBNP showed increased PCWP during PLL, which is indicative of underlying ventricular stiffness. By performing this preload increasing maneuver, patients predisposed to developing high filling pressure during supine cycling could be identified with high sensitivity and specificity. Echocardiography, in comparison with RHC, is more accessible, safer and requires less resources and time, thus is an appealing option in the quest to identify additional, non-invasive methods reflective of invasive pressures, which could be useful in the assessment of filling pressure during different loading conditions. LAVI at rest, LASRa and E/LVSRe during PLL, proved independently related to PCWP during PLL.
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| 2. |
- Arvidsson, Sandra, 1986-
(författare)
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Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.
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| 3. |
- Henriksson, Kristina
(författare)
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Skolbesökets osynliga bedömningsprocesser : en studie av hur lärarstudenters yrkeskunnande bedöms under verksamhetsförlagd utbildning
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis treats the assessment of student teachers’ professional skills within the school-based section of Swedish teacher education, more specifically the school visits organized by the university. School visits ordinarily consist of an observed lesson, followed by a post-observation conference. School-based teacher education is regarded as a specific educational element, where the education is transferred to the organisation of professional teachers who educate the student teacher. However, there is a lack of direct research about what happens to the assessment of the student teacher’s proficiency when the assessment system of the education is applied outside the university domain. Research shows that there is tension regarding the view of professional skills between players in teacher education and school organisations, and uncertainties regarding the mandate to develop the student teacher’s professional skills. From a political perspective the school visit is perceived as a guarantee for the fulfilment of the increasing demands for equal and legally secure assessments. The aim of this thesis has therefore been to enhance the understanding of the function of assessment within school-based teacher education. The interactive assessment process of the post-observation conference has been in focus and studied through video observations and interviews. The study assumes multiple theoretical perspectives; a new institutional perspective, Goffman’s interactionist perspective and a professional theoretical perspective. The result shows that simultaneous and conflicting assessment logics guide the assessment task, creating protective and defensive interaction patterns to establish a loyal consensus between conference participants. The situation needs to be played down. The interactive patterns of the conference counteract the institutional logics of the visit, making access to information selective and limited. Judgements and feedback become invisible and the aim of the assessment process is unclear. The controlling purpose of the process, and partly also the formative purpose, is impaired. However, in the execution of assessment itself, assessment logics collaborate with interaction patterns, displaying a secondary adaptation to the situation. This collaboration contributes to a reasonable and legitimate manner of executing the assessment process, assigning meaning to the school visit.
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| 4. |
- Vanoli, Davide, 1972-
(författare)
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Vascular ultrasound for the assessment of carotid atherosclerosis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Atherosclerotic cardiovascular disease (CVD) is a common cause for mortality globally, and is expected to remain the single leading cause of death as the global population ages and as life expectancy increases.Cardiovascular screening models have been developed, and continue to be developed, to identify individuals at high-risk of CVD. This is necessary to establish prevention strategies to decrease the occurrence of an acute event or debilitating syndrome. These strategies largely take the form of lifestyle modification and pharmacological intervention. The Framingham risk score, NCEP/ATP II guidelines and SCORE risk assessment protocol are widely used screening models. Ultrasound based methods are non-invasive, affordable and have been suggested to improve assessment and definition of individual patients potential risk of CVD. Increased carotid artery intima-media thickness (cIMT) is a known and established sign of early atherosclerosis. The presence of plaque and the overall burden of atherosclerosis seems to have even greater value in predicting cerebrovascular and cardiovascular events. Ultrasound based texture characteristics of plaques such as entropy, grey scale median, discrete white area, coarseness and juxtaluminal hypoechoic black area have been proposed as useful possible predictors of plaque vulnerability. Moreover, ultrasound contrast agents have been developed to improve visualization and subsequent quantification of an atherosclerotic plaque. Considering the current available data and research, the importance of developing tools and techniques for detection and characterization of atherosclerotic changes, to indicate risk for CVD and the subsequent early intervention and prevention, appears clearly as an effort to improve public health. In this present collection of studies (4 papers) we aim to contribute to the development of clinically useful ultrasound methods and tools for the accurate assessment, understanding and management of atherosclerosis.Methods: To validate ultrasound-based methods for assessment of early signs of atherosclerosis, measured as cIMT, a total of 144 subjects underwent bilateral carotid ultrasound. In study I, the performance of an ultrasonography software capable of fully automated on-screen cIMT measurements was tested and compared with the traditional manual measurement approach. The coefficient of variation and the intraclass correlation coefficient for both methods were compared to verify the reliability and reproducibility of results generated by the new ultrasound software. To test the accessibility and possible clinical applications of this new technology tested in study I, the new software was used by novice’s scanners in study II, and the intraobserver variability of the cIMT measurements were assessed and compared with that of an expert operator. In study III, ultrasound texture characteristics of 327 plaques including entropy, grey scale median, discrete white area, coarseness and juxtaluminal hypoechoic black area were assessed as possible predictors of future cerebrovascular events in a cohort of 133 patients with symptomatic carotid stenosis waiting for carotid surgery. The reproducibility of measuring plaque area (expressed as intraclass correlation coefficient) using conventional ultrasound and contrast enhanced ultrasound was tested in study IV in an attempt to find a simple and reproducible parameter for monitoring changes in atherosclerotic burden.Results: The technology tested in study I was found to have good inter- and intra-system reproducibility compared with conventional methods. Moreover, it was found to produce reproducible results when used by expert and novice operators after a short period of training (study II), confirming the possibility for the employment of this technology in a large screening public health programs. Although such technology may have immediate practical application, other and more sophisticated ultrasound based plaque characteristics (such as grey scale median, entropy, coarseness, juxtaluminal hypoechoic black area) were not shown to be beneficial in predicting plaque vulnerability (study III). Contrast enhanced ultrasound technic tested in study IV did not improve quantification of atherosclerotic plaque burden. Conclusion: Medical ultrasound technology by using a automatically measure of carotid intima media thickness can be used with high reproducibility and also possible to be transferred to primary care by a well designed training program. Plaque characteristic using carotid ultrasound was not found to be useful in risk stratifying symptomatic patients with severe carotid stenosis. Furthermore, contrast enhanced ultrasound technique was found to have high reproducibility in plaque area assessment but not better than conventional b-mode based method in quantifying the atherosclerotic burden. Therefore, more sophisticated ultrasound based methods for assessment plaque characteristics was not found to be beneficial in predicting plaque vulnerability.
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