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Annals of Biomedical Engineering May 2021Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases...
Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.
Topics: Aortic Valve Stenosis; Biomechanical Phenomena; Cardiomyopathies; Fetal Heart; Finite Element Analysis; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Models, Cardiovascular; Ultrasonography; Ventricular Function, Left
PubMed: 33175989
DOI: 10.1007/s10439-020-02683-x -
European Journal of Sport Science Oct 2019To investigate the association of electrocardiographic (ECG) left and/or right ventricular hypertrophy (LVH and RVH) with physical fitness of military males.
AIM
To investigate the association of electrocardiographic (ECG) left and/or right ventricular hypertrophy (LVH and RVH) with physical fitness of military males.
METHODS
We used a military cohort of 2587 males, who were on average 29.1 years of age, from the cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) study in Taiwan for the analysis. Isolated ECG-LVH ( = 779) was diagnosed by either the Sokolow-Lyon or Cornell voltage criteria. Isolated ECG-RVH ( = 234) was defined by either the Sokolow-Lyon or Myers et al. voltage criteria. Combined ECG-LVH/RVH ( = 140) was defined as those who met the voltage criteria for both LVH and RVH. The other ECGs were defined as unaffected ( = 1434). Physical fitness was evaluated by the upper and lower 16% exercise performance (beyond 1-standard deviation) in 3000-meter run, 2-minute sit-ups, and 2-minute push-ups. All procedures were standardized and monitored by unified computerized scoring systems. A multiple logistic regression was used to determine the relationship.
RESULTS
Compared with unaffected participants, those with an isolated ECG-LVH were tended to have a better 3000-meter run performance (odds ratio (OR) and 95% confidence intervals: 1.22 [0.99-1.50], -value = 0.064) after adjusting for age, service specialty, body mass index, mean blood pressure, smoking status, alcohol intake, hemoglobin level, and exercise frequency. By contrast, those with an isolated ECG-RVH were tended to have a worse 2-minute sit-up performance (OR: 1.46 [0.99-2.16], -value = 0.054).
CONCLUSION
Military males with ECG-LVH and/or ECG-RVH compared to unaffected participants may have diverse exercise performances. However, these observations narrowly failed to reach statistical significance.
Topics: Adult; Cardiorespiratory Fitness; Electrocardiography; Heart Ventricles; Humans; Male; Military Personnel; Retrospective Studies; Ventricular Remodeling
PubMed: 30955480
DOI: 10.1080/17461391.2019.1595741 -
Circulation. Cardiovascular Imaging Apr 2020
Topics: Aortic Valve Stenosis; Heart Ventricles; Humans; Transcatheter Aortic Valve Replacement
PubMed: 32268806
DOI: 10.1161/CIRCIMAGING.120.010711 -
American Journal of Respiratory Cell... Mar 2021Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in...
Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. MAO-A levels in lung and RV samples from patients with PAH were compared with levels in samples from donors without PAH. Experimental PAH was induced in male Sprague-Dawley rats by using Sugen 5416 and hypoxia (SuHx), and RV failure was induced in male Wistar rats by using pulmonary trunk banding (PTB). Animals were randomized to receive either saline or the MAO-A inhibitor clorgyline at 10 mg/kg. Echocardiography and RV catheterization were performed, and heart and lung tissues were collected for further analysis. We found increased MAO-A expression in the pulmonary vasculature of patients with PAH and in experimental experimental PAH induced by SuHx. Cardiac MAO-A expression and activity was increased in SuHx- and PTB-induced RV failure. Clorgyline treatment reduced RV afterload and pulmonary vascular remodeling in SuHx rats through reduced pulmonary vascular proliferation and oxidative stress. Moreover, clorgyline improved RV stiffness and relaxation and reversed RV hypertrophy in SuHx rats. In PTB rats, clorgyline had no direct clorgyline had no direct effect on the right ventricle effect. Our study reveals the role of MAO-A in the progression of PAH. Collectively, these findings indicated that MAO-A may be involved in pulmonary vascular remodeling and consecutive RV failure.
Topics: Animals; Clorgyline; Disease Models, Animal; Disease Progression; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Indoles; Monoamine Oxidase; Oxidative Stress; Pulmonary Arterial Hypertension; Pulmonary Artery; Pyrroles; Rats; Vascular Remodeling; Vascular Stiffness; Vasodilation
PubMed: 33264068
DOI: 10.1165/rcmb.2020-0105OC -
American Journal of Physiology. Heart... Jun 2023Right 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,...
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, = 29) or ambient normoxia (1,525 m/5,000 ft, = 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 ) hypertrophic gene expression and prosurvival mechanotransduction through YAP-TAZ signaling, ) extracellular matrix (ECM) remodeling, ) inflammatory cell activation, and ) 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. 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.
Topics: Animals; Cattle; Hypertension, Pulmonary; Endothelial Cells; Mechanotransduction, Cellular; Proteomics; Hypertrophy, Right Ventricular; Heart Ventricles; Heart Failure; Disease Models, Animal; Hypoxia; Ventricular Remodeling; Ventricular Function, Right; Ventricular Dysfunction, Right
PubMed: 36961489
DOI: 10.1152/ajpheart.00614.2022 -
Lipids in Health and Disease May 2020Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the...
BACKGROUND
Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children.
PATIENTS AND METHODS
In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex.
RESULTS
Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97).
CONCLUSION
Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.
Topics: Adolescent; Body Mass Index; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Dyslipidemias; Echocardiography; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Insulin; Lipids; Male; Obesity; Serbia; Triglycerides
PubMed: 32456629
DOI: 10.1186/s12944-020-01285-9 -
The Journal of Obstetrics and... Aug 2023To explore left ventricular structural/functional abnormalities in preeclampsia patients by using multimodal echocardiography and to analyze the cardiac impact in...
AIM
To explore left ventricular structural/functional abnormalities in preeclampsia patients by using multimodal echocardiography and to analyze the cardiac impact in preeclampsia subtypes.
METHODS
A total of 103 individuals, including 64 preeclampsia patients and 39 healthy pregnant women were recruited for this study from 2019 to 2021. There were 34 patients with preeclampsia with severe features (SPE) patients and 30 with preeclampsia with nonsevere features (NSPE), including 9 with early-onset NSPE (EO-NSPE) patients, 27 early-onset SPE (EO-SPE) patients, 21 later-onset NSPE (LO-NSPE), and 7 with later-onset SPE (LO-SPE). All patients underwent multimodal echocardiography before treatment, including two-dimensional, Doppler, and speckle-tracking echocardiography, to evaluate left ventricular structure/function. Analysis of variance was used to determine statistical significance across groups.
RESULTS
EO-SPE patients showed decreased left ventricular ejection fractions, peak longitudinal systolic strain at apical four-chambers, peak circumferential, and radial systolic strain at the apical and mitral annular plane systolic excursion (MAPSE), and increased mitral regurgitation compared to other preeclampsia patients. Compared to LO-NSPE and EO-SPE patients, LO-SPE patients showed increased left ventricular mass indexed to height and early diastolic left ventricular diastolic filling/mitral annular velocity, and decreased MAPSE and early/late diastolic mitral annular velocity.
CONCLUSION
EO-SPE patients were characterized by left ventricular injury and systolic function reduced. LO-SPE patients were characterized by left ventricular hypertrophy and reduced diastolic function. Multimodal echocardiography can detect myocardial injury in PE patients at an early stage.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Echocardiography; Ventricular Function, Left; Heart Ventricles; Stroke Volume
PubMed: 37259850
DOI: 10.1111/jog.15699 -
Experimental Animals Nov 2021Transverse aortic constriction (TAC) has been widely used to study cardiac hypertrophy, fibrosis, diastolic dysfunction, and heart failure in rodents. Few studies have...
Transverse aortic constriction (TAC) has been widely used to study cardiac hypertrophy, fibrosis, diastolic dysfunction, and heart failure in rodents. Few studies have been reported in preclinical animal models. The similar physiology and anatomy between non-human primates (NHPs) and humans make NHPs valuable models for disease modeling and testing of drugs and devices. In the current study, we aimed to establish a TAC model in NHPs and characterize the structural and functional profiles of the heart after TAC. A non-absorbable suture was placed around the aorta between the brachiocephalic artery and left common carotid artery to create TAC. NHPs were divided into 2 groups according to pressure gradient (PG): the Mild Group (PG=31.01 ± 12.40 mmHg, n=3) and the Moderate Group (PG=53.00 ± 9.37 mmHg, n=4). At 4 weeks after TAC, animals in both TAC groups developed cardiac hypertrophy: enlarged myocytes and increased wall thickness of the left ventricular (LV) anterior wall. Although both TAC groups had normal systolic function that was similar to a Sham Group, the Moderate Group showed diastolic dysfunction that was associated with more severe cardiac fibrosis, as evidenced by a reduced A wave velocity, large E wave velocity/A wave velocity ratio, and short isovolumic relaxation time corrected by heart rate. Furthermore, no LV arrhythmia was observed in either animal group after TAC. A diastolic dysfunction model with cardiac hypertrophy and fibrosis was successfully developed in NHPs.
Topics: Animals; Aorta, Thoracic; Constriction; Disease Models, Animal; Female; Heart; Heart Ventricles; Macaca fascicularis; Male; Ventricular Function, Left
PubMed: 34135271
DOI: 10.1538/expanim.21-0050 -
PloS One 2020We evaluated the effects of grape juice (Vitis labrusca L.) on dyslipidemia, resistance to insulin, and left ventricular hypertrophy (LVH) in mice homozygous for the...
OBJECTIVE
We evaluated the effects of grape juice (Vitis labrusca L.) on dyslipidemia, resistance to insulin, and left ventricular hypertrophy (LVH) in mice homozygous for the absence of the LDL receptor gene (LDLr -/-) under a hyperlipidemic diet.
METHODOLOGY
We divided 30 male mice (3 months old) into three groups (n = 10); the HL group was fed a high-fat diet, the HLU group received a high-fat diet and 2 g/kg/day of grape juice, and the HLS group was fed a high-fat diet and simvastatin (20 mg/kg/day). We assessed the blood pressure profile of the mice. We also determined the levels of C-reactive protein (CRP) and lipid profile, glycemic and insulinemic profiles, and calculated the HOMA-IR. Cardiomyocyte hypertrophy, interstitial collagen deposit, and the expression of CD40 ligand (CD40L) and metalloproteinases 2 and 9 were assessed immunohistologically.
RESULTS
After 60 days, the mice treated with grape juice showed similar results as those of the group treated with simvastatin. The use of grape fruit attenuated dyslipidemia and insulin resistance and significantly increased the levels of high cholesterol density lipoproteins (HDLc). The antioxidant potential of phenolic compounds associated with the increase in HDLc levels in the mice of the HLU group prevented the development of LVH and arterial hypertension since it inhibited the inflammatory response induced by the CD40 pathway and its ligand CD40L. Consequently, there was a lower expression of MMP-2 and MMP-9 and lower serum levels of CRP.
CONCLUSION
Grape juice has a hypolipidemic and cardiac protective potential, presenting a similar effect as that of simvastatin through a direct antioxidant action of phenolic compounds, or indirectly, via antioxidant action and anti-inflammatory activity of the HDLc. These results suggest that grape juice is a functional food possessing a high potential to prevent cardiovascular diseases.
Topics: Animals; Blood Pressure; C-Reactive Protein; CD40 Ligand; Collagen; Diet, High-Fat; Dyslipidemias; Fruit and Vegetable Juices; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Protective Agents; Receptors, LDL; Simvastatin; Vitis
PubMed: 32881885
DOI: 10.1371/journal.pone.0238163 -
Journal of Hypertension May 2021Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical...
OBJECTIVES
Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking.
METHODS
Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors.
RESULTS
In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P < 0.001; YFS: β=0.41, P < 0.001) and LVMI (BHS: β=0.14, P < 0.001; YFS: β=0.09, P < 0.001). In addition, we found that the relationship between FLI and LVMI was stronger in women than men (BHS: P-interaction = 0.01; YFS: P-interaction < 0.01); and the relationship between FLI and LVM/LVMI was stronger in black than white individuals (LVM: P-interaction = 0.02; LVMI: P-interaction = 0.04). Moreover, we found that the associations of FLI with LVM and LVMI were attenuated by high physical activity, especially in BHS (P-interaction = 0.02).
CONCLUSION
Our findings from two independent prospective cohorts indicate that FLI is positively associated with LVM/LVMI, independent of traditional cardiovascular risk factors. Such relationships are more pronounced among women and black individuals and are attenuated by high physical activity.
Topics: Cardiovascular Diseases; Echocardiography; Fatty Liver; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Prospective Studies; Risk Factors
PubMed: 33560053
DOI: 10.1097/HJH.0000000000002716