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Assessment of Ventricular Function in Normal and Failing Hearts Using 4D Flow CMR
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heart failure is a common disorder and a major cause of illness and death in the population, creating an enormous health-care burden. It is a complex condition, representing the end-point of many cardiovascular diseases. In general heart failure progresses slowly over time and once it is diagnosed it has a poor prognosis which is comparable with that of many types of cancer.

The heart has an ability to adapt in response to long lasting increases in hemodynamic demand; the heart conforms its shape and size in order to maintain adequate cardiac output. This process is called remodeling and can be triggered by pathologies such as hypertension or valvular disease. When the myocardial remodeling is maintained chronically it becomes maladaptive and is associated with an increased risk of heart failure.

In many cases, heart failure is associated with left bundle branch block (LBBB). This electrical disturbance leads to dyssynchronous left ventricular (LV) contraction and relaxation which may contribute to cardiac dysfunction and ultimately heart failure. Mechanical dyssynchrony can be treated with cardiac resynchronization therapy (CRT). However, many heart failure patients do not demonstrate clinical improvement despite CRT.

Blood flow plays an important role in the normal development of the fetal heart. However, flow-induced forces may also induce changes in the heart cells that could lead to pathological remodeling in the adult heart. Until recently, measurement tools have been inadequate in describing the complex three-dimensional and time-varying characteristics of blood flow within the beating heart.

4D (3D + time) flow cardiovascular magnetic resonance (CMR) enables acquisition of three-dimensional, three-directional, time-resolved velocity data from which visualization and quantification of the blood flow patterns over a complete cardiac cycle can be performed. In this thesis, novel 4D Flow CMR based methods are used to study the intraventricular blood flow in healthy subjects and heart failure patients with and without ventricular dyssynchrony in order to gain new knowledge of the ventricular function.

Different flow components were assessed in normal heart ventricles. It was found that inflowing blood that passes directly to outflow during the same heartbeat (the Direct Flow component) was larger and possessed more kinetic energy (KE) than other flow components. Diastolic flow through the normal heart appears to create favorable conditions for effective systolic ejection. This organized blood flow pattern within the normal LV is altered in heart failure patients and is associated with decreased preservation of KE which might be unfavorable for efficient LV ejection. Inefficient flow of blood through the heart may influence diastolic wall stress, and thus contribute to pathological myocardial remodeling.

In dyssynchronous LVs of heart failure patients with LBBB, Direct Flow showed even more reduced preservation of KE compared to similarly remodeled LVs without LBBB. Furthermore, in LBBB patients, LV filling hemodynamic forces, acting on the myocardium, were more orthogonal to the main flow direction compared to patients without LBBB. Deviation of LV flow forces and reduction of KE preservation and may reflect impairment of LV diastolic function and less efficient ensuing ejection related to dyssynchrony in these failing ventricles.

Blood flow patterns were also studied with respect to fluctuations of the velocity of the flow (turbulent flow) in normal and failing LVs. In failing hearts, turbulent kinetic energy (TKE) was higher during diastole than in healthy subjects. TKE is a cause of energy loss and can thus be seen as a measure of flow inefficiency.

Elucidating the transit of multidimensional blood flow through the heart chambers is fundamental in understanding the physiology of the heart and to detect abnormalities in cardiac function. The 4D Flow CMR parameters presented in this thesis can be utilized to detect altered intracardiac blood flow and may be used as markers of deteriorating cardiac function, pathological remodeling and mechanical dyssynchrony in heart failure.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2017. , p. 68
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1592
National Category
Cardiac and Cardiovascular Systems Medical Laboratory and Measurements Technologies Biomedical Laboratory Science/Technology Anesthesiology and Intensive Care Physiology
Identifiers
URN: urn:nbn:se:liu:diva-141006DOI: 10.3384/diss.diva-141006ISBN: 9789176854389 (print)OAI: oai:DiVA.org:liu-141006DiVA, id: diva2:1142711
Public defence
2017-10-20, Hugo Theorell, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2017-10-04 Created: 2017-09-20 Last updated: 2018-01-13Bibliographically approved
List of papers
1. 4-D blood flow in the human right ventricle
Open this publication in new window or tab >>4-D blood flow in the human right ventricle
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2011 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 301, no 6, p. H2344-H2350Article in journal (Refereed) Published
Abstract [en]

Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 +/- 0.3 mJ) than the other flow components (P andlt; 0.001 and P andlt; 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P andlt; 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

Place, publisher, year, edition, pages
American Physiological Society, 2011
Keyword
cardiac disease, interventricular function, kinetic energy, phase-contrast magnetic resonance imaging, pump physiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74161 (URN)10.1152/ajpheart.00622.2011 (DOI)000298325200020 ()
Note
Funding Agencies|Swedish Research Council||Swedish Heart-Lung Foundation||Emil and Wera Cornell Foundation||Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
2. Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
Open this publication in new window or tab >>Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
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2015 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 4, p. 1021-1029Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients with dilated cardiomyopathy (DCM).

Methods: 4D flow and morphological MRI-data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic time frame. At peak early (E) and late (A) diastolic filling, the TKELV was compared to transmitral peak velocity, LV diameter and mitral annular diameter.

Results: In the majority of all subjects, peaks in TKELV could be observed at E and A. Peak TKELV at E was not different between the groups, and correlated with mitral annular dimensions. Peak TKELV at A was higher in DCM patients compared to healthy subjects, and was related to LV diameter and transmitral velocity.

Conclusions: In normal LVs, TKE values are low. Values are highest during early diastole, and diminish with increasing LV size. In a heterogeneous group of DCM patients, late diastolic TKE values are higher than in healthy subjects. Kinetic energy loss due to elevated late diastolic TKE may reflect inefficient flow in dilated LVs.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keyword
Magnetic resonance imaging, blood flow, turbulent flow, cardiac function, diastolic dysfunction, heart failure
National Category
Medical Engineering Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-99957 (URN)10.1002/jmri.24633 (DOI)000351521700019 ()
Note

Contract grant sponsor: Swedish Heart-Lung Foundation; Contract grant sponsor: Swedish Research Council; Contract grant sponsor: European Research Council.

Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2017-12-06Bibliographically approved
3. Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block
Open this publication in new window or tab >>Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2971Article in journal (Refereed) Published
Abstract [en]

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-138889 (URN)10.1038/s41598-017-03089-x (DOI)000402879800027 ()28592851 (PubMedID)
Note

Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]

Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2018-04-17

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