Hemodynamic Forces Research Articles

Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead to the focal nature of atherosclerosis. Using a step flow chamber to investigate the effects of disturbed shear (DS) and pulsatile shear (PS) on ECs in the same flow channel, we conducted single-cell RNA sequencing analyses to explore the distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters and demonstrated that DS induces EC transition from atheroprotective to proatherogenic phenotypes. Using an automated cell type annotation algorithm (SingleR), we showed that DS promoted endothelial-to-mesenchymal transition (EndMT) by inducing the transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-β) signaling, glycolysis, and fatty acid synthesis. Enolase 1 (ENO1), a key gene in glycolysis, was one of the top-ranked genes in the DS-induced EndMT cluster. Pseudotime trajectory analysis revealed that the kinetic expression of ENO1 was significantly associated with EndMT and that ENO1 silencing repressed the DS- and TGF-β-induced EC inflammation and EndMT. Consistent with these findings, ENO1 was highly expressed in ECs at the inner curvature of the mouse aortic arch (which is exposed to DS) and atherosclerotic lesions, suggesting its proatherogenic role in vivo. In summary, we present a comprehensive single-cell atlas of ECs in response to different flow patterns within the same flow channel. Among the DS-regulated genes, ENO1 plays an important role in DS-induced EC inflammation and EndMT. These results provide insights into how hemodynamic forces regulate vascular endothelium in health and disease.

Computationally Enhanced, Haemodynamic Case Study of Neointimal Hyperplasia Development in a Dialysis Access Fistula.

Oscillatory wall shear stress and related metrics have been identified as potential predictors of dialysis access outcomes; however, the absence of a simple non-invasive method for measuring these haemodynamic forces has been prohibitive to their adoption into routine clinical practice. We present a computationally enhanced, single patient case study, offering a unique insight into the haemodynamic environment surrounding the development of flow limiting neointimal hyperplasia within the efferent vein of a previously functional arteriovenous fistula (AVF). Computational fluid dynamics (CFD) simulations were used to create a quantitative map of oscillatory shear stress as well as enabling visualisation of streamline patterns within the AVF. CFD data was compared to ultrasound-based turbulence quantification and examined alongside structural and functional changes in the access site over time. This work further supports the notion that flow limiting neointimal hyperplasia development in vascular access fistulae, occurs in response to oscillatory wall shear stress, and provides proof of concept for the idea that non-invasive ultrasound turbulence quantification tools could play a role in predicting vascular access outcomes. In addition to providing insight into the haemodynamic environment surrounding the development of flow limiting neointimal hyperplasia, we hope that this paper will promote discussion and further thinking about how our learnings from in-silico studies can be incorporated into clinical practice through novel uses of existing diagnostic tools.

Control of cardiac contractions using Cre-lox and degron strategies in zebrafish

Cardiac contractions and hemodynamic forces are essential for organ development and homeostasis. Control over cardiac contractions can be achieved pharmacologically or optogenetically. However, these approaches lack specificity or require direct access to the heart. Here, we compare two genetic approaches to control cardiac contractions by modulating the levels of the essential sarcomeric protein Tnnt2a in zebrafish. We first recombine a newly generated tnnt2a floxed allele using multiple lines expressing Cre under the control of cardiomyocyte-specific promoters, and show that it does not recapitulate the tnnt2a/silent heart mutant phenotype in embryos. We show that this lack of early cardiac contraction defects is due, at least in part, to the long half-life of tnnt2a mRNA, which masks the gene deletion effects until the early larval stages. We then generate an endogenous Tnnt2a-eGFP fusion line that we use together with the zGRAD system to efficiently degrade Tnnt2a in all cardiomyocytes. Using single-cell transcriptomics, we find that Tnnt2a depletion leads to cardiac phenotypes similar to those observed in tnnt2a mutants, with a loss of blood and pericardial flow-dependent cell types. Furthermore, we achieve conditional degradation of Tnnt2a-eGFP by splitting the zGRAD protein into two fragments that, when combined with the cpFRB2-FKBP system, can be reassembled upon rapamycin treatment. Thus, this Tnnt2a degradation line enables non-invasive control of cardiac contractions with high spatial and temporal specificity and will help further understand how they shape organ development and homeostasis.

Investigating clot-flow interactions by integrating intravital imaging with in silico modeling for analysis of flow, transport, and hemodynamic forces

As a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unified in silico framework to quantify the dynamic clot-flow interactions. We outline the development of the methodology referred to as Intravital Integrated In Silico Modeling or IVISim, and then demonstrate the method on a sample set of simulations comprising clot formation following laser injury in two mouse cremaster arteriole injury model data: one wild-type mouse case, and one diYF knockout mouse case. Simulation predictions are verified against experimental observations of transport of caged fluorescent Albumin (cAlb) in both models. Through these simulations, we illustrate how the IVISim methodology can provide insights into hemostatic processes, the role of flow and clot-flow interactions, and enable further investigations comparing and contrasting different biological model scenarios and parameter variations.

Inter-study reproducibility of cardiovascular magnetic resonance-derived hemodynamic force assessments

Cardiovascular magnetic resonance (CMR)-derived hemodynamic force (HDF) analyses have been introduced recently enabling more in-depth cardiac function evaluation. Inter-study reproducibility is important for a widespread clinical use but has not been quantified for this novel CMR post-processing tool yet. Serial CMR imaging was performed in 11 healthy participants in a median interval of 63 days (range 49–87). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, diastolic deceleration as well as atrial thrust acceleration forces. Inter-study reproducibility and study sample sizes required to demonstrate 10%, 15% or 20% relative changes of HDF measurements were calculated. In addition, intra- and inter-observer analyses were performed. Intra- and inter-observer reproducibility was excellent for all HDF parameters according to intraclass correlation coefficient (ICC) values (> 0.80 for all). Inter-study reproducibility of all HDF parameters was excellent (ICC ≥ 0.80 for all) with systolic parameters showing lower coeffients of variation (CoV) than diastolic measurements (CoV 15.2% for systolic impulse vs. CoV 30.9% for atrial thrust). Calculated sample sizes to detect relative changes ranged from n = 12 for the detection of a 20% relative change in systolic impulse to n = 200 for the detection of 10% relative change in atrial thrust. Overall inter-study reproducibility of CMR-derived HDF assessments was sufficient with systolic HDF measurements showing lower inter-study variation than diastolic HDF analyses.

Reliability of left ventricular hemodynamic forces derived from feature-tracking cardiac magnetic resonance.

Hemodynamic forces (HDF) analysis has been proposed as a method to quantify intraventricular pressure gradients, however data on its reliability are still scanty. Thus, the aim of this study is to assess the reliability of HDF parameters derived from cardiac magnetic resonance (CMR). CMR studies of 25 athletes were analysed by two independent observers and then re-analysed by the same observer one week apart. Intraclass Correlation Coefficient (ICC [95% CI]) and Bland-Altman plots were used to assess association, agreement, and bias of the longitudinal (A-B) HDF, transverse (L-S) HDF, and Impulse Angle. The sample size required to detect a relative change in the HDF parameters was also calculated. In terms of inter-observer variability, there was a good correlation for the A-B and L-S (ICC 0.85 [0.67-0.93] and 0.86 [0.69-0.94]; p<0.001 for both, respectively) and a moderate correlation for the Impulse Angle (ICC 0.73 [0.39-0.87]; p = 0.001). For intra-observer variability, A-B and L-S showed excellent correlation (ICC 0.91 [0.78-0.93] and 0.93 [0.83-0.97]; p<0.001 for both, respectively). Impulse Angle presented good correlation (ICC 0.80 [0.56-0.90]; p<0.001). Frame selection and aortic valve area measurements were the most vulnerable step in terms of reliability of the method. Sample size calculation to detect relative changes ranged from n = 1 to detect a 15% relative change in Impulse Angle to n = 171 for the detection of 10% relative change in A-B HDF. The results of this study showed a low inter- and intra-observer variability of HDF parameters derived from feature-tracking CMR. This provides the fundamental basis for their use both in research and clinical practice, which could eventually lead to the detection of significant changes at follow-up studies.

Impact of left ventricular hemodynamic forces in adult patients with treated aortic coarctation and preserved left ventricular systolic function.

The LV myocardial strain and hemodynamic forces (HDFs) are innovative markers of LV function. Aortic coarctation is safely repaired in infancy; however, mortality and morbidity remain increased in later life. The study investigated the role of left ventricular myocardial deformation and HDFs in asymptomatic patients who underwent successful aortic coarctation repair. Clinical and echocardiographic data were analyzed from 42 repaired CoA, 32±20 years after surgery, 2D echocardiographic global longitudinal strain (GLS), circumferential strain (GCS) and HDFs were determined. CoA patients were compared with 42 patients affected by blood hypertension and 84 healthy controls; all matched for age and gender. All groups had normal LV ejection fraction (LVEF), dimensions, and volumes. CoA patients showed a significantly higher rate of LV mass indexed (p< .001) and left atrial volumes indexed (p< .001). LV myocardial and endocardial global longitudinal and circumferential strain were decreased in CoA patients (p< .001, p< .001; p= .032 and p< .001, respectively). HDF parameters such as LV longitudinal force, LV systolic longitudinal force and LV impulse (LVim) were uniformly reduced (p= .006, p= .001, and p= .001, respectively). LV myocardial strain and HDF parameter values were independently associated with hospitalization for heart failure on univariable Cox regression analysis. Despite preserved LVEF, patients with CoA had lower LV myocardial strain and HDF parameters values, independently associated with hospitalization for heart failure.

Hemodynamics During Development and Postnatal Life.

A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases.

Relation between hemodynamic force, displacement, and the recurrence of coils after coil embolization for cerebral aneurysms: A pilot study

Relation between hemodynamic force, displacement, and the recurrence of coils after coil embolization for cerebral aneurysms: A pilot study

Kiosk 2R-TA-04 - Left Ventricular Hemodynamic Force Assessment by Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy

Kiosk 2R-TA-04 - Left Ventricular Hemodynamic Force Assessment by Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy

Kiosk 4R-TB-10 - Left Ventricular Hemodynamic Forces Comparison of Cine Images and 4D Flow MRI in Patients with Precapillary Pulmonary Hypertension

Kiosk 4R-TB-10 - Left Ventricular Hemodynamic Forces Comparison of Cine Images and 4D Flow MRI in Patients with Precapillary Pulmonary Hypertension

Kiosk 3R-TB-08 - Altered Right and Left Ventricular Hemodynamic Force in Pediatric Pulmonary Hypertension Patients as an Early Indicator of Ventricular Dysfunction

Kiosk 3R-TB-08 - Altered Right and Left Ventricular Hemodynamic Force in Pediatric Pulmonary Hypertension Patients as an Early Indicator of Ventricular Dysfunction

Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes

Background and aimsCoronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. MethodsProspective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. ResultsOne hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56–0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30–0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6–24.3] vs. 7.03 [4.8–11.7] Pa, p < 0.001) and TSVI (163.9 [117.6–249.2] vs. 76.8 [23.1–140.9] m−1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00–1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19–9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11–7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). ConclusionsFocal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. Clinical trial registrationhttps://clinicaltrials,gov/ct2/show/NCT03782688

Blood Clots Are Mechanically Weak in Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) causes a hypercoagulable state characterized by frequent thrombotic sequelae including pulmonary embolism (PE) (Connes et al. Blood. Rev. 2016). Although the coagulation cascade is well characterized in SCD, the engineering-based, biomechanical structural properties of sickle blood clots are poorly understood. Furthermore, the role of clot mechanics in both traditional thrombotic disease manifestations (in situ blood clot, PE) but also common sickle cell related sequelae (pain, stroke) is unknown. Since blood clot embolization is inherently a mechanical process, where clots embolize or “fracture” when hemodynamic forces exceed the internal “strength” of the clot (Tutwiler et al. Sci. Adv. 2020), we submit that investigating the mechanical properties of sickle cell blood clots will reveal insights into the disease-specific factors at play. We hypothesize that SCD clots are not only structurally abnormal, but that this abnormality informs an increased propensity for clot embolization and causes severe vascular complications. Methods: Under the guidance and approval of the IRB, we acquired venipuncture-derived human blood samples from 10 healthy control subjects (14.3±0.9 g/dL Hgb) and 10 patients with sickle cell disease (7 HbSS, 2 HbSC, 1 HbS beta; 10.5±2.3 g/dL Hgb). We coagulated blood into 3D-printed molds designed for uniaxial extension on our mechanical testing machine, see figure 1. To do so, we added calcium chloride to a concentration of 20mM to reverse the ACD anticoagulant and incubated samples for 60 minutes at 37°C and atmospheric oxygen conditions (Sugerman et al. Curr. Protoc. 2021). Samples were then mounted to our tensile testing machine (Instron, Norwood, MA, USA) and two tests were conducted: extension-to-failure in a simple pure shear geometry and in a mode-I fracture geometry. From this data, we calculated various mechanical metrics by quantifying the structural abnormalities and propensity for embolization of SCD blood clots. Results and Conclusion: We primarily compared the stiffness and fracture toughness of sickle cell and healthy blood clots. Stiffness measures how the blood clot deforms in response to force, while fracture toughness measures whether a blood clot is strong or weak (i.e its resistance to rupture). The measured stiffness of SCD clots is 7.27±1.68 kPa, which is significantly higher than the stiffness of healthy clots, 5.22±1.09 kPa (p &amp;lt; 0.001). Additionally, the blood from SCD patients makes clots with a fracture toughness of 2.91±0.85 J/m 2, which is significantly lower than the fracture toughness of healthy clots, 4.43±1.11 J/m 2 (p &amp;lt; 0.0001), see figure 2. The high stiffness of sickle cell blood clots suggests that they are more resistant to deformation than healthy clots. However, the low fracture toughness of sickle cell blood clots suggests that they are more likely to break or embolize when compared to healthy clots. In other words, sickle blood clots exhibit mechanical properties similar to ceramic which has high stiffness and low toughness as opposed to leather (low stiffness, high toughness) or diamond (high stiffness, high toughness). In conclusion, our biomechanical findings of higher stiffness and lower toughness in sickle blood clots are well aligned with established rheological data showing that SCD red blood cells are less deformable than healthy red blood cells (Lu et al. Exp. Biol. Med. 2020). That is, the low deformability of red blood cells in SCD is apparent even at the clot level, which may inform novel disease mechanisms. The sickle cell related determinants of these biomechanical abnormalities, their role in clinical outcomes (PE, pain and stroke) and their response to therapy is the object of future study.

Comparison of endothelial shear stress between ultrathin strut bioresorbable polymer drug-eluting stent vs durable-polymer drug-eluting stent post-stent implantation: An optical coherence tomography substudy from BIOFLOW II

BackgroundRecent clinical data indicate a different performance of biodegradable polymer (BP)-drug eluting stent (DES) compared to durable polymer (DP)-DES. Whether this can be explained by a beneficial impact of BP-DES stent design on the local hemodynamic forces distribution remains unclear. ObjectivesTo compare endothelial shear stress (ESS) distribution after implantation of ultrathin (us) BP-DES and DP-DES and examine the association between ESS and neointimal thickness (NIT) distribution in the two devices at 9 months follow up. Methods and resultsWe retrospectively identified patients from the BIOFLOW II trial that had undergone OCT imaging. OCT data were utilized to reconstruct the surface of the stented segment at baseline and 9 months follow-up, simulate blood flow, and measure ESS and NIT in the stented segment. The patients were divided into 3 groups depending on whether DP-DES (N = 8, n = 56,160 sectors), BP-DES with a stent diameter of >3 mm (strut thickness of 80 μm, N = 6, n = 36,504 sectors), or BP-DES with a stent diameter of ≤3 mm (strut thickness of 60 μm, N = 8, n = 50,040 sectors) were used for treatment. The ESS, and NIT distribution and the association of these two variables were estimated and compared among the 3 groups. ResultsIn the DP-DES group mean NIT was 0.18 ± 0.17 mm and ESS 1.68 ± 1.66 Pa; for the BP-DES ≤3 mm group the NIT was 0.17 ± 0.11 mm and ESS 1.49 ± 1.24 Pa and for the BP-DES >3 mm group 0.20 ± 0.23 mm and 1.42 ± 1.24 Pa respectively (p < 0.001 for both NIT and ESS comparisons across groups). A negative correlation between NIT and baseline ESS was found, the correlation coefficient for all the stented segments was −0.33, p < 0.001. ConclusionIn this OCT sub-study of the BIOFLOW II trial, the NIT was statistically different between groups of patients treated with BP-DES and DP-DES. In addition, regions of low ESS were associated with increased NIT in all studied devices.

Association of echocardiography-derived hemodynamic force parameters with left ventricular reverse remodeling after cardiac resynchronization in non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) improves outcome in selected heart failure patients and can induce left ventricular (LV) reverse remodeling. Echocardiography-derived hemodynamic forces (HDF) are a new clinical tool which provides insight in fluid dynamics. Purpose To evaluate whether baseline HDF parameters are associated with LV reverse remodeling at six months after CRT implantation in patients with non-ischemic cardiomyopathy. Methods From a CRT database, patients with LV ejection fraction &amp;lt;35%, QRS duration &amp;gt;130ms and left bundle branch block were included. At baseline, the following HDF parameters were measured for the complete heart cycle (Figure 1): 1) apical-basal strength, representing the magnitude of the longitudinal HDF, 2) lateral-septal strength, representing the magnitude of the transversal HDF and 3) the angle, representing the HDF orientation. In the systolic thrust (i.e. the positive part of systole in the apical-basal curve), the apical-basal impulse (AB impulse) and the systolic angle were measured. LV reverse remodeling was defined as a reduction of LV end-systolic volume ≥15% at six months. Results In total, 196 patients were included (age 64±11 years, 62% male). LV reverse remodeling was observed in 136 (69%) patients (i.e. responders). Baseline characteristics are presented in Table 1. Responders had a higher angle in the complete heart cycle (67.1 vs 64.1; p = 0.002) as compared to non-responders, indicating less deviation of HDF orientation in responders. Responders also had a higher AB impulse (5.0% vs. 3.4%, p = 0.012) and higher systolic angle (74.0 vs. 71.0), p&amp;lt;0.001), indicating larger magnitude of HDF and less deviation of HDF orientation in the systolic thrust. Univariable logistic regression showed a significant association of loop diuretic use, LV global longitudinal strain (LV GLS), left atrial volume index (LAVI), the angle, AB impulse and the systolic angle with LV reverse remodeling. To minimize collinearity, two multivariable models were built. Loop diuretic use, LV GLS, LAVI and AB impulse were inserted in both models, while the angle was inserted in the first model and the systolic angle in the second model. In the first model, the angle (HR 1.082 (95%CI 1.018, 1.150), p = 0.011) was independently associated with LV reverse remodeling while the systolic angle (HR 1.073 (95%CI 1.011, 1.140), p = 0.021) was independently associated with LV reverse remodeling in the second model. Conclusion At baseline, responders have better orientation of HDF in the complete heart cycle and larger magnitude and better orientation of HDF in the systolic thrust as compared to non-responders. The orientation of HDF in the complete heart cycle and systolic thrust is independently associated with LV reverse remodeling. As such, the angle and systolic angle of HDF have the potential to identify patients that are likely to experience LV reverse remodeling after CRT.Figure 1.HDF in non-ischemic CMPTable 1.Baseline characteristics

Non-obstructive hypertrophic cardiomyopathy exhibit subclinical abnormalities in systolic and diastolic ventricular kinetic energy and systolic haemodynamic forces on 4D flow CMR

Abstract Background Patients with non-obstructive hypertrophic cardiomyopathy (nHCM) exhibit a range of anatomical variations including septal, reverse septal, apical, and concentric hypertrophy. Cardiovascular magnetic resonance imaging (CMR) with 4D flow permits assessment of haemodynamic forces (HDF) and kinetic energy (KE) of intraventricular blood flow (1,2). These parameters may indicate subclinical flow inefficiencies which may not be detectable on routine transthoracic echocardiography (3,4). The aim of this study was therefore to investigate if left ventricular (LV) HDF and KE differ between nHCM and controls, and between subgroups of nHCM. Methods Patients with nHCM (n=71) and age- and sex-matched controls (n=20) underwent CMR at 3T (Trio, Siemens) (Table 1). Patients were categorised as phenotype positive (P+) based on presence of hypertrophy (maximum wall thickness ≥15mm, or ≥13mm with a positive family history), and as phenotype negative (P-) referring to pre-hypertrophic sarcomeric variant carriers. Patients with P+ nHCM were classified into subgroups based on the pattern of hypertrophy. Left ventricular HDF and KE were computed over the cardiac cycle using validated modules (1) (Figure 1). Measurements of HDF were based on the Navier-Stokes equations (1), and analysed in three orthogonal directions as root mean square and peak values for systole and diastole. Force ratio was calculated as the sum of the two transverse components divided by the longitudinal component. The Mann-Whitney U test was used for group comparisons, Pearson analysis for correlations, and Fisher’s exact test for binary categorical data. Results P+, P- patients and controls had comparable LV ejection fraction from CMR, LV outflow tract pressure gradients, and diastolic parameters on echocardiography (Table 1). Systolic HDF and force ratio were increased, primarily in the lateral wall-septum direction in septal and reverse septal P+ patients compared to controls, but did not differ in any other directions in P+ compared to P- patients and to controls (Table 1, Figure 1). Diastolic HDF and force ratio did not differ between groups. Systolic KE was increased in P+ patients compared to P- and to controls (Table 1, Figure 1), mainly through increased KE in patients with septal and reverse septal hypertrophy. P+ patients also had increased late diastolic (A-wave) KE relative to P- patients and to controls (Table 1). Both systolic KE and force ratio correlated with maximum wall thickness in patients (r=0.31, p=0.005; r=0.43, p&amp;lt;0.0001). Conclusion In non-obstructive hypertrophic cardiomyopathy, left ventricular HDF and KE analysis from 4D flow CMR detect subclinical flow abnormalities. Increased systolic HDF and KE are linked to the extent and pattern of hypertrophy. Late diastolic A-wave KE was also abnormal in P+ patients despite normal diastolic velocities on echocardiography.Table 1Figure 1

Hemodynamic forces from 4D flow magnetic resonance imaging for optimised prediction of cardiac resynchronisation therapy outcome

Abstract Background Patients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronisation therapy (CRT), but many patients have limited treatment response (1). The use of imaging to optimise patient selection has been repeatedly attempted with some success (2), and scar detected on late gadolinium enhancement (LGE) imaging has been associated with reduced response rates (3). Intraventricular hemodynamic force (HDF) analysis has been suggested as a novel marker for assessment of patients eligible for CRT (4). The aim of this study was therefore to investigate if septal scar from LGE or left ventricular HDF computed from cardiac magnetic resonance (CMR) imaging can improve prediction of CRT outcome. Methods Patients with heart failure, EF&amp;lt;35% and LBBB (n=22) underwent CMR with 4D flow at 1.5T or 3T (Achieva, Philips Healthcare) prior to CRT (Figure 1). Scar was assessed by LGE. Left ventricular HDF were computed based on the Navier-Stokes equations, using a validated module in the software Segment v3.3 R10057 (Medviso, Lund, Sweden) (5). Forces (N) were analysed in three orthogonal directions as root mean square (RMS) and peak values, reported in median [interquartile range]. Transversal/longitudinal HDF ratio was calculated for systole and diastole. Echocardiography was performed before and six months after CRT, and patients with end-systolic volume reduction ≥15% at follow-up were defined as responders. The Mann-Whitney U test was used for group comparisons, Fisher’s exact test for binary categorical data, Wilcoxon test for paired comparisons, and receiver operating characteristic analysis for prediction of CRT response. Results There was no difference between responders and non-responders in LGE (Table 1). Non-responders had smaller HDF than responders in the inferior-anterior direction in systole (RMS: 0.055 [0.027] vs 0.070 [0.032], p=0.04; peak: 0.11 [0.069] vs 0.15 [0.083], p=0.03), and in the apex-base direction in diastole (RMS: 0.087 [0.018] vs 0.11 [0.046], p=0.047). Non-responders had larger diastolic HDF ratio than responders (RMS: 0.89 [0.45] vs 0.67 [0.20], p=0.004; peak: 1.1 [0.51] vs 0.57 [0.40], p=0.01) (Figure 1). Receiver operating characteristic analysis of diastolic HDF ratio found an area under the curve of 0.88 (p=0.005). Identification of non-responders using diastolic HDF ratio with a specificity of 100%, resulted in a ratio of &amp;gt;0.87 for non-responders, with a sensitivity of 57%. Intragroup comparison found higher HDF ratio in systole than diastole for responders but not for non-responders (Figure 1). Conclusions Prediction of left ventricular remodelling following CRT may be optimized by hemodynamic force analysis from 4D flow CMR, while septal scar from LGE was not found indicative of CRT outcome in this pilot study. Larger-scale studies are required before clinical implementation of HDF analysis.Table 1Figure 1

Hemodynamic forces analysis using transthoracic echocardiogram in acute heart failure

Abstract Introduction Heart failure (HF) represents a major health problem, being one of the leading causes of hospitalization. At present, echocardiography plays a key role in HF diagnosis and many innovations have been made. Particularly, in the last decades attention was directed towards fluid dynamic study, as it seems to better predict ventricular dysfunction. Therefore, the concept of hemodynamic forces (HDF) was introduced. Purpose The aim of our study was to evaluate HDF in patients with acute HF in the setting of the Emergency Room and at the time of recovery, furthermore, comparing them with healthy volunteers. Patients were also contacted 30 days after discharge in order to evaluate whether there had been new hospital admissions. Methods We enrolled 132 patients, of whom only 14 were effectively recruited given the need for the presence of sinus rhythm and the absence of severe valvulopathies. These patients were compared with 8 healthy volunteers. All individuals underwent trans-thoracic echocardiography, in order to assess cardiac morphology and function. HDF analysis was performed using QStrain software. Results The graphical presentation of HDF analysis differed in a statistically significant manner between patients with acute HF and healthy volunteers, with the first group showing a lower systolic peak (7.66% [6.32;14.3] vs 21.6 % [18.4;26.7]; p 0.003) and a shorter diastolic time (372 msec [342;472] vs 631 msec [468;679]; p = 0.012). Moreover, in patients with HF we identified a statistically significant reduction of the Inward Displacement (ID), a recently introduced parameter of systolic function, (12667 [10404;22647] vs 27289 [25131;29001]; p 0.003) and an increased systolic ratio, consisting of the ratio between transverse and apical-basal HDF (23.6±10.9 in HF patients vs 17.5±5.60 in healthy subjects; p = 0.102). Comparing patients with HF in the acute phase and at the time of recovery, we couldn’t obtain statistically significant results due to the small sample size. However, considering case by case, we pointed out a difference in ID and in systolic ratio which seemed to better identify effective hemodynamic stability compared with Ejection Fraction (EF) and Global Longitudinal Strain (GLS). Conclusion Our study appears to be the first one to evaluate HDF in the setting of acute HF. Our results suggest how HDF analysis could be a useful tool improving HF management, particularly leading to a better identification of effective hemodynamic compensation. However, we also emphasized the limitations of this tool, which currently restrict its use to the outpatient setting, particularly in the field of research.