Hemodynamic Load Research Articles

Effects of septal myectomy on left atrial and left ventricular function in obstructive hypertrophic cardiomyopathy.

Mechanical function of the left atrium (LA) and the left ventricle (LV) has been demonstrated to be a prognostic factor in patients with hypertrophic cardiomyopathy (HCM). We explore whether myocardial mechanical function can be improved by septal reduction therapy in symptomatic obstructive HCM. Among 65 patients who underwent septal myectomy for symptomatic obstructive HCM from 2006 to 2022, 44 were analysed after excluding those who underwent simultaneous valve repair or replacement or maze operation. LA and LV functional variables including LA strain and LV global longitudinal strain were evaluated by two-dimensional and speckle-tracking echocardiography and compared before and 1year after surgery. After septal myectomy, LA volume index (58.1±18.3 vs. 45.3±14.6mL/m2 , P=0.001) decreased significantly. As LV end-systolic dimension increased after surgery, the LV ejection fraction decreased (73.8±6.7 vs. 62.9±8.3%, P<0.001). LA strain (24.4±9.3 vs. 30.5±13.6%, P=0.004) improved after septal myectomy, but LV global longitudinal strain deteriorated (-12.6±3.6 vs. -11.6±4.3%, P=0.033), mainly related to worsening non-septal longitudinal strain (-14.4±4.3 vs. -10.9±8.4%, P=0.005). As haemodynamic loads due to LV outflow tract obstruction was relieved through surgical septal reduction therapy in patients with symptomatic obstructive HCM, there was a significant reduction in LA volume and restoration of LA mechanical dysfunction. However, LV mechanical dysfunction deteriorated even after surgical septal reduction therapy.

Diastolic function in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by clustered age-independent concentric left ventricular (LV) geometry, geometry-independent systolic dysfunction and age and heart rate-independent diastolic dysfunction. Concentric LV geometry is always associated with echocardiographic markers of abnormal LV relaxation and increased myocardial stiffness, two hallmarks of diastolic dysfunction. Non-haemodynamic mechanisms such as metabolic and electrolyte abnormalities, activation of biological pathways and chronic exposure to cytokine cascade and the myocardial macrophage system also impact myocardial structure and impair the architecture of the myocardial scaffold, producing and increasing reactive fibrosis and altering myocardial distensibility. This review addresses the pathophysiology of diastole in CKD and its relations with cardiac mechanics, haemodynamic loading, structural conditions, non-haemodynamic factors and metabolic characteristics. The three mechanisms of diastole will be examined: elastic recoil, active relaxation and passive distensibility and filling. Based on current evidence, we briefly provide methods for quantification of diastolic function and discuss whether diastolic dysfunction represents a distinct characteristic in CKD or a proxy of the severity of the cardiovascular condition, with the potential to be predicted by the general cardiovascular phenotype. Finally, the review discusses assessment of diastolic function in the context of CKD, with special emphasis on end-stage kidney disease, to indicate whether and when in-depth measurements might be helpful for clinical decision making in this context.

Left Atrial Ligation in the Avian Embryo as a Model for Altered Hemodynamic Loading During Early Vascular Development.

Due to its four-chambered mature ventricular configuration, ease of culture, imaging access, and efficiency, the avian embryo is a preferred vertebrate animal model for studying cardiovascular development. Studies aiming to understand the normal development and congenital heart defect prognosis widely adopt this model. Microscopic surgical techniques are introduced to alter the normal mechanical loading patterns at a specific embryonic time point and track the downstream molecular and genetic cascade. The most common mechanical interventions are left vitelline vein ligation, conotruncal banding, and left atrial ligation (LAL), modulating the intramural vascular pressure and wall shear stress due to blood flow. LAL, particularly if performed in ovo, is the most challenging intervention, with very small sample yields due to the extremely fine sequential microsurgical operations. Despite its high risk, in ovo LAL is very valuable scientifically as it mimics hypoplastic left heart syndrome (HLHS) pathogenesis. HLHS is a clinically relevant, complex congenital heart disease observed in human newborns. A detailed protocol for in ovo LAL is documented in this paper. Briefly, fertilized avian embryos were incubated at 37.5 °C and 60% constant humidity typically until they reached Hamburger-Hamilton (HH) stages 20 to 21. The egg shells were cracked open, and the outer and inner membranes were removed. The embryo was gently rotated to expose the left atrial bulb of the common atrium. Pre-assembled micro-knots from 10-0 nylon sutures were gently positioned and tied around the left atrial bud. Finally, the embryo was returned to its original position, and LAL was completed. Normal and LAL-instrumented ventricles demonstrated statistically significant differences in tissue compaction. An efficient LAL model generation pipeline would contribute to studies focusing on synchronized mechanical and genetic manipulation during the embryonic development of cardiovascular components. Likewise, this model will provide a perturbed cell source for tissue culture research and vascular biology.

Persistent non-homeostatic remodeling of aortic collagen following a brief episode of hypertension: A computational study

The healthy adult aorta exhibits a remarkable homeostatic ability to respond to sustained changes in hemodynamic loads under many circumstances, but this mechanical homeostasis can be compromised or lost in natural aging and diverse pathological processes. Herein, we investigate persistent non-homeostatic changes in the composition and mechanical properties of the thoracic aorta in adult wild-type mice following 14 days of angiotensin II-induced hypertension. We employ a multiscale computational model of arterial growth and remodeling driven by mechanosensitive and angiotensin II-related cell signaling pathways. We find that experimentally observed findings can only be recapitulated computationally if the collagen deposited during the transient period of hypertension has altered properties (deposition stretch, fiber angle, crosslinking) compared with the collagen produced in the original homeostatic state. Some of these changes are predicted to persist for at least six months after blood pressure is restored to normal levels, consistent with the experimental findings.

MATERNAL LEFT VENTRICULAR ADAPTATION IN TWIN PREGNANCY

Objective: During pregnancy, a maternal left ventricular (LV) remodeling occurs to face significant hemodynamic changes. Although twin pregnancy can require greater modifications than in singleton, limited data are currently available. The aim of the study was to longitudinally investigate maternal changes of LV function and compliance in twin pregnancy. Design and method: 35 uncomplicated twin pregnancy women underwent transthoracic echocardiography at first (T1, 10-15 weeks) and third trimester (T3, 30-35 weeks) of gestation. Left atrial (LA) and LV dimensions, LV volumes, systolic and diastolic function were measured, LV mass was calculated. Speckle-tracking imaging was used to evaluate global longitudinal strain (GLS). Non-invasive pressure-volume curves (PV loops) were reconstructed using a dedicated software. Results: Maternal LA and LV dimensions, LV volumes and mass increased from T1 to T3. Ejection fraction and GLS showed no changes between visits. Assessment of diastolic function (at pulsed wave Doppler and tissue Doppler) showed no changes in E/A ratio, while E/e’ ratio was higher at T3. At PV loops analysis, ventricular-arterial coupling (VAC) was stable due to the reduction of both LV end-systolic elastance (Ees) and arterial elastance (Ea). An increase in stroke work was observed. The increase in LV end-diastolic volumes from T1 to T3 with no changes in LV end-diastolic filling pressure suggested enhanced LV cavity compliance (rightward shift of the end-diastolic pressure-volume relationship, EDPVR). Conclusions: Maternal heart in uncomplicated twin pregnancy adapts to the increased hemodynamic load with an increase in stroke work and enhancement of LV volumes without altering ventricular filling pressure.

Enhancement of left ventricular compliance in twin pregnancy

Abstract Funding Acknowledgements Type of funding sources: None. Background The knowledge of maternal left ventricular adaptation in twin pregnancies is incomplete. Purpose The objective of this study was to longitudinally investigate maternal changes of left ventricular (LV) function and compliance in twin pregnancies. Methods Thirty-five women (age 35.3±4.8 years) with uncomplicated twin pregnancy were enrolled to undergo transthoracic echocardiography at 10-15 (T1) and 30-38 (T3) week’s gestation. Left atrial (LA) and LV dimensions, LV volumes and mass, diastolic parameters (at pulsed wave Doppler and tissue Doppler), global longitudinal strain (GLS) at speckle-tracking imaging, and non-invasive pressure-volume curves (PV loops) were measured and calculated. Results Maternal LA and LV dimensions, LV volumes and mass had an increasing trend from T1 to T3 (p&amp;lt;0.001 for all). E/A remained stable, while E/e’ ratio slightly increased during gestation. GLS showed no changes between the two visits. At PV loops analysis (Figure 1), LV end-systolic elastance (Ees) and arterial elastance (Ea) both decreased, with no changes in ventricular-arterial coupling (VAC). LV end-diastolic volumes increased from T1 to T3 with no changes in LV end-diastolic filling pressure; the rightward shift of the end-diastolic pressure-volume relationship (EDPVR) suggested enhanced LV cavity compliance (Figure 2). An increase in stroke work was observed. Conclusions During twin pregnancy GLS and VAC were not modified showing functional adaptation to enhanced haemodynamic load. Importantly, stroke work increase was sustained by enhancement in LV end-diastolic volume with unaltered filling pressure.

New Approaches in Heart Research: Prevention Instead of Cardiomyoplasty?

Cardiovascular diseases are the leading cause of death in industrialized nations. Due to the high number of patients and expensive treatments, according to the Federal Statistical Office (2017) in Germany, cardiovascular diseases account for around 15% of total health costs. Advanced coronary artery disease is mainly the result of chronic disorders such as high blood pressure, diabetes, and dyslipidemia. In the modern obesogenic environment, many people are at greater risk of being overweight or obese. The hemodynamic load on the heart is influenced by extreme obesity, which often leads to myocardial infarction (MI), cardiac arrhythmias, and heart failure. In addition, obesity leads to a chronic inflammatory state and negatively affects the wound-healing process. It has been known for many years that lifestyle interventions such as exercise, healthy nutrition, and smoking cessation drastically reduce cardiovascular risk and have a preventive effect against disorders in the healing process. However, little is known about the underlying mechanisms, and there is significantly less high-quality evidence compared to pharmacological intervention studies. Due to the immense potential of prevention in heart research, the cardiologic societies are calling for research work to be intensified, from basic understanding to clinical application. The topicality and high relevance of this research area are also evident from the fact that in March 2018, a one-week conference on this topic with contributions from top international scientists took place as part of the renowned "Keystone Symposia" ("New Insights into the Biology of Exercise"). Consistent with the link between obesity, exercise, and cardiovascular disease, this review attempts to draw lessons from stem-cell transplantation and preventive exercise. The application of state-of-the-art techniques for transcriptome analysis has opened new avenues for tailoring targeted interventions to very individual risk factors.

Central Hemodynamic Response to Activation of the Vestibular Sympathetic Reflex with Head Down Rotation in Healthy Young Adults.

The purpose of this study was to assess the effect of vestibular-sympathetic activation on estimated measures of central (aortic) hemodynamic load in young adults. Methods: 31 participants (n=14 female, 17 male) underwent radial tonometry and popliteal Doppler-ultrasound in the prone position with the head in a neutral position and during 10 minutes of head-down rotation (HDR) as a means of activating the vestibular sympathetic reflex. Subjective orthostatic intolerance was assessed utilizing a 10-item orthostatic hypotension questionnaire. Results: There was a reduction in brachial systolic BP during HDR (111±10 vs. 109±9 mmHg, p<0.05), but there was no change in aortic systolic BP (100±9 vs. 99±8 mmHg, p>0.05). Aortic augmentation index (-5±11 vs. -12±12%, p<0.05) and reservoir pressure (28±8 vs. 26±8mmHg, p<0.05) were reduced with a concomitant reduction in popliteal conductance (5.6±0.7 vs. 4.5±0.7 ml/min∙mmHg, p<0.05). Change in aortic systolic BP was associated with subjective orthostatic intolerance score (r = -0.39, p<0.05). Conclusions: Activation of the vestibular sympathetic reflex via HDR resulted in slight reductions in brachial BP concomitant with preservation of aortic BP. Despite peripheral vascular constriction during HDR, there was a reduction in pressure from wave reflections and reservoir pressure. Finally, there was an association between change in aortic systolic BP during HDR and orthostatic intolerance score suggesting that individuals that cannot defend against drops in aortic BP during vestibular sympathetic reflex activation may be more likely to experience higher subjective symptomatology of orthostatic intolerance.

Transvalvular Unloading Mitigates Ventricular Injury Due to Venoarterial Extracorporeal Membrane Oxygenation in Acute Myocardial Infarction

Whether extracorporeal membrane oxygenation (ECMO) with Impella, known as EC-Pella, limits cardiac damage in acute myocardial infarction remains unknown. The authors now report that the combination of transvalvular unloading and ECMO (EC-Pella) initiated before reperfusion reduced infarct size compared with ECMO alone before reperfusion in a preclinical model of acute myocardial infarction. EC-Pella also reduced left ventricular pressure-volume area when transvalvular unloading was applied before, not after, activation of ECMO. The authors further observed that EC-Pella increased cardioprotective signaling but failed to rescue mitochondrial dysfunction compared with ECMO alone. These findings suggest that ECMO can increase infarct size in acute myocardial infarction and that EC-Pella can mitigate this effect but also suggest that left ventricular unloading and myocardial salvage may be uncoupled in the presence of ECMO in acute myocardial infarction. These observations implicate mechanisms beyond hemodynamic load as part of the injury cascade associated with ECMO in acute myocardial infarction.

Myocardial Fatigue at a Glance.

Expanding on the modern lexicon of heart failure (HF), the novel mechano-energetic concept of myocardial fatigue describes a transiently energy-depleted myocardium with impaired contractility and relaxation in the face of adverse haemodynamic load. It encompasses established concepts of ventricular-arterial decoupling, deranged cardiac energetics and impaired myocardial efficiency, offering an alternative explanation for functional causes of HF.

Hemodynamic performance evaluation of neonatal ECMO double lumen cannula using fluid-structure interaction.

Extra corporeal membrane oxygenation (ECMO) is an artificial oxygenation facility, employed in situations of cardio-pulmonary failure. Some diseases i.e., acute respiratory distress syndrome, pulmonary hypertension, corona virus disease (COVID-19) etc. affect oxygenation performance of the lungs thus requiring the need of artificial oxygenation. Critical care teams used ECMO technique during the COVID-19 pandemic to support the heart and lungs of COVID-19 patients who had an acute respiratory or cardiac failure. Double Lumen Cannula (DLC) is one of the most critical components of ECMO as it resides inside the patient and, connects patient with external oxygenation circuit. DLC facilitates delivery and drainage of blood from the patient's body. DLC is characterized by delicate balance of internal and external flows inside a limited space of the right atrium (RA). An optimal performance of the DLC necessitates structural stability under biological and hemodynamic loads, a fact that has been overlooked by previously published studies. In the past, many researchers experimentally and computationally investigated the hemodynamic performance of DLC by employing Eulerian approach, which evaluate instantaneous blood damage without considering blood shear exposure history (qualitative assessment only). The present study is an attempt to address the aforementioned limitations of the previous studies by employing Lagrangian (quantitative assessment) and incorporating the effect of fluid-structure interaction (FSI) to study the hemodynamic performance of neonatal DLC. The study was performed by solving three-dimensional continuity, momentum, and structural mechanics equation(s) by numerical methods for the blood flow through neonatal DLC. A two-way coupled FSI analysis was performed to analyze the effect of DLC structural deformation on its hemodynamic performance. Results show that the return lumen was the most critical section with maximum pressure drop, velocity, shear stresses, and blood damage. Recirculation and residence time of blood in the right atrium (RA) increases with increasing blood flow rates. Considering the structural deformation hasled to higher blood damage inside the DLC-atrium system. Maximum Von-Mises stress was present on the side edges of the return lumen that showed direct proportionality with the blood flow rate.

24-year-old obese woman with dilated cardiomyopathy: a case report of obese cardiomyopathy

Background: Dilated cardiomyopathy is a disease characterized by enlargement of the heart ventricles with impaired left ventricular or biventricular systolic function. Obesity is a risk factor for changes in the structure and function of the heart, known as obese cardiomyopathy. The purpose of writing this case report is to holistically discuss obesity as a risk factor for dilated cardiomyopathy based on a literature review. Case presentation: A 24-year-old woman complained of shortness of breath 2 months ago, appeared during activities and while she slept at night, and improved when sitting and resting. Other complaints are palpitations, swollen feet, nausea, and vomiting. Childhood history of obesity. Blood pressure 160/95 mmHg, respiratory rate 22 times/minute, and body mass index 33.8 kg/m2 (obesity II). The jugular venous pressure is increased. Auscultation revealed a systolic murmur at ICS 4 grade 3/6 and pulmonary crackles, with pitting edema in the legs. Electrocardiography revealed sinus tachycardia. Laboratory tests showed high triglycerides and total cholesterol, and other laboratories were within normal limits. Echocardiographic examination showed decreased left ventricular systolic function, severe left ventricular dilatation, and an ejection fraction of 27.9%. No significant lesions were found during the angiographic examination. A magnetic resonance imaging examination revealed non-ischemic cardiomyopathy, moderate left ventricular dysfunction, and severe right ventricular dysfunction. Patients were given heart failure therapy according to guidelines. On routine control, the patient's condition was stable. Conclusion: Obesity is believed to be a risk factor for dilated cardiomyopathy through an increased hemodynamic load, neurohormonal dysregulation, inflammation, and lipotoxicity. Modalities such as the electrocardiogram, echocardiography, and magnetic resonance imaging can support the results of examinations for diagnosing dilated cardiomyopathy due to obesity. The management of obese cardiomyopathy involves changing lifestyles and administering drugs according to the clinical manifestations of heart failure.

The indices of the cardiovascular system in workers with different body weights in unfavourable working conditions

Introduction. The cardiovascular system is an integral indicator of the body’s adaptive responses.&#x0D; Goal is a comparative analysis of the function of the cardiovascular system (CVS) in persons with different nutritional status, working on a rotational basis.&#x0D; Materials and methods. Two groups of healthy men were observed: those with normal nutritional status (NNS, n = 14) and those with increased body weight (IBW, n = 13). Working conditions were evaluated according to the degree of harmfulness and danger. The examination was carried out twice: before the start and after 2 months. after shift work. Systolic and diastolic blood pressure, heart rate (HR) were measured. The Robinson index, endurance coefficient, vegetative Kerdo index, and circulatory efficiency coefficient were calculated.&#x0D; Results. Working conditions were characterized by work at night in an open area, irregularity of shifts, unregulated breaks for rest, the influence of noise and vibration. In the initial state, body weight in NNS individuals was 74.1±1.1 kg versus 91.8±2.7 kg (p=0.001) in IBW persons; HR – 60.0±2.3 versus 73.1±2.0 (p=0.001). After shift work, body weight decreased by 22.2% and 50.0% in persons in the comparison groups. Integral indicators indicated a more negative response of the cardiovascular system to working conditions in IBW people: less resistance to stress (eurance coefficient), lower performance (efficiency ratio of blood circulation), a higher level of hemodynamic load (Robinson index), in NNS people there were dominated by parasympathetic influences, 33.3% of IBW persons had sympathetic influences.&#x0D; Limitations. Healthy males working on a rotational basis, with a normal nutritional status and with overweight and obesity.&#x0D; Conclusion. Overweight and obesity negatively affect the cardiovascular system, reducing the functional reserves of the body. Under unfavourable working conditions, the changes are also more pronounced than in the group of people with a normal nutritional status.

Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model.

Right ventricular (RV) failure is the major determinant of outcome in pulmonary hypertension (PH). Calves exposed to 2-wk hypoxia develop severe PH and unlike rodents, hypoxia-induced PH in this species can lead to right heart failure. We, therefore, sought to examine the molecular and structural changes in the RV in calves with hypoxia-induced PH, hypothesizing that we could identify mechanisms underlying compensated physiological function in the face of developing severe PH. Calves were exposed to 14 days of environmental hypoxia (equivalent to 4,570 m/15,000 ft elevation, n = 29) or ambient normoxia (1,525 m/5,000 ft, n = 25). Cardiopulmonary function was evaluated by right heart catheterization and pressure volume loops. Molecular and cellular determinants of RV remodeling were analyzed by cDNA microarrays, RealTime PCR, proteomics, and immunochemistry. Hypoxic exposure induced robust PH, with increased RV contractile performance and preserved cardiac output, yet evidence of dysregulated RV-pulmonary artery mechanical coupling as seen in advanced disease. Analysis of gene expression revealed cellular processes associated with structural remodeling, cell signaling, and survival. We further identified specific clusters of gene expression associated with 1) hypertrophic gene expression and prosurvival mechanotransduction through YAP-TAZ signaling, 2) extracellular matrix (ECM) remodeling, 3) inflammatory cell activation, and 4) angiogenesis. A potential transcriptomic signature of cardiac fibroblasts in RV remodeling was detected, enriched in functions related to cell movement, tissue differentiation, and angiogenesis. Proteomic and immunohistochemical analysis confirmed RV myocyte hypertrophy, together with localization of ECM remodeling, inflammatory cell activation, and endothelial cell proliferation within the RV interstitium. In conclusion, hypoxia and hemodynamic load initiate coordinated processes of protective and compensatory RV remodeling to withstand the progression of PH.NEW & NOTEWORTHY Using a large animal model and employing a comprehensive approach integrating hemodynamic, transcriptomic, proteomic, and immunohistochemical analyses, we examined the early (2 wk) effects of severe PH on the RV. We observed that RV remodeling during PH progression represents a continuum of transcriptionally driven processes whereby cardiac myocytes, fibroblasts, endothelial cells, and proremodeling macrophages act to coordinately maintain physiological homeostasis and protect myocyte survival during chronic, severe, and progressive pressure overload.

Pulmonary artery wedge pressure and left ventricular end-diastolic pressure during exercise in patients with dyspnoea.

Pulmonary artery wedge pressure (PAWP) during exercise, as a surrogate for left ventricular (LV) end-diastolic pressure (EDP), is used to diagnose heart failure with preserved ejection fraction (HFpEF). However, LVEDP is the gold standard to assess LV filling, end-diastolic PAWP (PAWPED) is supposed to coincide with LVEDP and mean PAWP throughout the cardiac cycle (PAWPM) better reflects the haemodynamic load imposed on the pulmonary circulation. The objective of the present study was to determine precision and accuracy of PAWP estimates for LVEDP during exercise, as well as the rate of agreement between these measures. 46 individuals underwent simultaneous right and left heart catheterisation, at rest and during exercise, to confirm/exclude HFpEF. We evaluated: linear regression between LVEDP and PAWP, Bland-Altman graphs, and the rate of concordance of dichotomised LVEDP and PAWP ≥ or < diagnostic thresholds for HFpEF. At peak exercise, PAWPM and LVEDP, as well as PAWPED and LVEDP, were fairly correlated (R2>0.69, p<0.01), with minimal bias (+2 and 0 mmHg respectively) but large limits of agreement (±11 mmHg). 89% of individuals had concordant PAWP and LVEDP ≥ or <25 mmHg (Cohen's κ=0.64). Individuals with either LVEDP or PAWPM ≥25 mmHg showed a PAWPM increase relative to cardiac output (CO) changes (PAWPM/CO slope) >2 mmHg·L-1·min-1. During exercise, PAWP is accurate but not precise for the estimation of LVEDP. Despite a good rate of concordance, these two measures might occasionally disagree.

A multiscale computational framework to evaluate flow alterations during mechanical thrombectomy for treatment of ischaemic stroke.

The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome. In this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments.

Effect of mechanical tension on fibroblast transcriptome profile and regulatory mechanisms of myocardial collagen turnover.

Excess deposition of extracellular matrix in the myocardium is a predictor of reduced left ventricular function. Although reducing the hemodynamic load is known to improve myocardial fibrosis, the mechanisms underlying the reversal of the fibrosis have not been elucidated. We focused on the elasticity of myocardial tissue, which is assumed to influence the fibroblast phenotype. Normal and fibrotic myocardium were cultured in 16 kPa and 64 kPa silicone gel-coated dishes supplemented with recombinant TGFβ protein, respectively. Matrix-degrading myocardium was cultured in 64 kPa silicone gel-coated dishes with recombinant TGFβ protein and then in 16 kPa silicone gel-coated dishes. Cardiac fibroblasts were cultured in this three-part in vitro pathological models and compared. Fibroblasts differentiated into activated or matrix-degrading types in response to the pericellular environment. Comprehensive gene expression analysis of fibroblasts in each in vitro condition showed Selenbp1 to be one of the genes responsible for regulating differentiation of fibroblasts. In vitro knockdown of Selenbp1 enhanced fibroblast activation and inhibited conversion to the matrix-degrading form. In vivo knockdown of Selenbp1 resulted in structural changes in the left ventricle associated with progressive tissue fibrosis and left ventricular diastolic failure. Selenbp1 is involved in regulating fibroblast differentiation and appears to be one of the major molecules regulating collagen turnover in cardiac fibrosis.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Transmural Wave Speed Gradient May Distinguish Intrinsic Myocardial Stiffening From Preload-Induced Changes in Operational Stiffness in Shear Wave Elastography.

Shear wave elastography (SWE) is a promising technique to non-invasively assess myocardial stiffness based on the propagation speed of mechanical waves. However, a high wave propagation speed can either be attributed to an elevated intrinsic myocardial stiffness or to a preload-induced increase in operational stiffness. Our objective was to find a way to discriminate intrinsic myocardial stiffening from stiffening caused by an increased pressure in SWE. We used the finite element method to study the shear wave propagation patterns when stiffness and/or pressure is elevated, compared to normal stiffness and pressure. Numerical findings were verified in a few human subjects. The transmural wave speed gradient was able to distinguish changes in intrinsic stiffness from those induced by differing hemodynamic load (a speed of ±3.2 m/s in parasternal short-axis (PSAX) view was associated with a wave speed gradient of -0.17 ± 0.15 m/s/mm when pressure was elevated compared to 0.04 ± 0.05 m/s/mm when stiffness was elevated). The gradient however decreased when stiffness increased (decrease with a factor 3 in PSAX when stiffness doubled at 20 mmHg). The human data analysis confirmed the presence of a wave speed gradient in a patient with elevated ventricular pressure. Cardiac SWE modeling is a useful tool to gain additional insights into the complex wave physics and to guide post-processing. The transmural differences in wave speed may help to distinguish loading-induced stiffening from intrinsic stiffness changes. The transmural wave speed gradient has potential as a new diagnostic parameter for future clinical studies.

Echocardiographic Evaluation in Paediatric Sickle Cell Disease Patients: A Pilot Study

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens' Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load.