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Cardiovascular Research Feb 2020In patients with pulmonary hypertension, right ventricular hypertrophy (RVH) is a detrimental condition that ultimately results in right heart failure and death. The...
AIMS
In patients with pulmonary hypertension, right ventricular hypertrophy (RVH) is a detrimental condition that ultimately results in right heart failure and death. The ubiquitin proteasome system has been identified as a major protein degradation system to regulate cardiac remodelling in the left heart. Its role in right heart hypertrophy, however, is still ambiguous.
METHODS AND RESULTS
RVH was induced in mice by pulmonary artery banding (PAB). Both, expression and activity of the proteasome was found to be up-regulated in the hypertrophied right ventricle (RV) compared to healthy controls. Catalytic inhibition of the proteasome by the two proteasome inhibitors Bortezomib (BTZ) and ONX-0912 partially improved RVH both in preventive and therapeutic applications. Native gel analysis revealed that specifically the 26S proteasome complexes were activated in experimental RVH. Increased assembly of 26S proteasomes was accompanied by elevated expression of Rpn6, a rate-limiting subunit of 26S proteasome assembly, in hypertrophied cardiomyocytes of the right heart. Intriguingly, patients with RVH also showed increased expression of Rpn6 in hypertrophied cardiomyocytes of the RV as identified by immunohistochemical staining.
CONCLUSION
Our data demonstrate that alterations in expression and activity of proteasomal subunits play a critical role in the development of RVH. Moreover, this study provides an improved understanding on the selective activation of the 26S proteasome in RVH that might be driven by the rate-limiting subunit Rpn6. In RVH, Rpn6 therefore represents a more specific target to interfere with proteasome function than the commonly used catalytic proteasome inhibitors.
Topics: Animals; Disease Models, Animal; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Inflammation Mediators; Mice; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Signal Transduction; Ubiquitination; Ventricular Function, Right; Ventricular Remodeling
PubMed: 31020333
DOI: 10.1093/cvr/cvz103 -
Turkish Journal of Medical Sciences Oct 2021It is known that the presence of fragmented QRS (fQRS) on electrocardiography (ECG) is associated with cardiovascular events. The aim of this study was the evaluation of...
BACKGROUND/AIM
It is known that the presence of fragmented QRS (fQRS) on electrocardiography (ECG) is associated with cardiovascular events. The aim of this study was the evaluation of fQRS formation and its relationship with the left ventricular hypertrophy (LVH) parameters in acromegaly patients.
MATERIALS AND METHODS
In total, 47 previously diagnosed with non-hypertensive acromegaly patients and 48 control subjects were included in the study. ECG and transthoracic echocardiography (TTE) were performed for each participant. Acromegaly patients were divided into two groups according to the fQRS formation on the ECG. Left ventricular wall thicknesses, and left atrial diameter (LAD), left ventricular mass (LVM), left ventricular mass index (LVMi), and relative wall thickness (RWT) were obtained.
RESULTS
In control group 5 (10.4%) and in acromegaly group 17 (36.2%) patients had fQRS on ECG (p = 0.003). LAD [36.0 (34.0–38.0) vs. 38.0 (35.0–41.0) mm, p < 0.001], LVM [155.27 ± 27.00 vs. 173.0 (153.0–235.0) g, p < 0.001], LVMi [83.12 ± 13.19 vs. 92.0 (83.0–118.0) g/m², p < 0.001] and RWT [0.39 ± 0.03 vs. 0.43 (0.41–0.45), p = 0.001] were significantly higher in patients with acromegaly. Disease duration was significantly higher (11.59 ± 1.3 vs. 8.2 ± 1.8 years, p < 0.001) in the fQRS (+) group. LAD [41.0 (39.0–42.5) vs. 37.0 (34.7–38.0) mm, p < 0.001], LVM [219.0 (160.5–254.5) vs. 164.0 (153.0–188.0) g, p = 0.017], LVMi [117.0 (92.5–128.5) vs. 86.0 (82.0–100.2) g/m², p = 0.013] and RWT [0.44 (0.42–0.49) vs. 0.43 (0.40–0.44), p = 0.037] were significantly higher in fQSR (+) acromegaly patients. In multivariate logistic regression analysis, disease duration (odds ratio: 10.05, 95% CI: 1.099–92.012, p = 0.041) and LAD (odds ratio: 2.19, 95% CI: 1.030–4.660, p = 0.042) were found to be the independent predictors of fQRS formation.
CONCLUSION
The results of our study revealed that fQRS (+) acromegaly patients had increased LVH parameters compared to fQRS (-) patients.
Topics: Acromegaly; Adult; Aged; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged
PubMed: 33992041
DOI: 10.3906/sag-2101-229 -
Journal of Cardiovascular Translational... Feb 2021There is no consensus regarding the benefit of antihypertensive therapy on left ventricular structure and function. The most of studies investigated the effect of... (Review)
Review
There is no consensus regarding the benefit of antihypertensive therapy on left ventricular structure and function. The most of studies investigated the effect of therapy on left ventricular hypertrophy, less studies were focused on left ventricular diastolic dysfunction and the minority on left ventricular mechanics. The majority of investigations showed positive effect of antihypertensive therapy on regression of left ventricular remodeling. Nevertheless, it is very difficult to distinguish the effect of antihypertensive medication from the effect of blood pressure reduction on left ventricular improvement. The other important issue in these studies is difficulty to distinguish the effect of left ventricular hypertrophy regression from the effect of antihypertensive medications on left ventricular diastolic function and mechanics. The novel findings suggest that the cascade of left ventricular remodeling in hypertensive heart disease begins with mechanical changes, continuous with diastolic dysfunction, and ends with left ventricular hypertrophy. This is very important paradigm because it enables early and timely diagnosis of subclinical left ventricular damage in hypertensive patients and should provide rapid detection of left ventricular function improvement during antihypertensive therapy.
Topics: Antihypertensive Agents; Blood Pressure; Diastole; Echocardiography; Heart Ventricles; Humans; Hypertension; Myocardial Contraction; Ventricular Function, Left; Ventricular Remodeling
PubMed: 32086702
DOI: 10.1007/s12265-020-09970-x -
Relationship between Soluble ST2 and Left Ventricular Geometry in Maintenance Hemodialysis Patients.Blood Purification 2021Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance... (Clinical Trial)
Clinical Trial
INTRODUCTION
Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance hemodialysis (MHD) patients. Different left ventricular geometry may provide additional clinical information. Soluble ST2 is a novel cardiac prognostic biomarker in MHD patients and is closely related to cardiac remodeling.
OBJECTIVE
This study sought to evaluate the association of sST2 and left ventricular structure in a cohort of MHD patients.
METHODS
Two hundred eighty-seven patients were enrolled. Left ventricular structure was assessed via transthoracic echocardiography. Left ventricular geometric patterns were defined according to left ventricular mass index and relative wall thickness (RWT). Serum sST2 levels were measured.
RESULTS
Prevalence of LVH was 44.9% in the study population. In univariate analysis, sST2 levels were correlated with interventricular septal wall thickness, posterior wall thickness, and RWT. After multivariate adjustment, sST2 was independently correlated with only RWT (p = 0.028). Comparing sST2 concentrations across different LV geometric patterns, we found sST2 levels were significantly increased in patients with concentric cardiac remodeling and concentric LVH.
CONCLUSIONS
The present study found that sST2 were significantly increased in patients with concentric remodeling and concentric LVH. ST2/interleukin (IL)-33 signaling might participate in the process of cardiac remodeling via its pro-fibrotic action. Future studies on the mechanism of ST2/IL-33 pathway are needed.
Topics: Aged; Biomarkers; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Renal Dialysis; Ventricular Remodeling
PubMed: 33291107
DOI: 10.1159/000508402 -
The American Journal of Forensic... Dec 2023Hypertrophy of the heart is assessed by heart weight (and dimensions) and myocyte hypertrophy. Establishing an association between the two may be useful in assessing...
Hypertrophy of the heart is assessed by heart weight (and dimensions) and myocyte hypertrophy. Establishing an association between the two may be useful in assessing hypertrophy in cases where there are limitations in assessing the heart weight. This preliminary study explored the association between the number of binucleated myocytes (a feature of myocyte hypertrophy) in a randomly chosen single high-power field of the left ventricular free wall and heart weight in an adult White population. It also compared the number of binucleated myocytes between cases with increased heart weight (>400 g in female and >500 g in male) and cases with normal heart weight. Heart weight and number of binucleated myocytes correlated significantly in male only. Increased heart weight had a significantly higher number of binucleated myocytes, with 8.5 binucleated myocytes being able to segregate cases with increased heart weight (74% sensitivity and 79% specificity). The results of this study showed the number of binucleated myocytes may have a complementary role in assessing hypertrophy of the heart.
Topics: Adult; Male; Female; Humans; Myocardium; Heart; Cardiomegaly; Heart Ventricles; Hypertrophy; Muscle Cells; Myocytes, Cardiac
PubMed: 37527350
DOI: 10.1097/PAF.0000000000000869 -
Circulation. Cardiovascular Imaging Jun 2021Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic...
BACKGROUND
Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic resonance (CMR)-derived LV mass may improve LVH detection.
METHODS
Within 32 239 individuals of the UK Biobank prospective cohort who underwent CMR and 12-lead ECG, we trained a convolutional neural network to predict CMR-derived LV mass using 12-lead ECGs (left ventricular mass-artificial intelligence [LVM-AI]). In independent test sets (UK Biobank [n=4903] and Mass General Brigham [MGB, n=1371]), we assessed correlation between LVM-AI predicted and CMR-derived LV mass and compared LVH discrimination using LVM-AI versus traditional ECG-based rules (ie, Sokolow-Lyon, Cornell, lead aVL rule, or any ECG rule). In the UK Biobank and an ambulatory MGB cohort (MGB outcomes, n=28 612), we assessed associations between LVM-AI predicted LVH and incident cardiovascular outcomes using age- and sex-adjusted Cox regression.
RESULTS
LVM-AI predicted LV mass correlated with CMR-derived LV mass in both test sets, although correlation was greater in the UK Biobank (r=0.79) versus MGB (r=0.60, P<0.001 for both). When compared with any ECG rule, LVM-AI demonstrated similar LVH discrimination in the UK Biobank (LVM-AI c-statistic 0.653 [95% CI, 0.608 -0.698] versus any ECG rule c-statistic 0.618 [95% CI, 0.574 -0.663], P=0.11) and superior discrimination in MGB (0.621; 95% CI, 0.592 -0.649 versus 0.588; 95% CI, 0.564 -0.611, P=0.02). LVM-AI-predicted LVH was associated with incident atrial fibrillation, myocardial infarction, heart failure, and ventricular arrhythmias.
CONCLUSIONS
Deep learning-inferred LV mass estimates from 12-lead ECGs correlate with CMR-derived LV mass, associate with incident cardiovascular disease, and may improve LVH discrimination compared to traditional ECG rules.
Topics: Artificial Intelligence; Deep Learning; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Prospective Studies
PubMed: 34126762
DOI: 10.1161/CIRCIMAGING.120.012281 -
Echocardiography (Mount Kisco, N.Y.) Apr 2022Pregnancy is a process that can cause several physiologic changes to the cardiovascular system such as ventricular hypertrophy and dilation of cardiac chambers. Although...
INTRODUCTION
Pregnancy is a process that can cause several physiologic changes to the cardiovascular system such as ventricular hypertrophy and dilation of cardiac chambers. Although there are studies about pregnancy-related changes in echocardiographic examination; there is no data about the long-term effects of parity on these alterations. Therefore, we evaluated the long-term effect of pregnancy on right ventricular (RV) dilation and RV hypertrophy and their relation to the parity number.
METHODS
This prospective study included a total of 600 women (200 consecutive women who had no parity, 200 women who had a parity number of 1 to 4 and 200 women who had a parity number of more than 4). Right chambers' measurements were compared between the groups.
RESULTS
In echocardiographic analysis, RV and right atrial dimensions and areas and RV wall thickness were higher in parous women. On the other hand, RV systolic function parameters were significantly lower in parous women. These significant changes showed a gradual increase or decrease by increasing parity number. By multivariate hierarchical logistic regression analysis, the four independent factors that increased the risk of RV dilation were age (OR: 1.16 CI: 1.10-1.20), body mass index (OR: 1.05, CI: 1.02-1.08), smoking (OR: 1.87, CI: 1.28-4.02), and giving a birth (OR: 3.94 CI: 1.82-8.81). There was also independent relationship between the number of parity and RV hypertrophy even after adjustment for several confounders.
CONCLUSION
Pregnancy-related physiological changes mostly resolve after delivery. This study about long-term effects of pregnancy on RV has demonstrated that there is a significant relation between the number of parity and either RV dilation or RV hypertrophy. Each parity had also additive effect on these changes.
Topics: Female; Heart; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Parity; Pregnancy; Prospective Studies; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 35253268
DOI: 10.1111/echo.15333 -
Turk Kardiyoloji Dernegi Arsivi : Turk... Apr 2023Down syndrome is a genetic syndrome characterized with various dysmorphisms and congenital malformations such as congenital heart diseases. We aimed to evaluate the...
OBJECTIVE
Down syndrome is a genetic syndrome characterized with various dysmorphisms and congenital malformations such as congenital heart diseases. We aimed to evaluate the relationship between Down syndrome, hypothyroidism, and cardiac ���ndings.
METHODS
Thyroid hormone pro���les and echocardiographic ���ndings were evaluated. Patients with hypothyroidism and Down syndrome were named group 1; patients with hypothyroidism without Down syndrome group 2 and group 3 was control. The echocardiographic parameters (interventricular septum and left ventricular systolic, diastolic posterior wall thickness, left ventricular end-diastolic diameter, ejection fraction) were indexed to body surface area. Left ventricular mass index and relative wall thickness were calculated. Patients with relative wall thickness equal to or below 0.42 were classi���ed as eccentric hypertrophy or normal geometry, while those over 0.42 as concentric remodeling or concentric hypertrophy.
RESULTS
Thyroid stimulating hormone values of groups 1 and 2 were signi���cantly higher than those of group 3. There were no signi���cant di���erences for fT4 between the groups. Interventricular septum and left ventricular posterior wall end-diastolic and end-systolic thickness were signi���cantly higher in group 1 than groups 2 and 3. There was no statistically signi���cant di���erence in left ventricular mass index between groups 1 and 2. In terms of relative wall thickness, 16 out of 29 patients in group 1 were revealed as concentric remodeling, 12 as normal geometry, 1 patient as eccentric hypertrophy. In group 2, 6 patients were revealed as concentric remodeling, 14 as normal geometry. There was no statistically signi���cant di���erence of left ventricular end-diastolic thickness between 3 groups.
CONCLUSION
Cardiac morphology and functions were signi���cantly a���ected by hypothyroidism in patients with Down syndrome. Hypertrophy in Down syndrome may be caused by the cellular changes in myocardium.
Topics: Humans; Child; Down Syndrome; Heart; Echocardiography; Heart Ventricles; Hypertrophy; Hypothyroidism; Hypertrophy, Left Ventricular; Hypertension
PubMed: 36999332
DOI: 10.5543/tkda.2023.70337 -
Computers in Biology and Medicine May 2023In our paper, we simulated cardiac hypertrophy with the use of shell elements in parametric and echocardiography-based left ventricle (LV) models. The hypertrophy has an...
In our paper, we simulated cardiac hypertrophy with the use of shell elements in parametric and echocardiography-based left ventricle (LV) models. The hypertrophy has an impact on the change in the wall thickness, displacement field and the overall functioning of the heart. We computed both eccentric and concentric hypertrophy effects and tracked changes in the ventricle shape and wall thickness. Thickening of the wall was developed under the influence of concentric hypertrophy, while the eccentric hypertrophy produces wall thinning. To model passive stresses we used the recently developed material modal based on the Holzapfel experiments. Also, our specific shell composite finite element models for heart mechanics are much smaller and simpler to use with respect to conventional 3D models. Furthermore, the presented modeling approach of the echocardiography-based LV can serve as the basis for practical applications since it relies on the true patient-specific geometry and experimental constitutive relationships. Our model gives an insight into hypertrophy development in realistic heart geometries, and it has the potential to test medical hypotheses regarding hypertrophy evolution in a healthy and heart with a disease, under the influence of different conditions and parameters.
Topics: Humans; Heart Ventricles; Hypertrophy, Left Ventricular; Echocardiography; Cardiomegaly; Heart; Hypertension
PubMed: 36933415
DOI: 10.1016/j.compbiomed.2023.106742 -
Cells Dec 2021Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved...
Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.
Topics: Animals; Cell Proliferation; Heart Ventricles; Humans; Hypoxia; Indoles; Isoquinolines; Lung; Male; Metabolome; Myosin Light Chains; Phosphorylation; Proto-Oncogene Proteins c-akt; Pulmonary Arterial Hypertension; Pyrroles; Rats, Sprague-Dawley; Sulfonamides; TOR Serine-Threonine Kinases; Vascular Remodeling; Rats
PubMed: 35011628
DOI: 10.3390/cells11010066