Myocardial Work in Patients Hospitalized With COVID‐19:Relation to Biomarkers, COVID‐19 Severity, and All‐Cause Mortality

BACKGROUND: COVID‐19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID‐19. We hypothesized that GWI was associated with disease severity and all‐cause death in patients with COVID‐19. METHODS AND RESULTS: In a multicenter study of patients admitted with COVID‐19 (n=305), 249 underwent pressure‐strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), disease severity (oxygen requirement and CRP [C‐reactive protein]), and all‐cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT‐proBNP was observed, with increasing NT‐proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100–mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow‐up (median, 58 days). In multivariable Cox regression, GWI was associated with all‐cause death (hazard ratio, 1.08 [95% CI, 1.01–1.15], per 100–mm Hg% decrease), but did not increase C‐statistics when added to clinical parameters. CONCLUSIONS: In patients admitted with COVID‐19, our findings indicate that NT‐proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all‐cause death, but did not provide prognostic information beyond readily available clinical parameters. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035

A Model-based Approach for Clinical Evaluation of Left Ventricular Deformation

Assessment of left ventricular (LV) deformation is essential for clinical evaluation of LV function and cardiac images are frequently used to evaluate the LV motion and function. By combining the images with mathematical models more information may be extracted from the images. The work presented in this thesis has focused on using the finite element (FE) method to describe the LV and its deformation and combining this method with images of the heart to extract more information about the deformation. We developed a method that estimated the LV deformation by manually tracking distinct anatomical landmarks (fiducial markers) through the cardiac cycle in 3 dimensional (3D) images of the heart. The motion of the nodal parameters of an FE mesh shaped to the geometry of the LV was fitted to the motion of the fiducial markers and thus provided a means to describe the motion. The sparsity of the fiducial markers made the fitting problem under-constrained so a parameter distribution model (PDM) of likely motions were constructed from a historical database of cases where FE meshes had been fitted to the motion of magnetic resonance (MR) tagged data. The estimated deformation from the fiducial marker fitting was filtered through the PDM and the resulting deformation corresponded well when compared to the deformation obtained from MR tagging in 13 normal subjects. A method that decomposed the LV deformation into different deformation modes such as longitudinal shortening, wall thickening, and twisting was developed. The nodes of a subject’s LV FE mesh were displaced according to each deformation mode and the relative contribution of each mode to the total deformation measured by MR tagging was quantified by calculating a coefficient for each mode. A study that compared 13 young normal subjects with 13 older diabetes patients showed that the patients had a significantly lower degree of longitudinal shortening and wall thickening but a higher degree of longitudinal twist. The LV deformation is influenced by cardiac disease via the material properties of the myocardium. We investigated the effects of the material parameter values on the LV deformation in a simulation study using an FE model of the LV. A description of the myocardial microstructure and a passive and active constitutive law was included in the model. The cardiac cycle was simulated from the beginning of diastasis through to the end of ejection by applying appropriate boundary conditions. The different deformation modes between end diastole and end systole were extracted and quantified for different sets of material parameters. We found that stiffer material properties particularly in the myocardial sheet direction impaired longitudinal shortening and wall thickening. A sensitivity analysis was carried out to look at the various material parameters’ influence on LV wall strains during passive inflation. The analysis showed a high degree of coupling of the parameters in the constitutive law, which indicated an overparameterization of the law. A parameter estimation study revealed the same problem. Most of the parameters were set to constant values and only one parameter in each of the three microstructural directions were estimated during the passive inflation phase using synthetic strain data as measurements. This still gave good estimates of the stress-strain relationships in the fiber and sheet directions.Papers I and II reprinted with kind permission of Elsevier, ScienceDirec

Factors determining the magnitude of the pre-ejection leftward septal motion in left bundle branch block

AIMS: An abnormal large leftward septal motion prior to ejection is frequently observed in left bundle branch block (LBBB) patients. This motion has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate factors that influence its magnitude. METHODS AND RESULTS: Left (LVP) and right ventricular (RVP) pressures and left ventricular (LV) volume were measured in eight canines. After induction of LBBB, LVP and, hence, the transmural septal pressure (P(LV–RV) = LVP–RVP) increased more slowly (P < 0.01) during the phase when septum moved leftwards. A biventricular finite-element LBBB simulation model confirmed that the magnitude of septal leftward motion depended on reduced rise of P(LV–RV). The model showed that leftward septal motion was decreased with shorter activation delay, reduced global or right ventricular (RV) contractility, septal infarction, or when the septum was already displaced into the LV at end diastole by RV volume overload. Both experiments and simulations showed that pre-ejection septal hypercontraction occurs, in part, because the septum performs more of the work pushing blood towards the mitral valve leaflets to close them as the normal lateral wall contribution to this push is lost. CONCLUSIONS: Left bundle branch block lowers afterload against pre-ejection septal contraction, expressed as slowed rise of P(LV–RV), which is a main cause and determinant of the magnitude of leftward septal motion. The motion may be small or absent due to septal infarct, impaired global or RV contractility or RV volume overload, which should be kept in mind if this motion is to be used in evaluation of CRT response

Dysfunction of the systemic right ventricle after atrial switch: physiological implications of altered septal geometry and load

Atrial switch operation in patients with transposition of the great arteries (TGA) leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for noninvasive work calculation based on echocardiography. In 14 TGA patients (32 ± 6 yr, means ± SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients, septal longitudinal strain was reduced to −14 ± 2 vs. −20 ± 2% in controls ( P &lt; 0.01) and septal work was reduced from 2,046 ± 318 to 1,146 ± 260 mmHg·% ( P &lt; 0.01). Septal circumferential strain measured in a subgroup of patients was reduced to −11 ± 3 vs. −27 ± 3% in controls ( P &lt; 0.01), and a reduction of septal work (540 ± 273 vs. 2,663 ± 459 mmHg·%) was seen ( P &lt; 0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV. NEW &amp; NOTEWORTHY We have demonstrated that transposition of the great arteries patients with systemic right ventricles (RVs) have reduced function of the interventricular septum (IVS). Since the IVS is constructed to eject into the systemic circulation, it may seem unexpected that it does not maintain function when being part of the systemic RV. By applying the principles of regional work, wall tension, and geometry, we have identified unfavorable working conditions for the IVS when the RV adapts to systemic pressures

Estimating Myocardial Contraction Using Miniature Transducers on the Epicardium

This paper describes an ultrasound system to monitor cardiac motion using miniature transducers attached directly to the epicardial surface. Our aim was to develop both a research tool for detailed studies of cardiac mechanics and a continuous, real time system for peri-operative evaluation of heart function. The system was tested on a porcine model. Two 3 mm diameter, 10 MHz ultrasound transducers were sutured to the epicardial surface. As the epicardial surface was the reference for the velocity and strain estimations, this procedure compensated for the motion of the heart. The short distance allowed for the use of high frequencies and pulse repetition rates. The system was driven in pulse-echo mode, using electronics developed for the application, and radio frequency (RF) lines were recorded at a pulse repetition rate of 2500 s-1. The endocardial border was detected using an algorithm based on fuzzy logic with filtration to reduce noise and remove outliers, and the myocardium was divided into four layers. Inside the myocardium, radial tissue velocity as a function of depth was calculated from the recorded RF signals, and the velocity estimates were used to estimate radial strain rate and strain and to track the motion of the myocardial layers. The scope of this paper is technical, giving a detailed description of system design, hardware electronics and algorithms, with examples of processed velocity patterns and myocardial strain curves. The results from this study on a porcine model demonstrate the system's ability to estimate myocardial velocity and strain patterns and to track the motion of the myocardial layers, thereby obtaining detailed information of the regional function of the myocardium.status: accepte

Dynamic gravity compensation does not increase detection of myocardial ischemia in combined accelerometer and gyro sensor measurements

Previous studies have shown that miniaturised accelerometers can be used to monitor cardiac function and automatically detect ischemic events. However, accelerometers cannot differentiate between acceleration due to motion and acceleration due to gravity. Gravity filtering is essential for accurate integration of acceleration to yield velocity and displacement. Heart motion is cyclic and mean acceleration over time is zero. Thus, static gravity filtering is performed by subtracting mean acceleration. However, the heart rotates during the cycle, the gravity component is therefore not constant, resulting in overestimation of motion by static filtering. Accurate motion can be calculated using dynamic gravity filtering by a combined gyro and accelerometer. In an animal model, we investigated whether increased accuracy using dynamic filtering, compared to using static filtering, would enhance the ability to detect ischemia. Additionally, we investigated how well the gyro alone could detect ischemia based on the heart’s rotation. Dynamic filtering tended towards lower sensitivity and specificity, using receiver operating characteristics analysis, for ischemia-detection compared to static filtering (area under the curve (AUC): 0.83 vs 0.93, p = 0.125). The time-varying gravity component indirectly reflects the heart’s rotation. Hence, static filtering has the advantage of indirectly including rotation, which alone demonstrated excellent sensitivity to ischemia (AUC = 0.98)

Estimating Regional Myocardial Contraction Using Miniature Transducers on the Epicardium

This paper describes an ultrasound system to monitor cardiac motion using miniature transducers attached directly to the epicardial surface. Our aim was to develop both a research tool for detailed studies of cardiac mechanics and a continuous, real time system for peri-operative evaluation of heart function. The system was tested on a porcine model. Two 3 mm diameter, 10 MHz ultrasound transducers were sutured to the epicardial surface. As the epicardial surface was the reference for the velocity and strain estimations, this procedure compensated for the motion of the heart. The short distance allowed for the use of high frequencies and pulse repetition rates. The system was driven in pulse-echo mode, using electronics developed for the application, and radio frequency (RF) lines were recorded at a pulse repetition rate of 2500 s−1. The endocardial border was detected using an algorithm based on fuzzy logic with filtration to reduce noise and remove outliers, and the myocardium was divided into four layers. Inside the myocardium, radial tissue velocity as a function of depth was calculated from the recorded RF signals, and the velocity estimates were used to estimate radial strain rate and strain and to track the motion of the myocardial layers. The scope of this paper is technical, giving a detailed description of system design, hardware electronics and algorithms, with examples of processed velocity patterns and myocardial strain curves. The results from this study on a porcine model demonstrate the system's ability to estimate myocardial velocity and strain patterns and to track the motion of the myocardial layers, thereby obtaining detailed information of the regional function of the myocardium