696 results on '"HCM"'
Search Results
52. Prognostic value of global longitudinal strain in hypertrophic cardiomyopathy: A systematic review and meta‐analysis.
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Yang, Ying, Wu, Dong, Wang, Hui, and Wang, Yanting
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HYPERTROPHIC cardiomyopathy ,PROGNOSIS ,MAJOR adverse cardiovascular events - Abstract
Background: As previously reported, impairment of left ventricular global longitudinal strain (LVGLS) is associated with myocardial fibrosis, arrhythmias, and heart failure in hypertrophic cardiomyopathy (HCM) patients. Hypothesis: This study aimed to estimate the association between LVGLS measured by echocardiography and major adverse cardiovascular events (MACE) in patients with HCM. Methods: Pubmed, Embase, Scopus, and Cochrane Library databases were systematically searched for evaluating the difference of LVGLS between MACE and non‐MACE and the relevance of LVGLS and MACE in HCM patients, mean difference (MD), and pooled hazard ratios (HR) with 95% confidence interval (CI) were calculated. Publication bias was detected by funnel plots and Egger's test, and trim‐and‐fill analysis was employed when publication bias existed. Results: A total of 13 studies reporting 2441 HCM patients were included in this meta‐analysis. Absolute value of LVGLS was lower in the group of HCM with MACE (MD = 2.74, 95% CI: 2.50–2.99, p <.001; I2 = 0, p =.48). In the pooled unadjusted model, LVGLS was related to MACE (HR = 1.14, 95% CI: 1.06–1.22, p <.05, I2 = 58.4%, p <.01) and there is a mild heterogeneity, and sensitivity analysis showed stable results. In the pooled adjusted model, LVGLS was related to MACE (HR = 1.12, 95% CI: 1.08–1.16, p <.05; I2 = 0%, p =.442). Egger's tests showed publication bias, and trim‐and‐fill analysis was applied, with final results similar to the previous and still statistically significant. Conclusion: The meta‐analysis suggested that impaired LVGLS was associated with poor prognosis in HCM patients. [ABSTRACT FROM AUTHOR]
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- 2022
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53. Function Generation Synthesis of the Four-bar Linkage Based on Four and Five Precision Points using Newton-HCM.
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Varedi-Koulaei, Seyed Mojtaba
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NEWTON-Raphson method ,NUMERICAL functions ,CONTINUATION methods - Abstract
The length values selection for a determined type of linkage to achieve the necessary task, dimensional synthesis, is classified into three classes based on the mechanism’s task: function generation, path generation, and motion generation. The case considered in this study, Function generation synthesis, aims to create a relation between the angular motions of the input and output links of the mechanism. For this problem, a semi-analytical method called the Newton-HCM is used for numerical solutions, which combines Newton’s method with the semi-analytical Homotopy Continuation Method (HCM). Function generation synthesis of a planar four-bar linkage for four and five precision points is the main challenge of the current study, which is highly nonlinear and complicated to solve. Numerical examples of the function generation problem for a four-bar linkage with four and five precision points are presented and authenticate the excellent performance of the proposed algorithm. [ABSTRACT FROM AUTHOR]
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- 2022
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54. Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs
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Karsten E. Schober, Phillip R. Fox, Jonathan Abbott, Etienne Côté, Virginia Luis‐Fuentes, Jose Novo Matos, Joshua A. Stern, Lance Visser, Katherine F. Scollan, Valerie Chetboul, Donald Schrope, Tony Glaus, Roberto Santilli, Romain Pariaut, Rebecca Stepien, Vanessa Arqued‐Soubeyran, Marco Baron Toaldo, Amara Estrada, Kristin MacDonald, Emily T. Karlin, and John Rush
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canine ,dynamic outflow tract obstruction ,HCM ,LV hypertrophy ,veterinary ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. Hypothesis/Objectives To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. Animals Sixty‐eight client‐owned dogs. Methods Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. Results Three hundred and forty‐five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly
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- 2022
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55. Unveiling MiRNA-124 as a biomarker in hypertrophic cardiomyopathy: An innovative approach using machine learning and intelligent data analysis.
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Pisklova, Maria and Osmak, German
- Abstract
Hypertrophic cardiomyopathy (HCM) is a widespread hereditary cardiac pathology characterized by thickened heart walls and rearrangement of cardiomyocytes. Despite extensive research, the mechanisms underlying HCM development remain poorly understood, impeding the development of effective therapeutic and diagnostic strategies. Recent studies have suggested a polygenic nature of HCM development alongside monogenic forms. Transcriptomic profiling is a valuable tool for investigating such diseases. In this study, we propose a novel approach to study regulatory microRNAs (miRNAs) in the context of HCM, utilizing state-of-the-art data analysis tools. Our method involves applying the Monte Carlo simulation and machine learning algorithm to transcriptomic data to generate high-capacity classifiers for HCM. From these classifiers, we extract key genes crucial for their performance, resulting in the identification of 16 key genes. Subsequently, we narrow down the pool of miRNAs by selecting those that may target the greatest number of key genes within the best models. We particularly focused on miR-124-3p, which we validated to have an association with HCM on an independent dataset. Subsequent investigation of its function revealed involvement of miR-124-3p in the RhoA signaling pathway. In this study we propose a new approach to analyze transcriptomic data to search for microRNAs associated with a disease. Using this approach for transcriptomic profiling data of patients with HCM, we identified miR-124-3p as a potential regulator of the RhoA signaling pathway in the pathogenesis of HCM. [Display omitted] • Hypertrophic cardiomyopathy (HCM) is supposed to have monogenic and polygenic nature • We propose a novel machine learning-based approach for analyzing transcriptomic data • New algorithm focuses on miR-124-3p and validates its association with HCM • MiR-124-3p is involved in HCM through RhoA signaling pathway [ABSTRACT FROM AUTHOR]
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- 2024
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56. Development of ventricular cell models for the study of alternans, heart failure and energetic impairment
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Jones, Gareth and Lu, Jian
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616.1 ,Ion Channels ,HCM ,Biophysics ,Computational Modelling ,Cardiac disease ,Cardiac modelling - Abstract
In this thesis the changes observed in human ventricular cells with disease are examined. As heart disease remains one of the leading causes of death in Europe computational modelling provides a powerful tool in understanding the mechanisms underlying changes observed with disease. In this project, an integrated model of a human ventricular cardiomyocyte incorporating electrophysiology, mitochondrial energetics and contraction was constructed. This model was then modified with recent data from patients with hypertrophic cardiomyopathy to allow insight into factors leading to exercise intolerance with the disease. The cell was found to be energetically impaired due to a combination of Ca2+ overload and mitochondrial dysfunction. The effect of three drugs were then tested on the model, each found to block Na+ and Ca2+ handling channels within the cell. Two of these drugs, K201 and SEA-0400 were found to improve the energetic status of the cell during exercise through a reduction in myofilament ATP consumption. Changes observed in mRNA expression were then utilised to modify a model of a previous human ventricular cell and update the regulation of RyR gating. Regulation by calsequestrin of the recovery from inactivation of the RyRs is found to mediate the production of alternans. Finally a compartmentalised model of spatial Ca2+ dynamics was updated with a recent model of mitochondrial energetics. Disruption of mitochondrial Ca2+ uptake is simulated and shown to result in mitochondrial dysfunction. Energetic impairment of localised processes within the cell due to dysfunction was investigated.
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- 2018
57. AS and HCM
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Madadi, Shabnam, Maleki, Majid, editor, and Alizadehasl, Azin, editor
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- 2021
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58. Competitive Sports Participation for Athletes With Genetic Heart Disease: A Whole New Ballgame.
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Kim, Jonathan H.
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SPORTS participation , *GENETIC disorders , *HEART diseases , *ATHLETES , *SUDDEN death - Abstract
[Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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59. Extended septal myectomy using a combined trans-aortic and apical approach for long basal and mid-cavity hypertrophic cardiomyopathy.
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Poddar, Aayush, Murugesan, Karthik Babu, and Padmanabhan, Chandrasekar
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Surgical septal myectomy is the treatment of choice for patients of hypertrophic cardiomyopathy who are symptomatic despite maximal medical therapy. Residual obstruction results in the persistence of symptoms and poorer outcomes. The length (depth) of the septum excised as far towards the apex is important. A combined approach of trans-aortic and trans-apical is needed to achieve this in specific cases with associated mid-cavity obstruction. We present a case of a complex long-segment septal hypertrophy which underwent a successful septal reduction using a combined trans-aortic and trans-apical approach. [ABSTRACT FROM AUTHOR]
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- 2022
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60. Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction.
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Chen, Hao, Tesic, Milorad, Nikolic, Valentina N., Pavlovic, Milan, Vucic, Rada M., Spasic, Ana, Jovanovic, Hristina, Jovanovic, Ivana, Town, Stephanie E. L., Padula, Matthew P., and McClements, Lana
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VENTRICULAR ejection fraction , *HEART failure , *HYPERTROPHIC cardiomyopathy , *BIOMARKERS , *PHENOTYPES , *LIQUID chromatography-mass spectrometry , *TIME-of-flight mass spectrometry - Abstract
Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM. [ABSTRACT FROM AUTHOR]
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- 2022
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61. Epigenetic Study of Cohort of Monozygotic Twins With Hypertrophic Cardiomyopathy Due to MYBPC3 (Cardiac Myosin-Binding Protein C).
- Author
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Peñarroya A, Lorca R, Rodríguez Reguero JJ, Gómez J, Avanzas P, Tejedor JR, Fernandez AF, and Fraga MF
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- Humans, Male, Female, Middle Aged, Cardiomyopathy, Hypertrophic genetics, Adult, Phenotype, Hypertrophy, Left Ventricular genetics, Hypertrophy, Left Ventricular physiopathology, Diseases in Twins genetics, Diseases in Twins blood, Genetic Predisposition to Disease, Severity of Illness Index, Twins, Monozygotic genetics, DNA Methylation, Epigenesis, Genetic, Carrier Proteins genetics
- Abstract
Background: Hypertrophic cardiomyopathy is an autosomal dominant cardiac disease. The mechanisms that determine its variable expressivity are poorly understood. Epigenetics could play a crucial role in bridging the gap between genotype and phenotype by orchestrating the interplay between the environment and the genome regulation. In this study we aimed to establish a possible correlation between the peripheral blood DNA methylation patterns and left ventricular hypertrophy severity in patients with hypertrophic cardiomyopathy, evaluating the potential impact of lifestyle variables and providing a biological context to the observed changes., Methods and Results: Methylation data were obtained from peripheral blood samples (Infinium MethylationEPIC BeadChip arrays). We employed multiple pair-matched models to extract genomic positions whose methylation correlates with the degree of left ventricular hypertrophy in 3 monozygotic twin pairs carrying the same founder pathogenic variant ( MYBPC3 p.Gly263Ter). This model enables the isolation of the environmental influence, beyond age, on DNA methylation changes by removing the genetic background. Our results revealed a more anxious personality among more severely affected individuals. We identified 56 differentially methylated positions that exhibited moderate, proportional changes in methylation associated with left ventricular hypertrophy. These differentially methylated positions were enriched in regions regulated by repressor histone marks and tended to cluster at genes involved in left ventricular hypertrophy development, such as HOXA5 , TRPC3 , UCN3 , or PLSCR2 , suggesting that changes in peripheral blood may reflect myocardial alterations., Conclusions: We present a unique pair-matched model, based on 3 monozygotic twin pairs carrying the same founder pathogenic variant and different phenotypes. This study provides further evidence of the pivotal role of epigenetics in hypertrophic cardiomyopathy variable expressivity.
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- 2024
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62. Detection of Left Atrial Remodeling by Three-Dimensional Echocardiography in Symptomatic Patients Known to Had Non-Obstructive Hypertrophic Cardiomyopathy.
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Abd Elkareem TS, Habib S, Shehata A, and Elhady F
- Abstract
Background: Hypertrophic cardiomyopathy (HCM) is one of the most prevalent inherited disorders and a common cause of sudden heart death. Left atrial (LA) dilatation frequently occurs in patients with HCM as a result of impaired left ventricular (LV) relaxation or associated involvement of LA myocardium in HCM., Methods: We enrolled 170 patients known to had HCM (non-obstructive type) and 30 healthy subjects (control group). All of them underwent two-dimensional (2D) echocardiography to measure LV dimensions, function, LA dimension, LA deformations, pulmonary artery pressure (PAP) and LV global longitudinal strain (LVGLS). LA volumes and mechanics were also measured by three-dimensional (3D) echocardiography., Results: By 2D echocardiography, patient group revealed significantly lower all LA functions vs. control group including reservoir (26 ± 4 vs. 43 ± 3, P < 0.001), conduit (-14 ± 2 vs. -25 ± 2, P < 0.001), and booster pump functions (-12 ± 2 vs. -18 ± 1, P < 0.001). PAP was significantly higher in patient group (42 ± 7 vs. 27 ± 4 in control group). LVGLS was significantly lower in patient group (-15±1.4% vs. -23±2% in control group). Using 3D speckle tracking echocardiography (STE), there were a significantly higher indexed maximum LA volume (Vmax indexed) (43.5 ± 5.6 vs. 28.7 ± 3.7, P < 0.001), but significantly lower left atrial strain at reservoir function (LASr) (24 ± 4 vs. 41 ± 3, P < 0.001), left atrial strain at conduit function (LAScd) (-13 ± 2 vs. -24 ± 2, P < 0.001), and left atrial strain at contractile function (LASct) (-11 ± 2 vs. -18 ± 1, P < 0.001)., Conclusion: Three-dimensional transthoracic echocardiography (TTE) is a feasible method for the assessment of LA remodeling, but there is adverse LA remodeling in patients with long-standing non-obstructive HCM including impaired all LA mechanics and with increased septal thickness, there are more diastolic dysfunction and more reduction of LA mechanics., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2024, Abd Elkareem et al.)
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- 2024
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63. Association Between Parathyroid Hormone-Related Peptide Levels and Mortality in Patients With Malignancy.
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Kimura A, Kato K, Nakashima A, Maruyama Y, Ohkido I, Miyazaki Y, and Yokoo T
- Abstract
Objective: Hypercalcemia of malignancy is a risk factor for mortality in patients with malignancies. Although the parathyroid hormone-related protein (PTHrP) secreted by tumor cells induces hypercalcemia, the association between serum PTHrP levels and mortality remains unclear. This study aimed to investigate the association between serum PTHrP levels and mortality in patients with malignancies., Methods: We included patients with hypercalcemia (>10 mg/dL) and elevated PTHrP levels (>1.1 pmol/L) and analyzed mortality (overall survival after cancer diagnosis, PTHrP measurement, and 5-year survival rate). Moreover, using Cox proportional hazard model analysis, we investigated the impact of PTHrP levels on survival prognosis, assessing whether this effect varied depending on calcium concentration., Results: We analyzed the data of 183 patients. The median PTHrP level, corrected calcium level, and age were 5.5 (3.0-10.6) pmol/L, 12.5 (11.5-13.4) mg/dl, and 70 (61-76) years, respectively. PTHrP was significantly and linearly associated with serum calcium levels (correlation coefficient, 0.06; 95% CI: 0.039-0.081, t: 5.69; P < .001). The group with the highest PTHrP levels had significantly worse survival rates than the group with the lowest PTHrP levels (hazard ratio: 1.68, 95% CI 1.03-2.77, P = .038)., Conclusion: This study showed an association between PTHrP and mortality in patients with malignancy after adjusting for serum calcium levels., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)
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- 2024
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64. Comparison of Drug Therapy Efficacy in Patients With Hypertrophic Cardiomyopathy: A Network Meta-Analysis.
- Author
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Shang E and Tan H
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- Humans, Stroke Volume, Oxygen Consumption drug effects, Tetrazoles therapeutic use, Benzimidazoles therapeutic use, Cardiovascular Agents therapeutic use, Randomized Controlled Trials as Topic, Losartan therapeutic use, Valsartan therapeutic use, Treatment Outcome, Cardiomyopathy, Hypertrophic drug therapy, Network Meta-Analysis, Biphenyl Compounds therapeutic use
- Abstract
The aim of this network meta-analysis was to compare the efficacy of various commonly used drugs in treating patients with hypertrophic cardiomyopathy (HCM). Randomized controlled trials on drugs for HCM treatment were retrieved from PubMed, Embase, Cochrane Library, and Web of Science (search cutoff: January 10, 2024). Quality assessment was performed using the risk of bias tool, and data analysis used R software. Seventeen studies (1,133 patients with HCM) were included. The network meta-analysis indicated that mavacamten and perhexiline improved peak oxygen consumption compared with placebo. Mavacamten reduced N-terminal pro-B-type natriuretic peptide, left ventricular mass index, left atrial volume index, and septal E/e' ratio. Losartan decreased systolic blood pressure, whereas candesartan, mavacamten, and valsartan reduced maximum wall thickness. Perhexiline had better efficacy in increasing peak oxygen consumption, and candesartan in reducing maximum wall thickness. No drug significantly improved left ventricular ejection fraction compared with placebo. In conclusion, on the basis of current studies, commonly used drugs may effectively improve some of the outcome measures in patients with HCM, whereas the novel drug mavacamten showed significant therapeutic effects in most of the remaining outcome measures except for left ventricular ejection fraction., Competing Interests: Declaration of competing interest Dr. Tan reports financial support, study publishing charges, statistical analysis, and writing assistance were provided by Sun Yat-Sen University. The remaining author has no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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65. A New Model to Evaluate Percent-Time-Spent-Following on Two-Lane Highways
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Vivek, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Mathew, Tom V., editor, Joshi, Gaurang J., editor, Velaga, Nagendra R., editor, and Arkatkar, Shriniwas, editor
- Published
- 2020
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66. Using HCM Method in Estimation the Highway Capacity and Recommendation Traffic Management for a Section of National Highway #5 - VietNam
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Hieu, Tran Trung, Lam, Trinh Xuan, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Ha-Minh, Cuong, editor, Dao, Dong Van, editor, Benboudjema, Farid, editor, Derrible, Sybil, editor, Huynh, Dat Vu Khoa, editor, and Tang, Anh Minh, editor
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- 2020
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67. Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model.
- Author
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Da'as, Sahar Isa, Hasan, Waseem, Salem, Rola, Younes, Nadine, Abdelrahman, Doua, Mohamed, Iman A., Aldaalis, Arwa, Temanni, Ramzi, Mathew, Lisa Sara, Lorenz, Stephan, Yacoub, Magdi, Nomikos, Michail, Nasrallah, Gheyath K., and Fakhro, Khalid A.
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- *
HYPERTROPHIC cardiomyopathy , *CARRIER proteins , *BRACHYDANIO , *TRANSCRIPTOMES , *PROTEIN C , *MYOSIN , *ACTIN - Abstract
Variants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart's contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant's total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model. [ABSTRACT FROM AUTHOR]
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- 2022
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68. Regulation of SMAD Signaling Pathway by miRNAs Associated with Myocardial Fibrosis: In silico Analysis of Target Gene Networks.
- Author
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Pisklova, Maria, Osmak, German, and Favorova, Olga
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- *
GENE regulatory networks , *CELLULAR signal transduction , *MICRORNA , *SMAD proteins , *NON-coding RNA - Abstract
Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease caused by mutations in the sarcomere genes, which is accompanied by myocardial fibrosis leading to progressive heart failure and arrhythmias. Recent studies suggest that the HCM development involves dysregulation of gene expression. Among the molecules involved in this process are microRNAs (miRNAs), which are short non-coding RNAs. Typically, one miRNA regulates several target genes post-transcriptionally, hence, it might be difficult to determine the role of a particular miRNA in the disease pathogenesis. In this study, using the PubMed database, we selected 15 miRNAs whose expression is associated with myocardial fibrosis, one of the critical pathological processes in HCM. We then used an earlier developed algorithm to search in silico for the signaling pathways regulated by these miRNAs and found that ten of them participate in the regulation of the TGF-β/SMAD signaling pathway. At the same time, among the SMAD signaling pathway genes, the target of the most identified miRNAs was the MYC gene, which is involved in the development of fibrosis in some tissues. In our earlier work, we found that the TGF-β/SMAD pathway is also regulated by a set of other miRNAs associated with the myocardial hypertrophy in HCM. The fact that two sets of miRNAs identified in two independent bioinformatic studies are involved in the regulation of the same signaling pathway indicates that the SMAD signaling cascade is indeed a key element in the regulation of pathological processes in HCM. The obtained data might contribute to understanding pathological processes underlying HCM development. [ABSTRACT FROM AUTHOR]
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- 2022
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69. Characterization of cardiac metabolism in iPSC-derived cardiomyocytes: lessons from maturation and disease modeling.
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Vučković, Sofija, Dinani, Rafeeh, Nollet, Edgar E., Kuster, Diederik W. D., Buikema, Jan Willem, Houtkooper, Riekelt H., Nabben, Miranda, van der Velden, Jolanda, and Goversen, Birgit
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- *
HEART metabolism , *HYPERTROPHIC cardiomyopathy , *DISEASE progression , *GENOME editing , *PLURIPOTENT stem cells , *ENERGY consumption - Abstract
Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a powerful tool for disease modeling, though their immature nature currently limits translation into clinical practice. Maturation strategies increasingly pay attention to cardiac metabolism because of its pivotal role in cardiomyocyte development and function. Moreover, aberrances in cardiac metabolism are central to the pathogenesis of cardiac disease. Thus, proper modeling of human cardiac disease warrants careful characterization of the metabolic properties of iPSC-CMs. Methods: Here, we examined the effect of maturation protocols on healthy iPSC-CMs applied in 23 studies and compared fold changes in functional metabolic characteristics to assess the level of maturation. In addition, pathological metabolic remodeling was assessed in 13 iPSC-CM studies that focus on hypertrophic cardiomyopathy (HCM), which is characterized by abnormalities in metabolism. Results: Matured iPSC-CMs were characterized by mitochondrial maturation, increased oxidative capacity and enhanced fatty acid use for energy production. HCM iPSC-CMs presented varying degrees of metabolic remodeling ranging from compensatory to energy depletion stages, likely due to the different types of mutations and clinical phenotypes modeled. HCM further displayed early onset hypertrophy, independent of the type of mutation or disease stage. Conclusions: Maturation strategies improve the metabolic characteristics of iPSC-CMs, but not to the level of the adult heart. Therefore, a combination of maturation strategies might prove to be more effective. Due to early onset hypertrophy, HCM iPSC-CMs may be less suitable to detect early disease modifiers in HCM and might prove more useful to examine the effects of gene editing and new drugs in advanced disease stages. With this review, we provide an overview of the assays used for characterization of cardiac metabolism in iPSC-CMs and advise on which metabolic assays to include in future maturation and disease modeling studies. [ABSTRACT FROM AUTHOR]
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- 2022
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70. Identification of Underlying Hub Genes Associated with Hypertrophic Cardiomyopathy by Integrated Bioinformatics Analysis
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Ma Z, Wang X, Lv Q, Gong Y, Xia M, Zhuang L, Lu X, Yang Y, Zhang W, Fu G, Ye Y, and Lai D
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hypertrophic cardiomyopathy ,hcm ,weighted gene coexpression network analysis ,wgcna ,hub gene ,biomarkers ,bioinformatics analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Zetao Ma,1,2,* Xizhi Wang,1,* Qingbo Lv,1 Yingchao Gong,1 Minghong Xia,1 Lenan Zhuang,1 Xue Lu,1 Ying Yang,1 Wenbin Zhang,1 Guosheng Fu,1 Yang Ye,1 Dongwu Lai1 1Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310016, People’s Republic of China; 2Department of Cardiology, Zhongshan People’s Hospital, Zhongshan, Guangdong Province, 528403, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongwu Lai; Yang YeKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang Province, 310016, People’s Republic of ChinaTel +86-571-86006241Fax +86-571-86006246Email laidw@zju.edu.cn; yeyang1222@zju.edu.cnBackground: Considered as one of the major reasons of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease. However, effective treatment for HCM is still lacking. Identification of hub gene may be a powerful tool for discovering potential therapeutic targets and candidate biomarkers.Methods: We analysed three gene expression datasets for HCM from the Gene Expression Omnibus. Two of them were merged by “sva” package. The merged dataset was used for analysis while the other dataset was used for validation. Following this, a weighted gene coexpression network analysis (WGCNA) was performed, and the key module most related to HCM was identified. Based on the intramodular connectivity, we identified the potential hub genes. Then, a receiver operating characteristic curve analysis was performed to verify the diagnostic values of hub genes. Finally, we validated changes of hub genes, for genetic transcription and protein expression levels, in datasets of HCM patients and myocardium of transverse aortic constriction (TAC) mice.Results: In the merged dataset, a total of 455 differentially expressed genes (DEGs) were identified from normal and hypertrophic myocardium. In WGCNA, the blue module was identified as the key module and the genes in this module showed a high positive correlation with HCM. Functional enrichment analysis of DEGs and key module revealed that the extracellular matrix, fibrosis, and neurohormone pathways played important roles in HCM. FRZB, COL14A1, CRISPLD1, LUM, and sFRP4 were identified as hub genes in the key module. These genes showed a good predictive value for HCM and were significantly up-regulated in HCM patients and TAC mice. We also found protein expression of LUM and sFRP4 increased in myocardium of TAC mice.Conclusion: This study revealed that five hub genes are involved in the occurrence and development of HCM, and they are potentially to be used as therapeutic targets and biomarkers for HCM.Keywords: hypertrophic cardiomyopathy, HCM, weighted gene coexpression network analysis, WGCNA, hub gene, biomarkers, bioinformatics analysis
- Published
- 2021
71. Sepsis-induced suicidal left ventricular in a patient with hypertrophic cardiomyopathy/hypertrophic obstructive cardiomyopathy
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K Roshan Rao, Sarita Rao, and Ankur Gupta
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hcm ,hocm ,lvot ,Medicine - Abstract
Hypertrophic cardiomyopathy is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy. In this case, a 48-year-male patient presented with complaints of shortness of breath, uneasiness for 15 days, right lower limb pain, and one episode of fever for 2 days. He was initiated on antibiotics but gradually started developing hypotension and oliguria. After optimizing the medical therapy and as a life-saving measure, alcoholic septal ablation was done in this patient as a last resort. The patient was weaned off the ventilator after 72 h and discharged in a stable condition. He has continued follow-up for 8 months and is asymptomatic; the gradient has not recurred. The patient had both issues, and timely alcohol septal ablation helped save the patient by optimizing the hemodynamics. This is a rare situation of suicidal left ventricular induced by sepsis-induced vasodilation.
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- 2022
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72. Automated three‐dimensional echocardiographic quantification for left ventricular volume and function in patients with hypertrophic cardiomyopathy.
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Wang, Yushan, Zhang, Li, Liu, Jia, Yue, Xiaofei, Shi, Heshui, Li, Yuman, Xie, Mingxing, and Lv, Qing
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ECHOCARDIOGRAPHY , *LEFT heart ventricle , *CONFIDENCE intervals , *ACADEMIC medical centers , *CARDIAC hypertrophy , *MAGNETIC resonance imaging , *PEARSON correlation (Statistics) , *WORKFLOW , *INTER-observer reliability , *T-test (Statistics) , *AUTOMATION , *DESCRIPTIVE statistics , *HEART physiology , *ODDS ratio - Abstract
Background: Accurate, reproducible, noninvasive determination of left ventricular (LV) volumes and ejection fraction (EF) is important for clinical assessment, selection of therapy, and serial monitoring of patients with hypertrophic cardiomyopathy (HCM). Current clinical Two‐dimensional echocardiography (2DE) may cause inaccurate measurements in patients with HCM because of their asymmetric ventricles and limitations of 2DE technology. Three‐dimensional echocardiography (3DE) have demonstrated significantly greater accuracy. However, the time‐consuming workflow limits the clinical utility of 3DE. Aim: We aim to compare the performance of a novel automated 3DE system (HeartModel, Philips Healthcare) with 2DE in a group of patients with HCM. Cardiac magnetic resonance (CMR) was reference standard. Methods: Fifty‐three patients with HCM were examined by automated 3DE (3DEA), two‐dimensional biplane Simpson's method (2DBP), manual 3DE method, and CMR, respectively. For patients with poor automated quantification, manual correction was performed. The Pearson correlation coefficient and Bland‐Altman analysis and paired Student t tests were used to assess inter‐technique agreement. Results: 3DEA measurements with contour editing correlate well with CMR and manual 2DE and 3DE measurements (r =.80–.96). The analysis time of 3DEA was shorter than that of 2DBP (3DEA, 141 ± 15s; 2DBP, 174 ± 17 s). Inter‐observer variability was reduced significantly with use of 3DEA. Conclusion: Compared with current clinical 2DBP method, the analysis time of automated 3DE was much shorter with the added benefit of enhanced accuracy and reproducibility. Patients with asymmetric chamber may rely more on the timesaving automated 3DE quantification in the future. [ABSTRACT FROM AUTHOR]
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- 2022
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73. Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs.
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Schober, Karsten E., Fox, Phillip R., Abbott, Jonathan, Côté, Etienne, Luis‐Fuentes, Virginia, Matos, Jose Novo, Stern, Joshua A., Visser, Lance, Scollan, Katherine F., Chetboul, Valerie, Schrope, Donald, Glaus, Tony, Santilli, Roberto, Pariaut, Romain, Stepien, Rebecca, Arqued‐Soubeyran, Vanessa, Toaldo, Marco Baron, Estrada, Amara, MacDonald, Kristin, and Karlin, Emily T.
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- *
HYPERTROPHIC cardiomyopathy , *LEFT heart ventricle , *DOGS , *DOG breeds , *CONGESTIVE heart failure , *MITRAL valve , *HEART murmurs , *SUDDEN death - Abstract
Background: There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. Hypothesis/Objectives: To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. Animals: Sixty‐eight client‐owned dogs. Methods: Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. Results: Three hundred and forty‐five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly <10 kg (85%), and without a sex predilection. Twenty‐four % were Shih Tzu and 24% terrier breeds. Most (80%) had a systolic heart murmur. Owner‐determined exercise intolerance (37%) and syncope (18%) were most commonly reported signs. The majority (84%) of dogs had symmetrical LV hypertrophy, whereas asymmetrical septal and LV free wall hypertrophy was observed in 9% and 6% of dogs, respectively. Isolated basal interventricular septal hypertrophy was not observed. Commonly recorded were systolic anterior motion of the mitral valve (60%) and LV diastolic dysfunction (89% of dogs where diastolic function was evaluated). Six dogs died unexpectedly, and 3 developed congestive heart failure. Known survival times were between 1 day and 114 months after diagnosis. Conclusions and Clinical Importance: Hypertrophic cardiomyopathy in dogs should be considered as a differential diagnosis if LV hypertrophy is identified. Small breed dogs are overrepresented, and it is uncommon for dogs with HCM to develop CHF although sudden death can occur. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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74. Whole mitochondrial genome sequencing of Malaysian patients with cardiomyopathy.
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Sheh Wen Kuan, Kek Heng Chua, E-Wei Tan, Lay Koon Tan, Alexander Loch, and Boon Pin Kee
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WHOLE genome sequencing ,EXOMES ,CARDIOMYOPATHIES ,MITOCHONDRIAL DNA ,MALAYSIANS ,ASIANS - Abstract
Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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75. Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy
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Maureen S. Oldach, Yu Ueda, Eric S. Ontiveros, Samantha L. Fousse, Lance C. Visser, and Joshua A. Stern
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Feline ,Pharmacodynamics ,HCM ,Obstruction ,Inotrope ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. Results Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. Conclusions In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.
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- 2021
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76. Pedestrian walking speed at un-signalized midblock crosswalk and its impact on urban street segment performance
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Albert Forde and Janice Daniel
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Midblock ,Pedestrian ,Walking speed ,HCM ,Urban ,Street ,Transportation engineering ,TA1001-1280 - Abstract
The Urban Street Segment Chapter of the Highway Capacity Manual (HCM) includes a methodology for evaluating the level of service urban street segments provide to automobile users. The methodology does not account for pedestrian activity at un-signalized midblock crosswalk on an urban street segment. Pedestrian activity at un-signalized midblock crosswalk on urban street segments causes friction conditions between automobiles and pedestrians. As a consequence, the average time it takes vehicles to travel along the segment is increased. Increasing segment running time decreases both the travel speed of automobiles and the level of service provided to automobile users. There is an inverse relationship between the delay incurred by interrupted vehicles and the speeds at which pedestrians walk while crossing at midblock. To account for this delay, there is a need to investigate pedestrian walking speeds at un-signalized midblock crosswalks. This study measured pedestrian walking speeds by age-group at two un-signalized midblock crosswalks on urban street segments. The first objective of this paper is to perform statistical analyses to examine the measured free-flow pedestrian walking speeds. The second objective is to demonstrate how the findings of this study can be incorporated into the Urban Street Segment Analysis Chapter of the HCM. Pedestrian walking speeds were recorded and analyzed for 2937 pedestrians. The results show teenagers walk at an average speed of 1.45 m/s, young adults walk at an average speed of 1.55 m/s, middle age pedestrians walk at a speed of 1.45 m/s, older pedestrians walk at speed of 1.09 m/s, and elderly or physically disabled pedestrians walk at a speed of 1.04 m/s.
- Published
- 2021
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77. Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy
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Lazar Velicki, Djordje G. Jakovljevic, Andrej Preveden, Miodrag Golubovic, Marija Bjelobrk, Aleksandra Ilic, Snezana Stojsic, Fausto Barlocco, Maria Tafelmeier, Nduka Okwose, Milorad Tesic, Paul Brennan, Dejana Popovic, Arsen Ristic, Guy A. MacGowan, Nenad Filipovic, Lars S. Maier, and Iacopo Olivotto
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Hypertrophic cardiomyopathy ,HCM ,Hereditary cardiac disease ,Left ventricular hypertrophy ,MYBPC3 ,MYH7 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Methods As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e′ ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). Conclusions Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
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- 2020
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78. Contrast-free detection of myocardial fibrosis in hypertrophic cardiomyopathy patients with diffusion-weighted cardiovascular magnetic resonance.
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Nguyen, Christopher, Lu, Minjie, Fan, Zhaoyang, Bi, Xiaoming, Kellman, Peter, Zhao, Shihua, and Li, Debiao
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Myocardium ,Humans ,Cardiomyopathy ,Hypertrophic ,Fibrosis ,Contrast Media ,Image Interpretation ,Computer-Assisted ,Diffusion Magnetic Resonance Imaging ,Prognosis ,Severity of Illness Index ,Predictive Value of Tests ,Adult ,Middle Aged ,Female ,Male ,Young Adult ,Hypertrophic cardiomyopathy ,HCM ,Diffusion-weighting ,Cardiovascular magnetic resonance ,Extracellular volume mapping ,ECV ,Cardiomyopathy ,Hypertrophic ,Image Interpretation ,Computer-Assisted ,Cardiorespiratory Medicine and Haematology ,Nuclear Medicine & Medical Imaging - Abstract
BackgroundsPrevious studies have shown that diffusion-weighted cardiovascular magnetic resonance (DW-CMR) is highly sensitive to replacement fibrosis of chronic myocardial infarction. Despite this sensitivity to myocardial infarction, DW-CMR has not been established as a method to detect diffuse myocardial fibrosis. We propose the application of a recently developed DW-CMR technique to detect diffuse myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients and compare its performance with established CMR techniques.MethodsHCM patients (N = 23) were recruited and scanned with the following protocol: standard morphological localizers, DW-CMR, extracellular volume (ECV) CMR, and late gadolinium enhanced (LGE) imaging for reference. Apparent diffusion coefficient (ADC) and ECV maps were segmented into 6 American Heart Association (AHA) segments. Positive regions for myocardial fibrosis were defined as: ADC > 2.0 μm(2)/ms and ECV > 30%. Fibrotic and non-fibrotic mean ADC and ECV values were compared as well as ADC-derived and ECV-derived fibrosis burden. In addition, fibrosis regional detection was compared between ADC and ECV calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) using ECV as the gold-standard reference.ResultsADC (2.4 ± 0.2 μm(2)/ms) of fibrotic regions (ADC > 2.0 μm(2)/ms) was significantly (p 30%) was significantly (p
- Published
- 2015
79. Hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) diagnosis using echocardiography and electrocardiography.
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Forghani, Yasna, Behnam, Hamid, and Shojaeifard, Maryam
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ECHOCARDIOGRAPHY ,ELECTROCARDIOGRAPHY ,CARDIOVASCULAR diseases ,CARDIOLOGISTS ,LEFT ventricular hypertrophy ,HYPERTROPHIC cardiomyopathy - Abstract
Echocardiography and electrocardiogram (ECG) are the primary tools used by cardiologists to diagnose cardiovascular heart diseases. Contrary to the critical role of combining the echocardiography and ECG information in clinical examinations, to our knowledge, no study has considered this to classify heart diseases. Left ventricular hypertrophy (LVH) is caused by a variety of origins such as hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD). Differentiating HCM and HHD is challenging. We proposed an HCM and HHD patient classifier to use ECG and echocardiography information. Longitudinal strain and strain rate from echocardiography frames and amplitude and temporal features from ECG signals, are extracted. To eliminate incompetent features, Fisher's discrimination ratio (FDR), information gain, and Relief-F weights are used. Finally, support vector machine (SVM) and K-nearest neighbours classifiers are used to classify the normal, HCM, and HHD subjects. The results on 30 subjects show that the best classification refers to SVM classifier using five selected features from ECG and echocardiography information using FDR. The precision, sensitivity, and F-measure are 97.62, 93.33 and 95.43%, respectively. According to the results, the combination of echocardiography and ECG information leads to diagnosis improvement compared to the classification based on separated information of ECG and echocardiography. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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80. FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility
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Michael Chhor, Hao Chen, Djurdja Jerotić, Milorad Tešić, Valentina N. Nikolić, Milan Pavlović, Rada M. Vučić, Benjamin Rayner, Chris J. Watson, Mark Ledwidge, Kenneth McDonald, Tracy Robson, Kristine C. McGrath, and Lana McClements
- Subjects
heart failure ,biomarkers ,heart failure with preserved ejection fraction ,HFpEF ,HCM ,hypertrophic cardiomyopathy ,Microbiology ,QR1-502 - Abstract
Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated—for the first time—FKBPL’s role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01–0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.
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- 2023
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81. Genetic Basis of Hypertrophic Cardiomyopathy in Cats.
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Grzeczka A, Graczyk S, Pasławski R, and Pasławska U
- Abstract
Hypertrophic cardiomyopathy (HCM) is a common cardiovascular condition in cats, affecting yth males and females of all ages. Some breeds, such as Ragdolls and Maine Coons, can develop HCM at a young age. The disease has a wide range of progression and severity, characterized by various pathological changes in the heart, including arteritis, fibrous tissue deposition, and myocardial cell hypertrophy. Left ventricular hypertrophy, which can restrict blood flow, is a common feature of HCM. The disease may persist into old age and eventually lead to heart failure and increased diastolic pressure. The basis of HCM in cats is thought to be genetic, although the exact mechanisms are not fully understood. Mutations in sarcomeric proteins, in particular myosin-binding protein C (MYBPC3), have been identified in cats with HCM. Two specific mutations, MYBPC3 [R818W] and MYBPC3 [A31P], have been classified as 'pathogenic'. Other variants in genes such as MYBPC3, TNNT2, ALMS1, and MYH7 are also associated with HCM. However, there are cases where cats without known genetic mutations still develop HCM, suggesting the presence of unknown genetic factors contributing to the disease. This work aims to summarise the new knowledge of HCM in cats and the alterations in cardiac tissue as a result of genetic variants.
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- 2024
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82. Discontinuation of afterload-reducing drugs decreases left ventricular outflow tract obstruction in hypertrophic obstructive cardiomyopathy.
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Derda AA, Abelmann M, Sonnenschein K, Sieweke JT, Bavendiek U, Bauersachs J, Thum T, and Berliner D
- Abstract
Background: Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is classified into hypertrophic non-obstructive and hypertrophic obstructive cardiomyopathy (HOCM). Patients with HOCM and coexisting heart failure or arterial hypertension are often prescribed afterload-reducing drugs. Although recommended in current guidelines, data on the direct effect of discontinuing afterload-reducing medication are scarce. This study aims to demonstrate the benefit of discontinuing afterload-reducing medication in HOCM patients., Methods: This monocentric retrospective analysis included 24 patients with HOCM with afterload-reducing medication, including angiotensin-converting enzyme inhibitors, angiotensin-1 receptor blocker and dihydropyridine-calcium channel blocker, at their first outpatient visit. Effects of discontinuing this medication on LVOTO were examined compared to patients with persistent use despite medical advice., Results: 16 patients discontinued their afterload-reducing drugs, resulting in a significant decrease in median LVOT gradient from 86.5 [60.5-109.3] mmHg to 61.5 [28.3-97.50] mmHg ( p = 0.0004). In 6 patients, beta-blocker therapy was initiated simultaneously, or the dose was increased. Regardless, LVOT gradient reduction was also significant in the remaining 10 patients ( p = 0.001). The gradient was not changed significantly in the 8 patients continuing their afterload-reducing medication., Conclusions: Discontinuation of afterload-reducing drugs significantly decreases LVOTO. Our study underscores the significance of abstaining from afterload-reducing drugs in HOCM patients, particularly in patients with concomitant hypertension or heart failure. According to recently published European guidelines, HOCM patients should preferably be treated with beta-blockers or non-dihydropyridine-calcium channel blockers., Competing Interests: AD received honoraria for lectures by AstraZeneca, BMS, Boehringer Ingelheim and Bayer not related to this article. KS received presentation honoraria and travel grants from medi, Novartis, BMS, Chiesi and Amicus. JB received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, Roche not related to this article; and research support for the department from Zoll, CVRx, Abiomed, Norgine, Roche, not related to this article. DB received honoraria for lectures/consulting from Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Derda, Abelmann, Sonnenschein, Sieweke, Bavendiek, Bauersachs, Thum and Berliner.)
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- 2024
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83. Atrial Fibrillation Substrate and Catheter Ablation Outcomes in MYBPC3- and MYH7-Mediated Hypertrophic Cardiomyopathy.
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Haq IU, Akhiyat N, Al-Shakarchi N, Siontis KC, Mulpuru SK, Sugrue A, Giudicessi J, Friedman PA, Asirvatham SJ, and Killu AM
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- Humans, Middle Aged, Female, Male, Retrospective Studies, Aged, Adult, Treatment Outcome, Atrial Fibrillation surgery, Atrial Fibrillation genetics, Atrial Fibrillation physiopathology, Catheter Ablation methods, Carrier Proteins genetics, Cardiomyopathy, Hypertrophic genetics, Cardiomyopathy, Hypertrophic surgery, Cardiomyopathy, Hypertrophic physiopathology, Myosin Heavy Chains genetics, Cardiac Myosins genetics
- Abstract
Background: The effects of disease-causing MYBPC3 or MYH7 genetic variants on atrial myopathy, atrial fibrillation (AF) clinical course, and catheter ablation efficacy remain unclear., Objectives: The aim of this study was to characterize the atrial substrate of patients with MYBPC3- or MYH7-mediated hypertrophic cardiomyopathy (HCM) and its impact on catheter ablation outcomes., Methods: A retrospective single-center study of patients with HCM who underwent genetic testing and catheter ablation for AF was performed. Patients with MYBPC3- or MYH7-mediated HCM formed the gene-positive cohort; those without disease-causative genetic variants formed the control cohort. High-density electroanatomical mapping was performed using a 3-dimensional mapping system, followed by radiofrequency ablation., Results: Twelve patients were included in the gene-positive cohort (mean age 55.6 ± 9.9 years, 83% men, 50% MYBPC3, 50% MYH7, mean ejection fraction 59.3% ± 13.7%, mean left atrial [LA] volume index 51.7 ± 13.1 mL/m
2 , mean LA pressure 20.2 ± 5.4 mm Hg) and 15 patients in the control arm (mean age 61.5 ± 12.6 years, 60% men, mean ejection fraction 64.9% ± 5.1%, mean LA volume index 54.1 ± 12.8 mL/m2 , mean LA pressure 19.6 ± 5.41 mm Hg). Electroanatomical mapping demonstrated normal voltage in 87.7% ± 5.03% of the LA in the gene-positive cohort and 94.3% ± 3.58% of the LA in the control cohort (P < 0.001). Of the abnormal regions, intermediate scar (0.1-0.5 mV) accounted for 6.33% ± 1.97% in the gene-positive cohort and 3.07% ± 2.46% in the control cohort (P < 0.01). Dense scar (<0.1 mV) accounted for 5.93% ± 3.20% in the gene-positive cohort and 2.61% ± 2.19% in the control cohort (P < 0.01). Freedom from AF at 12 months was similar between the gene-positive (75%) and control (73%) cohorts (P = 0.92), though a greater number of procedures were required in the gene-positive cohort., Conclusions: Patients with MYBPC3- or MYH7-mediated HCM undergoing AF ablation have appreciably more low-amplitude LA signals, suggestive of fibrosis. However, catheter ablation remains an effective rhythm-control strategy., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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84. A cost-effectiveness analysis of hypertrophic cardiomyopathy sudden cardiac death risk algorithms for implantable cardioverter defibrillator decision-making.
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Green N, Chen Y, O'Mahony C, Elliott PM, Barriales-Villa R, Monserrat L, Anastasakis A, Biagini E, Gimeno JR, Limongelli G, Pavlou M, and Omar RZ
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- Female, Humans, Male, Middle Aged, Algorithms, Cost-Effectiveness Analysis, Markov Chains, Primary Prevention economics, Primary Prevention methods, Quality of Life, Quality-Adjusted Life Years, Risk Assessment methods, United Kingdom epidemiology, Cardiomyopathy, Hypertrophic therapy, Cardiomyopathy, Hypertrophic complications, Cardiomyopathy, Hypertrophic economics, Death, Sudden, Cardiac prevention & control, Death, Sudden, Cardiac epidemiology, Defibrillators, Implantable economics
- Abstract
Aims: To conduct a contemporary cost-effectiveness analysis examining the use of implantable cardioverter defibrillators (ICDs) for primary prevention in patients with hypertrophic cardiomyopathy (HCM)., Methods: A discrete-time Markov model was used to determine the cost-effectiveness of different ICD decision-making rules for implantation. Several scenarios were investigated, including the reference scenario of implantation rates according to observed real-world practice. A 12-year time horizon with an annual cycle length was used. Transition probabilities used in the model were obtained using Bayesian analysis. The study has been reported according to the Consolidated Health Economic Evaluation Reporting Standards checklist., Results: Using a 5-year SCD risk threshold of 6% was cheaper than current practice and has marginally better total quality adjusted life years (QALYs). This is the most cost-effective of the options considered, with an incremental cost-effectiveness ratio of £834 per QALY. Sensitivity analyses highlighted that this decision is largely driven by what health-related quality of life (HRQL) is attributed to ICD patients and time horizon., Conclusion: We present a timely new perspective on HCM-ICD cost-effectiveness, using methods reflecting real-world practice. While we have shown that a 6% 5-year SCD risk cut-off provides the best cohort stratification to aid ICD decision-making, this will also be influenced by the particular values of costs and HRQL for subgroups or at a local level. The process of explicitly demonstrating the main factors, which drive conclusions from such an analysis will help to inform shared decision-making in this complex area for all stakeholders concerned., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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85. Olfactory schwannoma with hypertrophic cardiomyopathy: incidental association?
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Mondal, Sudipta, Sivadasanpillai, Harikrishnan, and Poyuran, Rajalakshmi
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HYPERTROPHIC cardiomyopathy ,SMELL disorders ,OLFACTORY nerve ,HYPERTENSIVE crisis ,HYPERTROPHY ,HISTOPATHOLOGY - Abstract
This article discusses a case of a 60-year-old woman who presented with hypertensive emergency and was found to have an olfactory schwannoma and hypertrophic cardiomyopathy (HCM). The patient underwent surgery to remove the schwannoma and was found to have no residual lesion post-surgery. Histopathology confirmed the diagnosis of schwannoma, and cardiac evaluation revealed asymmetrical septal hypertrophy and LVOT obstruction, confirming the diagnosis of HCM. The association between HCM and olfactory nerve schwannoma has not been previously reported, and further research is needed to understand the genetic implications of this association. [Extracted from the article]
- Published
- 2023
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86. The modified US heart allocation system improves transplant rates and decreases status upgrade utilization for patients with hypertrophic cardiomyopathy.
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Fowler, Cody C., Helmers, Mark R., Smood, Benjamin, Iyengar, Amit, Patrick, William, Alan Herbst, D., Altshuler, Peter, Han, Jason J., Kelly, John, and Atluri, Pavan
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- *
HYPERTROPHIC cardiomyopathy , *HEART transplant recipients , *TRANSPLANTATION of organs, tissues, etc. , *ADULTS , *TREATMENT effectiveness - Abstract
On October 18, 2018, the US heart allocation policy was restructured to improve transplant waitlist outcomes. Previously, hypertrophic cardiomyopathy (HCM) patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system. Retrospective analysis was performed of the United Network for Organ Sharing Transplant Database for all isolated adult single-organ first-time heart transplant patients with HCM listed between October 17, 2013 and September 4, 2020. Patients were divided by listing date into eras based on allocation system. Era 1 spanned October 17, 2013 to October 17th, 2018 and Era 2 spanned October 18th, 2018 to September 4, 2020. During the study period, 436 and 212 HCM patients were listed in Eras 1 and 2, respectively. Across eras, no differences in gender, ethnicity, BMI or functional status were noted (p >0.05). LVAD utilization remained low (Era 1: 3.7% vs Era 2: 3.3%, p = 0.297). Status upgrades decreased from 49.1% to 31.6% across eras (p = 0.001). There was no statistically significant difference in waitlist mortality across eras (p = 0.332). Transplant rates were improved in Era 2 (p = 0.005). Waitlist time among transplanted patients decreased in Era 2 from 97.1 to 63.9 days (p <0.001). There was no difference in one-year survival post-transplant (p = 0.602). The new allocation system has significantly increased transplant rates, shortened waitlist times, and decreased status upgrade utilization for HCM patients. Moreover, waitlist mortality remained unchanged in the new system. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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87. Low-intensity late gadolinium enhancement predominates in hypertrophic cardiomyopathy.
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Naeger, David M, Higgins, Charles, De Marco, Teresa, Muzzarelli, Stefano, and Ordovas, Karen G
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Myocardium ,Humans ,Cardiomyopathy ,Hypertrophic ,Gadolinium ,Contrast Media ,Imaging ,Three-Dimensional ,Magnetic Resonance Imaging ,Image Enhancement ,Risk Factors ,Image Processing ,Computer-Assisted ,Adolescent ,Adult ,Aged ,Middle Aged ,Female ,Male ,Young Adult ,DCE ,HCM ,Hypertrophic cardiomyopathy ,LGE ,Late gadolinium enhancement ,Heart Disease ,Cardiovascular ,Heart Disease - Coronary Heart Disease ,Clinical Sciences ,Nuclear Medicine & Medical Imaging - Abstract
AimAssess the extent of low- versus high-intensity late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM).MethodsLow- versus high-intensity LGE indexed volumes in 19 HCM patients were compared to 23 myocardial infarction (MI) patients.ResultsTotal, low-, and high-intensity LGE volumes in HCM vs. MI were 7.6ml/m(2), 4.7, and 2.4 vs. 11.2, 2.5, and 7.1, respectively. Total LGE volume did not differ (P=.13), though low- and high-intensity did (P=.05, .004). 67% versus 26% of all LGE was low-intensity in HCM versus MI (P
- Published
- 2015
88. Progress of Genetics in Inherited Cardiomyopathies-Induced Heart Failure
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Zhang, Baoli, Yang, Xue, Feng, Ning, Jiang, Hong, Wang, Xiangdong, Series Editor, Jiang, Hong, editor, and Liu, Ming, editor
- Published
- 2018
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89. Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction
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Hao Chen, Milorad Tesic, Valentina N. Nikolic, Milan Pavlovic, Rada M. Vucic, Ana Spasic, Hristina Jovanovic, Ivana Jovanovic, Stephanie E. L. Town, Matthew P. Padula, and Lana McClements
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heart failure ,biomarkers ,heart failure with preserved ejection fraction ,HFpEF ,HCM ,hypertrophic cardiomyopathy ,Microbiology ,QR1-502 - Abstract
Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.
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- 2022
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90. Avaliação do efeito de faixas adicionais de subida em segmentos de rodovias de pista simples
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Frederico Amaral e Silva, José Elievam Bessa Júnior, Anáiram Lima Costa, André Luiz Cunha, Aline Ferreira Andalício, Diego Milli da Costa Velho, and Veridianne Soares Nazareth
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Nível de Serviço ,HCM ,Simulação de Tráfego ,Transportation engineering ,TA1001-1280 - Abstract
O novo método do Highway Capacity Manual (HCM) para calcular a capacidade e o nível de serviço de rodovias de pista simples deverá ser, provavelmente, baseado na Densidade de Veículos em Pelotões (FD). No Brasil, há poucos estudos que determinam o impacto de faixas adicionais em rodovias de pista simples, sobretudo envolvendo FD, que é o objetivo geral deste trabalho. Para isso, foi obtido um conjunto de dados de tráfego em segmentos de rodovia para calibrar e validar o simulador de tráfego VISSIM. Com uma versão recalibrada do simulador, foram gerados dados de tráfego em segmentos viários hipotéticos com e sem faixas adicionais, com os quais foram ajustados modelos de tráfego fluxo x FD. Os resultados da análise dos modelos indicaram que a proposta deste trabalho produziu valores de nível de serviço e de FD mais aderentes aos valores que foram observados em campo.
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- 2021
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91. Cardiac MRI findings to differentiate athlete's heart from hypertrophic (HCM), arrhythmogenic right ventricular (ARVC) and dilated (DCM) cardiomyopathy.
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Kübler, J., Burgstahler, C., Brendel, J. M., Gassenmaier, S., Hagen, F., Klingel, K., Olthof, S.-C., Blume, K., Wolfarth, B., Mueller, K. A. L., Greulich, S., and Krumm, P.
- Abstract
To provide clinically relevant criteria for differentiation between the athlete's heart and similar appearing hypertrophic (HCM), dilated (DCM), and arrhythmogenic right-ventricular cardiomyopathy (ARVC) in MRI. 40 top-level athletes were prospectively examined with cardiac MR (CMR) in two university centres and compared to retrospectively recruited patients diagnosed with HCM (n = 14), ARVC (n = 18), and DCM (n = 48). Analysed MR imaging parameters in the whole study cohort included morphology, functional parameters and late gadolinium enhancement (LGE). Mean left-ventricular enddiastolic volume index (LVEDVI) was high in athletes (105 ml/m
2 ) but significantly lower compared to DCM (132 ml/m2 ; p = 0.001). Mean LV ejection fraction (EF) was 61% in athletes, below normal in 7 (18%) athletes vs. EF 29% in DCM, below normal in 46 (96%) patients (p < 0.0001). Mean RV-EF was 54% in athletes vs. 60% in HCM, 46% in ARVC, and 41% in DCM (p < 0.0001). Mean interventricular myocardial thickness was 10 mm in athletes vs. 12 mm in HCM (p = 0.0005), 9 mm in ARVC, and 9 mm in DCM. LGE was present in 1 (5%) athlete, 8 (57%) HCM, 10 (56%) ARVC, and 21 (44%) DCM patients (p < 0.0001). Healthy athletes' hearts are characterized by both hypertrophy and dilation, low EF of both ventricles at rest, and increased interventricular septal thickness with a low prevalence of LGE. Differentiation of athlete's heart from other non-ischemic cardiomyopathies in MRI can be challenging due to a significant overlap of characteristics also seen in HCM, ARVC, and DCM. [ABSTRACT FROM AUTHOR]- Published
- 2021
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92. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy.
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Zampieri, Mattia, Argirò, Alessia, Marchi, Alberto, Berteotti, Martina, Targetti, Mattia, Fornaro, Alessandra, Tomberli, Alessia, Stefàno, Pierluigi, Marchionni, Niccolò, and Olivotto, Iacopo
- Abstract
Purpose of review: Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as β-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. These agents that offer a variable degree of symptomatic relief, often suboptimal, are often limited by side-effects and fail to address the key molecular abnormalities of the disease. Recent findings: Mavacamten is a novel, first-in-class, allosteric inhibitor of cardiac myosin ATPase, which reduces actin-myosin cross-bridge formation, thereby reducing myocardial contractility and improving myocardial energetic consumption in experimental HCM models. Following a successful Phase 2 study, the recently published phase III, placebo-controlled, randomized EXPLORER-HCM trial demonstrated the efficacy and safety of mavacamten in reducing left ventricular outflow tract obstruction and ameliorating exercise capacity, New York Heart Association functional class and health status in patients with obstructive HCM. Summary: Mavacamten represents the first agent specifically developed for HCM successfully tested in a Phase III trial, to be registered soon for clinical use, representing a radical change of paradigm in the pharmacological treatment of HCM. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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93. Sepsis-Induced Suicidal Left Ventricular in a Patient with Hypertrophic Cardiomyopathy/Hypertrophic Obstructive Cardiomyopathy.
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Rao, K. Roshan, Rao, Sarita, and Gupta, Ankur
- Abstract
Hypertrophic cardiomyopathy is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy. In this case, a 48-year-male patient presented with complaints of shortness of breath, uneasiness for 15 days, right lower limb pain, and one episode of fever for 2 days. He was initiated on antibiotics but gradually started developing hypotension and oliguria. After optimizing the medical therapy and as a life-saving measure, alcoholic septal ablation was done in this patient as a last resort. The patient was weaned off the ventilator after 72 h and discharged in a stable condition. He has continued follow-up for 8 months and is asymptomatic; the gradient has not recurred. The patient had both issues, and timely alcohol septal ablation helped save the patient by optimizing the hemodynamics. This is a rare situation of suicidal left ventricular induced by sepsis-induced vasodilation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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94. Calibrating HCM model for roundabout entry capacity under heterogeneous traffic
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Abdullah Ahmad and Rajat Rastogi
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Roundabout ,Entry capacity ,HCM ,Heterogeneous traffic ,Gap acceptance ,Hydraulic engineering ,TC1-978 ,Transportation engineering ,TA1001-1280 - Abstract
Abstract Roundabout is a channelized intersection where traffic moves around a central island, clockwise for left-side driving and anti-clockwise for right-side driving. Efficiently designed roundabouts can handle traffic very smoothly without causing any delay. The capacity of roundabouts used to be calculated by the weaving theory in India. However, calculation of the entry capacity in the recent literature is based on critical gaps and follow-up times, and the Highway Capacity Manual of US (HCM 2010) provides an equation to estimate the entry capacity of a roundabout by using the flow in passenger car unit per hour (PCU/h), critical gaps and follow-up times at the entry section. In order to examine whether the HCM equation applies to Indian traffic condition or not, we collected data from five roundabouts in India in this study. Relevant data were extracted/estimated to calibrate parameters of the HCM equation. The PCU for a vehicle was estimated on the basis of lagging headway and width of the vehicle, and the critical gap value for a vehicle was estimated by minimizing the sum of absolute difference in a gap with respect to the highest rejected and accepted gaps. Results show that the critical gap values obtained under heterogeneous traffic conditions are much lower than those given in the literature for homogeneous traffic conditions. In addition, the modified HCM equation based on the critical gap values was verified using the field data taken during the formation of a continuous and stable queue at the entry of a roundabout. It was found that a multiplicative adjustment factor needs to be calculated for different sizes of roundabouts to ensure the adjusted HCM equation represents well the traffic condition prevailing in developing countries like India. A test conducted at another roundabout validated that the entry capacity estimated from the calibrated and adjusted HCM model was consistent with the field entry capacity, and the calibrated and adjusted HCM model could predict the entry capacity of an approach to a roundabout quite accurately.
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- 2019
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95. Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model
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Sahar Isa Da’as, Waseem Hasan, Rola Salem, Nadine Younes, Doua Abdelrahman, Iman A. Mohamed, Arwa Aldaalis, Ramzi Temanni, Lisa Sara Mathew, Stephan Lorenz, Magdi Yacoub, Michail Nomikos, Gheyath K. Nasrallah, and Khalid A. Fakhro
- Subjects
hypertrophic cardiomyopathy ,HCM ,c-MYBPC3 ,actin ,RNA seq ,zebrafish knockout ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Variants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart’s contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant’s total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model.
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- 2022
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96. Managing the Learning Capacity of Organizational Culture in Relation to Organizational Commitment: Methodological and Empirical Overview
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Nakov Leonid and Ivanovski Igor
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organizational culture ,octapace model ,organizational commitment ,hcm ,Management. Industrial management ,HD28-70 - Abstract
The primary objective of the paper is to offer qualitative analysis based on the previous relevant theoretical and empirical work for the correlation between systematic and methodological implementation of organizational commitment throughout its learning capacity and organizational culture. The co-integration of the two critical issues stresses the significance and influence of contemporary and holistic models, such as, the OCTA-PACE model, and its convergence to High Commitment management Model (HCM), as highly important for organizational growth and competitiveness of business entities.
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- 2018
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97. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations.
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Pei, J., Schuldt, M., Nagyova, E., Gu, Z., el Bouhaddani, S., Yiangou, L., Jansen, M., Calis, J. J. A., Dorsch, L. M., Blok, C. Snijders, van den Dungen, N. A. M., Lansu, N., Boukens, B. J., Efimov, I. R., Michels, M., Verhaar, M. C., de Weger, R., Vink, A., van Steenbeek, F. G., and Baas, A. F.
- Subjects
- *
HYPERTROPHIC cardiomyopathy , *PATHOLOGICAL physiology , *MYOCARDIUM , *GENES , *HEART diseases - Abstract
Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts. Results: Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations. Conclusions: By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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98. High ECG Risk-Scores Predict Late Gadolinium Enhancement on Magnetic Resonance Imaging in HCM in the Young.
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Österberg, Anna Wålinder, Östman-Smith, Ingegerd, Jablonowski, Robert, Carlsson, Marcus, Green, Henrik, Gunnarsson, Cecilia, Liuba, Petru, and Fernlund, Eva
- Subjects
- *
MAGNETIC resonance imaging , *BRUGADA syndrome , *ELECTROCARDIOGRAPHY , *GADOLINIUM , *HYPERTROPHIC cardiomyopathy , *HEART fibrosis - Abstract
An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). Myocardial fibrosis measured by cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) also affects prognosis. We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis or perfusion deficit on CMR in HCM. In total 42 individuals (7–31 years); 26 HCM patients, seven genotype-positive, phenotype-negative individuals at risk of HCM (first-degree relatives) and nine healthy volunteers, underwent CMR to identify, and grade extent of, myocardial fibrosis and perfusion defect. 12-lead ECG was used for calculating the ECG risk-score (grading 0–14p). High-risk ECG (risk-score > 5p) occurred only in the HCM group (9/26), and the proportion was significantly higher vs mutation carriers combined with healthy volunteers (0/16, p = 0.008). Extent of LGE correlated to the ECG-score (R2 = 0.47, p = 0.001) in sarcomeric mutations. In low-risk ECG-score patients (0–2p), median percent of myocardium showing LGE (LGE%LVM) were: 0% [interquartile range, IQR, 0–0%], in intermediate-risk (3–5p): 5.4% [IQR 0–13.5%] and in high-risk (6–14p): 10.9% [IQR 4.2–12.3%]. ECG-score > 2p had a sensitivity and specificity of 79% and 84% to detect positive LGE on CMR and 77% vs. 75% to detect perfusion defects in sarcomeric mutations carriers. In patients with myocardial fibrosis as identified by LGE, median ECG risk-score was 8p [range 3–10p]. In conclusions, ECG risk-score > 2 p could be used as a cut-off for screening of myocardial fibrosis. Thus ECG risk-score is an inexpensive complementary tool in risk stratification of HCM in the young. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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99. ACE Genotype Distributions Differ between Sporadic and Familial Hypertrophic Cardiomyopathy
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Ara Kassarjian and Eleanor Elstein
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ace ,hcm ,cardiomyopathy ,genotype ,sporadic ,familial ,Medicine - Abstract
This study investigated the frequency of ACE genotypes in sporadic hypertrophic cardiomyopathy (HCM) and compared these frequencies to those found in the general population and in familial HCM. Delineation of the genotype of a 287 bp fragment in the ACE gene of 10 patients with confirmed sporadic HCM demonstrated that 2 (20%) were of the DD genotype, 5 (50%) of the ID genotype, and 3 (30%) of the II genotype. These genotype distributions did not differ significantly from controls (p < 0.57). Comparison of the present results with genotype frequencies in familial HCM reported in prior studies revealed a significant difference in genotype distribution between sporadic and familial HCM (p < 0.04). These findings indicate that the frequency of the ACE genotype does not appear to differ between patients with sporadic HCM and the general population. However, the results suggest that, with regard to the ACE polymorphism studied, genetic differences may exist between the sporadic and familial forms of HCM.
- Published
- 2020
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100. Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy.
- Author
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Oldach, Maureen S., Ueda, Yu, Ontiveros, Eric S., Fousse, Samantha L., Visser, Lance C., and Stern, Joshua A.
- Subjects
- *
HYPERTROPHIC cardiomyopathy , *DIASTOLE (Cardiac cycle) , *SYSTOLIC blood pressure , *CATS , *CONGESTIVE heart failure , *LEFT heart atrium - Abstract
Background: Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. Results: Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. Conclusions: In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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