| 1. |
- Arvidsson, Sandra, 1986-
(författare)
-
Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study
- 2016
-
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.
|
|
| 2. |
- Law, Lucy, 1987-
(författare)
-
Subclinical cardiovascular disease and health related quality of life in patients with radiographic axial spondyloarthritis
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. The global prevalence of r-axSpA is between 0.1-1.4%. The disease is associated with extra-musculoskeletal manifestations (EMMs) such as anterior uveitis (AU), as well as increased risk of cardiovascular disease (CVD)-related comorbidities such as atherosclerosis that significantly contribute to mortality and the burden of disease in patients with r-axSpA. The increased CVD risk is not fully explained by traditional CVD risk factors, and little is known about the difference in CVD risk profiles between the sexes. Moreover, the association of disease related variables and subclinical signs of CVD by ultrasound remain to be comprehensively investigated in a well-characterized and sex stratified patient cohort. Additionally, studies investigating factors related to health-related quality of life (HRQoL) in patients with r-axSpA acknowledge that r-axSpA patients have a lower HRQoL than the general population. However, constancy in study methods and comparison to general population controls, especially stratified by sex, are limited. Objectives: The global aim of this thesis was to explore novel methods relating to the evaluation, detection, and monitoring of factors contributing to the burden of CVD in patients with r-axSpA, and to increase knowledge about HRQoL. More specifically, to study the impact of r-axSpA on HRQoL (Paper 1) and identify novel ultrasound markers of subclinical CVD (Papers 2-4) in patients with r-axSpA, overall, stratified by sex, and compared to controls. Materials and methods: Paper 1: The Short Form-36 (SF-36) questionnaire was used to assess HRQoL in patients with r-axSpA from Western Sweden (n=210, females 42.4%). Each patient was compared to 5 age- and sex-matched persons from the SF-36 Swedish normative population database (n=1055). Papers 2-4: Ultrasound was used to (i) assess bilateral common carotid arterial (CCA) stiffness by calculation of b-stiffness index and circumferential 2D strain (Paper 2); (ii) measure mean bilateral carotid intima media thickness (cIMT) and investigate its relationship with biomarkers of inflammation (Paper 3); and (iii) assess the mean thickness of the epicardial adipose tissue (EAT) deposit and its associations with traditional CVD related risk factors (Paper 4). Papers 2-4 used a well characterized patient group from Northern Sweden (‘Backbone cohort’, n=155, female 31.0%). The control group for paper 2 included 46 age- and sex- matched persons from the local population, with no traditional CVD risk factors. The control group for papers 3 and 4, was derived from the Umeå region Swedish CArdioPulmonary bioImaging Study (SCAPIS) recall study (n= 400, females 51.0%). All results were presented stratified by sex. Uni- and multi-variate regression analysis methods were used to evaluate associations with disease and demographic variables. All studies were of cross-sectional design.Results: Paper 1: Patients exhibited significantly lower HRQoL compared to controls (P<0.001). Upon stratification by sex, both sexes scored significantly lower physical compared to the mental HRQoL scores. Multivariable logistic regression analysis found that patients with a longer disease duration, worse physical function (assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), high disease activity (measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)), or who lived alone had significantly lower physical HRQoL. Lower mental HRQoL was associated with fatigue, high ASDAS and living alone. Some differences in sex were also found. Paper 2: Patients had higher mean bilateral CCA b-stiffness index, and lower 2D CCA circumferential strain, compared to controls. Multivariate linear regression analysis found that several disease related parameters, in addition to age, were related to 2D circumferential strain (R2 0.33), whereas only age was related to b-stiffness index (R2 0.19). Paper 3: Linear regression analysis, with various adjustment models, showed that patients had increased cIMT compared to controls. White blood cell (WBC)- and monocyte- count were the only inflammatory biomarkers associated with cIMT. This association was only seen in male patients and remained after adjustments. Paper 4: Mean EAT was thicker in r-axSpA patients overall and stratified by sex compared to controls. No difference in mean EAT was found between the sexes. There were borderline significant associations between EAT thickness and cholesterol levels in male patients.Conclusion: Patients with r-axSpA have decreased HRQoL and increased subclinical indicators of CVD compared to controls. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may be improved in patients with r-axSpA. Additionally, ultrasound methods are non-invasive, and easily obtainable, offering additional insights into the factors that influence the risk of CVD in r-axSpA patients. Although further studies are required to validate novel ultrasound methods, these techniques represent a powerful approach to non-invasively to detect, monitor, and help manage CVD related comorbidities.
|
|
| 3. |
- Calcutteea, Avin, 1978-
(författare)
-
New insights in the assessment of right ventricular function : an echocardiographic study
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined. Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function.Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software.Results:1- Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls: p<0.01 & p<0.01, Group 1: p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract.2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell (p=0.04).3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls.Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.
|
|
| 4. |
- Gustafsson, Ulf, 1976-
(författare)
-
Ventricular rotation and the rotation axis : a new concept in cardiac function
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.
|
|
| 5. |
- Henein, Mark, 1960-
(författare)
-
Left atrial function in health and disease
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Objectives of this thesis are:1) To study possible atrial interaction in patients with right and left ventricular outflow tract obstruction due to significant pulmonary (PS) and aortic valve stenosis (AS), respectively.2) To assess left atrial (LA) intrinsic myocardial function and its relationship to indirect measures of left ventricular (LV) filling pressures in patients with paroxysmal atrial fibrillation (PAF).3) To test the hypothesis that the LA function is affected in patients with pulmonary arterial hypertension (PAH).4) To test the hypothesis that raised LA pressure as shown by pulmonary capillary wedge pressure (PCWP) correlates with severity of LA intrinsic systolic function.We conducted 4 studies to achieve the objective sabove.Study IMethods:We studied 41 PS patients (age 36±10 year) and 41 AS patients (age 35 ± 12 year) and compared them with 27 controls (age 30 ± 7 year). RV and LV filling were recorded by conventional PW Doppler. Biventricular segmental function was studied using the PW tissue Doppler imaging (TDI) and M mode techniques.Results:The 2 patient groups had similar degree of ventricular outflow tract obstruction. In the pressureoverloaded ventricle, global systolic function was preserved but long axis function was impaired.Patients had higher peak late filling (Awave)and TDI late diastolic (a’) velocities recorded in the disease free ventricles despite having similar peak early filling velocities (E wave), E wave deceleration time and E/e’ ratios were not different from controls (p>0.05 for all). The accentuation of atrial activity (A wave) was moderately correlated with the degree of contra lateral ventricular outflow tract obstruction (p<0.001 for both).Conclusion:In the pressure overloaded ventricle long axis function is more sensitive than global function in revealing myocardial dysfunction. The increased contra lateral atrial systolic activity suggests an evidence for atrial interaction in the form of ‘Cross Talk’.Study IIMethods:Twentyfive PAF patients (age 68±7 year, 10 males) with Doppler signs of raised filling pressures were studied using speckle tracking echocardiography and compared with 21 controls. LA segmental longitudinal strain (S), strain rate (SR) and myocardial velocities during atrial systole were measured as were LA longitudinal and transverse diameters. Markers of LV filling pressures were E/A andE/e’.Results:LA longitudinal diameter was larger in patients (5.5±0.6 vs. 4.8±0.6cm,p<0.01) and global LAS and SR were reduced (p<0.05 for both) and correlated with E/A (r=0.52 and r=0.43, p<0.05 for both). LA segmental S and SR were uniformly reduced compared with controls (p<0.05 for all) and also correlated with E/A (p<0.05 for all). LA myocardial velocities (TDI) were highest at the annular level and lowest at the rear in both patients and controls (p<0.01 for all), with the absolute values at each level not different between groups. Myocardial velocities negatively correlated with E/A at the annular level only in patients (septal: r=0.52; lateral: r=0.62, p<0.01 for both).Conclusion:In PAF patients, LA systolic function is suppressed and is directly related to the raised filling pressures. While intrinsic global and segmental function can reproducibly be studied by S and SR, myocardial velocities reflect only regional motion. These findings provide a sound explanation to the known beneficial effect of vasodilators in PAF patients.Study IIIMethods:We studied LA size and reservoir function in 35 patients (age 63 ± 15 years, 16 male) with idiopathic PAH using speckle tracking echocardiography who also underwent right heart catheterization simultaneously to assess pulmonary artery systolic pressure, and compared them with 27 age and gender normal controls.Results:In PAH patients, LA longitudinal diameter was not different from controls but transverse diameter was reduced (3.0 ± 0.6 vs. 3.7 ± 0.5cm, p<0.001). LA lateral wall strain rate (SR) during LV systole (atrial reservoir function was reduced at annular (p<0.001) and mid cavity (p<0.01) levels as were septal segments (p<0.03, for both) compared to controls. Opposite to controls, the two LA walls responded differently to right heart pressures. Lateral SR inversely correlated with pulmonary artery systolic pressure (PASP) (annular: r=0.45, p<0.005 and midcavity: r=0.43, p<0.01), but not with right atrial pressure (RAP). In contrast, septal SR inversely correlated with RAP (annular: r=0.39, p=0.02 and midcavity: r=0.38, p=0.03) but not with PASP.Conclusion:In patients with PAH, LA reservoir function is significantly impaired showing reduced myocardial strain rate properties. In addition,segmental function differs in their response to raised right heart pressures with the septal wall related to right atrial pressure and lateral wall related to the PASP. These findings suggest an evidence for atrial interaction in PAH, which is likely to have significant impact on LV performance.Study IVMethods:We studied 46 patients, mean age 61 ± 13 years, 17 males, of various etiologies with exertional breathlessness who underwent right heart catheterization and simultaneous transthoracic Doppler echocardiography using spectral, tissue Doppler and speckle tracking echocardiography techniques for assessing LA structure and function.Results:PCWP correlated with direct measurements of LA structure and function: LA volume (r= 0.43, p<0.01), LA global systolic strain rate (r=0.79, p<0.001) and to a lesser extent with LA systolic filling fraction (r=0.52, p<0.001). PCWP also correlated with indirect measures of LA pressure: LV E/A (r=0.66, p<0.001), E wave deceleration time (r=0.54, p<0.001), lateral E/e’ (r=0.49, p<0.001) and LV isovolumic relaxation time (r=0.36, p<0.01). LA strain rate was 78% sensitive and 84% specific in identifying patients with PCWP>15 mmHg, having accurately predicted PCWP in 63% of the cases.Conclusion:PCWP correlates with LA intrinsic systolic function and to a much lesser degree with indirect Doppler measures of raised LV filling pressures. These findings should have significant clinical implications in identifying breathless patients with raised LA pressure.
|
|
| 6. |
- Tossavainen, Erik, 1977-
(författare)
-
In the hands of ohm : hemodynamic aspects in pulmonary hypertension
- 2019
-
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.
|
|
| 7. |
- Åström Malm, Ida
(författare)
-
Clinical aspects of arterial wall stiffness with a focus on abdominal aortic aneurysm
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiovascular diseases are the most common type of age-related diseases and can affect health in several ways. As a result of increased life expectancy around the world, the prevalence of cardiovascular diseases is expected to increase. Early detection of cardiovascular morbidity is important to reduce mortality and also to improve cardiovascular health. Arterial stiffness is a well-known independent predictor of cardiovascular morbidity and mortality. The central arterial walls become stiffer with age, which has an important impact on cardiac work. The development of arterial stiffness is not an immutable and inexorable process. Instead, it should be seen as a potential target of interventions that aim to slow the vascular ageing process. Arterial stiffness in individuals affected by abdominal aortic aneurysm (AAA) is an understudied area. AAA is a disease that predominantly affects elderly males. The disease is usually asymptomatic, but a rupture of the aneurysm is life threatening. Even without rupture, individuals with an AAA have an increased risk of other major cardiovascular events, but the underlying mechanisms of this increased risk are unclear.Aim: The overall aim of the research in this thesis was to investigate clinical aspects of arterial stiffness with a focus on AAA.Methods: All studies in this thesis used a quantitative and a cross-sectional design. Paper I compared elderly hypertensive females with elderly hypertensive males and examined the effects of FBN1 genotypes within each sex. The study cohort in Paper I underwent physiological cardiovascular examinations with a focus on pulse wave analysis and blood pressure. In addition, blood samples were taken after overnight fasting. The study cohorts in Papers II–IV were males with AAA and age-matched controls without AAA. The participants underwent physiological cardiovascular examinations, and blood samples were taken after overnight fasting. In Paper II, the speed and shape of the pulse wave and blood pressure were studied non-invasively to evaluate the properties of the arterial system. In Paper III, the heart was studied using two-dimensional ultrasound with a focus on evaluation of the function of the left ventricle. In Paper IV, analyses of IL-10 levels were added to the previously performed studies.Results: A sex-related difference was found in the augmentation index (females: 36%; males 33%; p<0.001) and systolic blood pressure (females: 169 mmHg; males: 162 mmHg; p<0.05) of the elderly hypertensive participants in Paper I. In addition, females, but not males, displayed differences in augmentation index and systolic blood pressure among different FBN1 genotypes; females with the FBN1 2/3 genotype had higher augmentation index (p<0.05) and systolic blood pressure (p<0.05) than those with the FBN1 2/2 and 2/4 genotypes. In Paper II, differences in central pulse wave velocity (12.3 m/s versus 10.9 m/s; p<0.001) and peripheral pulse wave velocity (9.4 m/s versus 9.1 m/s; p<0.05) were seen between patients with AAA and controls. In Paper III, patients with AAA had lower left ventricular ejection fraction (55±8% versus 57±7%) and global longitudinal strain (19±3% versus 20±3%) than controls (both p<0.05). Moreover, the patients with AAA had lower mitral annular plane systolic excursion and higher E/e' compared with the controls (both p<0.05). In Paper IV, patients with AAA had higher levels of Interleukin-10 (21.5±14.0 ng/ml versus 16.6±9.3 ng/ml) compared with controls (p<0.01), and within the AAA cohort, patients with diabetes had higher levels of Interleukin-10 than those without diabetes (26.4±17.3 versus 20.4±13.0; p<0.05).Conclusion: The results from this thesis highlight the possibility to use pulse wave velocity and augmentation index for risk stratification in patients already affected by cardiovascular diseases. The results contribute new knowledge about arterial stiffness and left ventricle function in males with AAA. Moreover, they contribute knowledge to support new and individualised treatments for arterial stiffness in males with AAA in the future.
|
|
