Pubblicazioni recenti - hypertrophic cardiomyopathy
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Heart rate variability and haemodynamic function in individuals with hypertrophic cardiomyopathy.
Clin Physiol Funct Imaging2023 Jun;():. doi: 10.1111/cpf.12840.
Alyahya A I, Charman S J, Okwose N C, Fuller A S, Eggett C, Luke P, Bailey K, MacGowan G A, Jakovljevic D G,
Abstract
OBJECTIVES:
Heart rate variability (HRV) is a measure of cardiac autonomic function. This study: (1) evaluated the differences in HRV and haemodynamic function between individuals with hypertrophic cardiomyopathy (HCM) and healthy controls, and (2) determined the relationship between HRV and haemodynamic variables in individuals with HCM.
METHODS:
Twenty-eight individuals with HCM (n=7, females; age 54±15 years; body mass index: 29±5 kg/m ) and 28 matched healthy individuals (n=7 females; age 54±16 years; body mass index: 29±5 kg/m ) completed 5-minute HRV and haemodynamic measurements under resting (supine) conditions using bioimpedance technology. Frequency domain HRV measures (absolute and normalised low frequency power (LF), high frequency power (HF) and LF/HF ratio) and RR interval were recorded.
RESULTS:
Individuals with HCM demonstrated higher vagal activity (i.e., absolute unit of HF power (7.40±2.50 vs. 6.03±1.35 ms , p=0.01) but lower RR interval (914±178 vs. 1014±168 ms, p=0.03) compared to controls. Stroke volume (SV) index and cardiac index were lower in HCM compared to healthy individuals (SV, 33±9 vs. 43±7 ml?/beat?/m², p
CONCLUSIONS:
Short-term frequency domain indices of HRV provide a feasible approach to assess autonomic function in individuals with HCM. Vagal activity, represented by HF power, is increased, and associated with peripheral resistance in individuals with HCM. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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PCBP1 regulates alternative splicing of AARS2 in congenital cardiomyopathy.
bioRxiv2023 May;():. doi: 2023.05.18.540420.
Lu Yao Wei, Liang Zhuomin, Guo Haipeng, Fernandes Tiago, Espinoza-Lewis Ramon A, Wang Tingting, Li Kathryn, Li Xue, Singh Gurinder Bir, Wang Yi, Cowan Douglas, Mably John D, Philpott Caroline C, Chen Hong, Wang Da-Zhi,
Abstract
Alanyl-transfer RNA synthetase 2 (AARS2) is a nuclear encoded mitochondrial tRNA synthetase that is responsible for charging of tRNA-Ala with alanine during mitochondrial translation. Homozygous or compound heterozygous mutations in the Aars2 gene, including those affecting its splicing, are linked to infantile cardiomyopathy in humans. However, how Aars2 regulates heart development, and the underlying molecular mechanism of heart disease remains unknown. Here, we found that poly(rC) binding protein 1 (PCBP1) interacts with the Aars2 transcript to mediate its alternative splicing and is critical for the expression and function of Aars2. Cardiomyocyte-specific deletion of Pcbp1 in mice resulted in defects in heart development that are reminiscent of human congenital cardiac defects, including noncompaction cardiomyopathy and a disruption of the cardiomyocyte maturation trajectory. Loss of Pcbp1 led to an aberrant alternative splicing and a premature termination of Aars2 in cardiomyocytes. Additionally, Aars2 mutant mice with exon-16 skipping recapitulated heart developmental defects observed in Pcbp1 mutant mice. Mechanistically, we found dysregulated gene and protein expression of the oxidative phosphorylation pathway in both Pcbp1 and Aars2 mutant hearts; these date provide further evidence that the infantile hypertrophic cardiomyopathy associated with the disorder oxidative phosphorylation defect type 8 (COXPD8) is mediated by Aars2. Our study therefore identifies Pcbp1 and Aars2 as critical regulators of heart development and provides important molecular insights into the role of disruptions in metabolism on congenital heart defects.
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Reducing microtubule detyrosination improves heart function in HCM mice and human iPSC-engineered heart tissues.
bioRxiv2023 May;():. doi: 2023.05.25.542365.
Pietsch Niels, Chen Christina Yingxian, Kupsch Svenja, Bacmeister Lucas, Geertz Birgit, Herera-Rivero Marisol, Voß Hanna, Krämer Elisabeth, Braren Ingke, Westermann Dirk, Schlüter Hartmut, Mearini Giulia, Schlossarek Saskia, van der Velden Jolanda, Caporizzo Matthew A, Lindner Diana, Prosser Benjamin L, Carrier Lucie,
Abstract
RATIONALE:
Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular (LV) hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that ?-tubulin detyrosination (dTyr-tub) is markedly elevated in heart failure. Reduction of dTyr-tub by inhibition of the detyrosinase (VASH/SVBP complex) or activation of the tyrosinase (tubulin tyrosine ligase, TTL) markedly improved contractility and reduced stiffness in human failing cardiomyocytes, and thus poses a new perspective for HCM treatment.
OBJECTIVE:
In this study, we tested the impact of targeting dTyr-tub in a mouse model of HCM, the Mybpc3-targeted knock-in (KI) mice, and in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and engineered heart tissues (EHTs) deficient in SVBP or TTL.
METHODS AND RESULTS:
TTL gene transfer was tested in wild-type (WT) mice and rats and in adult KI mice. We show that i) TTL dose-dependently reduced dTyr-tub and improved contractility without affecting cytosolic calcium transients in WT cardiomyocytes; ii) TTL partially improved LV function and diastolic filling, reduced stiffness and normalized cardiac output and stroke volume in KI mice; iii) TTL induced a marked transcription and translation of several tubulins in KI mice; iv) TTL modulated mRNA or protein levels of components of mitochondria, Z-disc, ribosome, intercalated disc, lysosome and cytoskeleton in KI mice; v) SVBP-KO and TTL-KO EHTs exhibited low and high dTyr-tub levels, higher and lower force of contraction and enhanced and prolonged relaxation than in WT EHTs, respectively. RNA-seq and mass spectrometry analysis revealed distinct enrichment of cardiomyocyte components and pathways in SVBP-KO vs. TTL-KO EHTs.
CONCLUSION:
This study provides evidence that reducing dTyr-tub improves function in HCM mouse hearts and human EHTs and holds promise for targeting the non-sarcomeric cytoskeleton in heart disease.
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Identification and functional analysis of a novel de novo missense mutation located in the initiation codon of LAMP2 associated with early onset female Danon disease.
Mol Genet Genomic Med2023 Jun;():e2216. doi: 10.1002/mgg3.2216.
Wang Yongxiang, Bai Ming, Zhang Piyi, Peng Yu, Chen Zixian, He Zhiyu, Xu Jin, Zhu Youqi, Yan Dongdong, Wang Runqing, Zhang Zheng,
Abstract
BACKGROUND:
Danon disease is characterized by the failure of lysosomal biogenesis, maturation, and function due to a deficiency of lysosomal membrane structural protein (LAMP2).
METHODS:
The current report describes a female patient with a sudden syncope and hypertrophic cardiomyopathy phenotype. We identified the pathogenic mutations in patients by whole-exon sequencing, followed by a series of molecular biology and genetic approaches to identify and functional analysis of the mutations.
RESULTS:
Suggestive findings by cardiac magnetic resonance (CMR), electrocardiogram (ECG), and laboratory examination suggested Danon disease which was confirmed by genetic testing. The patient carried a novel de novo mutation, LAMP2 c.2T>C located at the initiation codon. The quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis of peripheral blood leukocytes from the patients revealed evidence of LAMP2 haploinsufficiency. Labeling of the new initiation codon predicted by the software with green fluorescent protein followed by fluorescence microscopy and Western blotting showed that the first ATG downstream from the original initiation codon became the new translational initiation codon. The three-dimensional structure of the mutated protein predicted by alphafold2 revealed that it consisted of only six amino acids and failed to form a functional polypeptide or protein. Overexpression of the mutated LAMP2 c.2T>C showed a loss of function of the protein, as assessed by the dual-fluorescence autophagy indicator system. The mutation was confirmed to be null, AR experiments and sequencing results confirmed that 28% of the mutant X chromosome remained active.
CONCLUSION:
We propose possible mechanisms of mutations associated with haploinsufficiency of LAMP2: (1) The inactivation X chromosome carrying the mutation was not significantly skewed. However, it decreased in the mRNA level and the expression ratio of the mutant transcripts; (2) The identified mutation is null, and the active mutant transcript fails to translate into the normal LAMP2 proteins. The presence of haploinsufficiency in LAMP2 and the X chromosome inactivation pattern were crucial factors contributing to the early onset of Danon disease in this female patient.
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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Treatment Strategies for Cardiomyopathy in Children: A Scientific Statement From the American Heart Association.
Circulation2023 Jun;():. doi: 10.1161/CIR.0000000000001151.
Bogle Carmel, Colan Steven D, Miyamoto Shelley D, Choudhry Swati, Baez-Hernandez Nathanya, Brickler Molly M, Feingold Brian, Lal Ashwin K, Lee Teresa M, Canter Charles E, Lipshultz Steven E, ,
Abstract
This scientific statement from the American Heart Association focuses on treatment strategies and modalities for cardiomyopathy (heart muscle disease) in children and serves as a companion scientific statement for the recent statement on the classification and diagnosis of cardiomyopathy in children. We propose that the foundation of treatment of pediatric cardiomyopathies is based on these principles applied as personalized therapy for children with cardiomyopathy: (1) identification of the specific cardiac pathophysiology; (2) determination of the root cause of the cardiomyopathy so that, if applicable, cause-specific treatment can occur (precision medicine); and (3) application of therapies based on the associated clinical milieu of the patient. These clinical milieus include patients at risk for developing cardiomyopathy (cardiomyopathy phenotype negative), asymptomatic patients with cardiomyopathy (phenotype positive), patients with symptomatic cardiomyopathy, and patients with end-stage cardiomyopathy. This scientific statement focuses primarily on the most frequent phenotypes, dilated and hypertrophic, that occur in children. Other less frequent cardiomyopathies, including left ventricular noncompaction, restrictive cardiomyopathy, and arrhythmogenic cardiomyopathy, are discussed in less detail. Suggestions are based on previous clinical and investigational experience, extrapolating therapies for cardiomyopathies in adults to children and noting the problems and challenges that have arisen in this experience. These likely underscore the increasingly apparent differences in pathogenesis and even pathophysiology in childhood cardiomyopathies compared with adult disease. These differences will likely affect the utility of some adult therapy strategies. Therefore, special emphasis has been placed on cause-specific therapies in children for prevention and attenuation of their cardiomyopathy in addition to symptomatic treatments. Current investigational strategies and treatments not in wide clinical practice, including future direction for investigational management strategies, trial designs, and collaborative networks, are also discussed because they have the potential to further refine and improve the health and outcomes of children with cardiomyopathy in the future.
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Clinical Significance of Physical Examination for Hypertrophic Cardiomyopathy.
Circ J2023 Jun;():. doi: 10.1253/circj.CJ-23-0131.
Kawasaki Tatsuya, Shiraishi Hirokazu, Matoba Satoaki,
Abstract
BACKGROUND:
Patients with hypertrophic cardiomyopathy (HCM) show various physical findings, but their clinical significance has not been systematically evaluated.Methods?and?Results: This study evaluated 105 consecutive patients with HCM who had undergone phonocardiography and external pulse recording. Physical examinations included a visible jugular a-wave (Jug-a), audible 4th sound (S4), and double or sustained apex beat. The primary outcome was a composite of all-cause death and hospitalization for cardiovascular disease. A total of 104 non-HCM subjects served as controls. The prevalence of visible Jug-a in the seated or supine position, audible S4, and a sustained or double apex beat in patients with HCM were 10%, 71%, 70%, 42%, and 27%, respectively, all of which were significantly higher than in the controls (0%, 20%, 11%, 17%, and 2%; P
CONCLUSIONS:
Detection of these findings has clinical importance in the diagnosis and risk stratification of HCM prior to the use of advanced imaging techniques.
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Risk factors of sudden cardiac death in Egyptian patients younger than 40 years.
Egypt Heart J2023 Jun;75(1):45. doi: 45.
Ali Ahmed Nabil, Abdeltawab Hend Ali, Eldamanhoury Hayam, Aboulmaaty Mervat,
Abstract
BACKGROUND:
Sudden cardiac death in young people is a major problem. The causes are well known; however, they may not be discovered before the episode of sudden death. A challenge for the future is identifying patients at risk before an episode of sudden cardiac death. Development of preventive and educational programs is required to identify sudden cardiac death/sudden cardiac arrest (SCD/SCA) risk factors, causes and characteristics. We aimed to study the characteristics of SCD/SCA in a cohort of young Egyptian population. Our retrospective cohort study included 246 patients of SCD/SCA who were collected from 5000 records of arrhythmia patients from January 2010 till January 2020. The records of the specialized arrhythmia clinic were reviewed to collect the families of SCD/SCA. All patients and/or their first-degree relatives were subjected to thorough history taking and clinical evaluation and investigations. Comparisons were done regarding age group and presence of positive family history of SCD.
RESULTS:
Males constituted 56.9% of the study population. Mean age was 26.6?±?12.73 years. Positive family history was present in 202 (82.1%) cases. Sixty-one percent of the cases had history of syncopal attacks. SCD/SCA during non-exertion or sleep occurred in 50.4% of cases. Hypertrophic cardiomyopathy was the most common cause of SCD/SCA (20.3%), followed by dilated cardiomyopathy (19.1%), long QT Syndrome (11.4%), complete heart block (8.5%), and Brugada syndrome (6.8%). In the older age group of 18-40 years, hypertrophic cardiomyopathy was responsible for SCD in 44 patients (25.3%) versus 6 patients (8.3%) in younger age group (p-value: 0.003). DCM was also dominant in older age group (42 patients; 24.1%) versus 5 patients (6.9%) in younger age group. Hypertrophic cardiomyopathy was more prevalent in positive family history group (46 patients; 22.8%) versus 4 patients (9.1%) in negative family history group (p-value: 0.041).
CONCLUSION:
Family history of SCD was the most common risk factor of SCD. The most common cause of SCD in young Egyptian patients below 40 years was hypertrophic cardiomyopathy, followed by dilated cardiomyopathy. Both diseases were more common in the age group between 18 and 40 years. Hypertrophic cardiomyopathy was more common in patients with positive family history of SCD/SCA.
© 2023. The Author(s).
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Proteomic profiling of sudden cardiac death with acquired cardiac hypertrophy.
Int J Legal Med2023 Jun;():. doi: 10.1007/s00414-023-03038-6.
Kakimoto Yu, Ueda Atsushi, Ito Masatoshi, Tanaka Masayuki, Kubota Tomoko, Isozaki Shotaro, Osawa Motoki,
Abstract
BACKGROUND:
Cardiac hypertrophy, which develops in middle-aged and older individuals as a consequence of hypertension and obesity, is an established risk factor for sudden cardiac death (SCD). However, it is sometimes difficult to differentiate SCD with acquired cardiac hypertrophy (SCH) from compensated cardiac hypertrophy (CCH), at autopsy. We aimed to elucidate the proteomic alteration in SCH, which can be a guideline for future postmortem diagnosis.
METHODS:
Cardiac tissues were sampled at autopsy. SCH group consisted of ischemic heart failure, hypertensive heart failure, and aortic stenosis. CCH group included cases of non-cardiac death with cardiac hypertrophy. The control group comprised cases of non-cardiac death without cardiac hypertrophy. All patients were aged?>?40 years, and hypertrophic cardiomyopathy was not included in this study. We performed histological examination and shotgun proteomic analysis, followed by quantitative polymerase chain reaction analysis.
RESULTS:
Significant obesity and myocardial hypertrophy, and mild myocardial fibrosis were comparable in SCH and CCH cases compared to control cases. The proteomic profile of SCH cases was distinguishable from those of CCH and control cases, and many sarcomere proteins were increased in SCH cases. Especially, the protein and mRNA levels of MYH7 and MYL3 were significantly increased in SCH cases.
CONCLUSION:
This is the first report of cardiac proteomic analysis in SCH and CCH cases. The stepwise upregulation of sarcomere proteins may increase the risk for SCD in acquired cardiac hypertrophy before cardiac fibrosis progresses significantly. These findings can possibly aid in the postmortem diagnosis of SCH in middle-aged and older individuals.
© 2023. The Author(s).
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A foundational vision transformer improves diagnostic performance for electrocardiograms.
NPJ Digit Med2023 Jun;6(1):108. doi: 108.
Vaid Akhil, Jiang Joy, Sawant Ashwin, Lerakis Stamatios, Argulian Edgar, Ahuja Yuri, Lampert Joshua, Charney Alexander, Greenspan Hayit, Narula Jagat, Glicksberg Benjamin, Nadkarni Girish N,
Abstract
The electrocardiogram (ECG) is a ubiquitous diagnostic modality. Convolutional neural networks (CNNs) applied towards ECG analysis require large sample sizes, and transfer learning approaches for biomedical problems may result in suboptimal performance when pre-training is done on natural images. We leveraged masked image modeling to create a vision-based transformer model, HeartBEiT, for electrocardiogram waveform analysis. We pre-trained this model on 8.5 million ECGs and then compared performance vs. standard CNN architectures for diagnosis of hypertrophic cardiomyopathy, low left ventricular ejection fraction and ST elevation myocardial infarction using differing training sample sizes and independent validation datasets. We find that HeartBEiT has significantly higher performance at lower sample sizes compared to other models. We also find that HeartBEiT improves explainability of diagnosis by highlighting biologically relevant regions of the EKG vs. standard CNNs. Domain specific pre-trained transformer models may exceed the classification performance of models trained on natural images especially in very low data regimes. The combination of the architecture and such pre-training allows for more accurate, granular explainability of model predictions.
© 2023. The Author(s).
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Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.
J Cardiovasc Transl Res2023 Jun;():. doi: 10.1007/s12265-023-10398-2.
Jansen Mark, Schmidt A F, Jans J J M, Christiaans I, van der Crabben S N, Hoedemaekers Y M, Dooijes D, Jongbloed J D H, Boven L G, Lekanne Deprez R H, Wilde A A M, van der Velden J, de Boer R A, van Tintelen J P, Asselbergs F W, Baas A F,
Abstract
Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G?+?P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G?+?P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G?+?P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p?=?0.005 and coefficient 0.803, p?=?0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p?=?0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.
© 2023. The Author(s).
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Anaesthetic management of thyroid storm in a patient with Friederich's ataxia. A case report.
Rev Esp Anestesiol Reanim (Engl Ed)2023 Jun;():. doi: S2341-1929(23)00096-3.
Sneyers Closa M, Pérez Requena A, Sánchez García S, Sistac Ballarín J,
Abstract
A 26-year-old patient with Friederich's ataxia with hypertrophic obstructive cardiomyopathy undergoing total thyroidectomy due to persistent amiodarone-induced thyrotoxicosis (despite high doses of antithyroid drugs and corticosteroids), presented an intraoperative episode suggestive of thyroid storm. Thyroid storm is an endocrine emergency that is associated with high morbidity and mortality. Early diagnosis and treatment, which is of vital importance to improve survival, includes symptomatic treatment, treatment of cardiovascular, neurological, and/or hepatic manifestations and thyrotoxicosis, measures to suppress or avoid triggering stimuli, and definitive treatment.
Copyright © 2023 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
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Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy.
Expert Opin Pharmacother2023 Jun;():1-12. doi: 10.1080/14656566.2023.2219840.
Rosenzveig Akiva, Garg Neil, Rao Shiavax J, Kanwal Amreen K, Kanwal Arjun, Aronow Wilbert S, Martinez Matthew W,
Abstract
INTRODUCTION:
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic causes of heart disease. Since the initial description of HCM, there have been minimal strides in management options. Obstructive HCM constitutes a larger subset of patients with increased left ventricular outflow tract gradients causing symptoms. Septal reduction therapy (SRT) has been successful, but it is not the answer for all patients and is not disease modifying.
AREAS COVERED:
Current guideline recommendations include beta-blockers, calcium channel blockers, or disopyramides for medical management, but there lacks evidence of much benefit with these drugs. In recent years, there has been the emergence of cardiac myosin inhibitors (CMI) which have demonstrated positive results in patients with both obstructive and non-obstructive HCM. In addition to CMIs, other drugs have been investigated as we have learned more about HCM's pathological mechanisms. Drugs targeting sodium channels and myocardial energetics, as well as repurposed drugs that have demonstrated positive remodeling are being investigated as potential therapeutic targets. Gene therapy is being explored with vast potential for the treatment of HCM.
EXPERT OPINION:
The armamentarium of therapeutic options for HCM is continuously increasing with the emergence of CMIs as mainstays of treatment. The future of HCM treatment is promising.
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A pathogenic nonsense mutation (c.1522C>T) of the MYBPC3 gene is implicated with hypertrophic cardiomyopathy.
ESC Heart Fail2023 Jun;():. doi: 10.1002/ehf2.14424.
Ni Erru, Wang Tao, Zhang Xuan, Xie Huabin,
Abstract
Hypertrophic cardiomyopathy (HCM), a genetically and clinically heterogeneous cardiomyopathy, is commonly caused by mutations in the MYBPC3 gene or other various sarcomeric genes. HCM patients carrying sarcomeric gene mutations may experience an asymptomatic period at early stage but still possess an escalating risk of developing adverse cardiac events including sudden cardiac death. It is crucial to determine the phenotypic and pathogenic effects of mutations in sarcomeric genes. In this study, a 65-year-old male was admitted with a history of chest pain, dyspnoea, and syncope and with a family history of HCM and sudden cardiac death. On admission, electrocardiogram indicated atrial fibrillation and myocardial infarction. Transthoracic echocardiography revealed left ventricular concentric hypertrophy and systolic dysfunction (48%), which were ascertained by cardiovascular magnetic resonance. With late gadolinium-enhancement imaging, cardiovascular magnetic resonance found myocardial fibrosis on left ventricular wall. The exercise stress echocardiography test showed non-obstructive myocardial changes. Whole-exome sequencing analysis identified a MYBPC3 gene heterozygous nonsense variant (c.1522C>T) in the patient and one of his healthy grandnieces (18-year-old). The patient was diagnosed with non-obstructive HCM, heart failure, atrial fibrillation, and so on. Medications, ICD implantation, and catheter ablation were chosen to maintain heart function. Our study provides the clinical evidence regarding the HCM pathogenicity of MYBPC3 c.1522C>T variant and highlights the significance of family genetic testing in the diagnosis and management of HCM.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Cardiomyopathy-associated variants alter the structure and function of the ?-actinin-2 actin-binding domain.
Biochem Biophys Res Commun2023 May;670():12-18. doi: 10.1016/j.bbrc.2023.05.050.
Atang Alexandra E, Rebbeck Robyn T, Thomas David D, Avery Adam W,
Abstract
Hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM) are characterized by thickening, thinning, or stiffening, respectively, of the ventricular myocardium, resulting in diastolic or systolic dysfunction that can lead to heart failure and sudden cardiac death. Recently, variants in the ACTN2 gene, encoding the protein ?-actinin-2, have been reported in HCM, DCM, and RCM patients. However, functional data supporting the pathogenicity of these variants is limited, and potential mechanisms by which these variants cause disease are largely unexplored. Currently, NIH ClinVar lists 34 ACTN2 missense variants, identified in cardiomyopathy patients, which we predict are likely to disrupt actin binding, based on their localization to specific substructures in the ?-actinin-2 actin binding domain (ABD). We investigated the molecular consequences of three ABD localized, HCM-associated variants: A119T, M228T and T247 M. Using circular dichroism, we demonstrate that the mutant ABD proteins can attain a well-folded state. However, thermal denaturation studies show that all three mutations are destabilizing, suggesting a structural disruption. Importantly, A119T decreased actin binding, and M228T and T247M cause increased actin binding. We suggest that altered actin binding underlies pathogenesis for cardiomyopathy mutations localizing to the ABD of ?-actinin-2.
Copyright © 2023 Elsevier Inc. All rights reserved.
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Incessant septal ventricular tachycardia in patient with hypertrophic cardiomyopathy after failed unipolar and bipolar ablation. Is ethanol septal ablation a solution?
Kardiol Pol -
Ventricular pre-excitation in cats: 17 cases.
J Vet Cardiol2023 Apr;47():70-82. doi: 10.1016/j.jvc.2023.04.005.
Sidler M, Santarelli G, Kovacevic A, Novo Matos J, Schreiber N, Baron Toaldo M,
Abstract
OBJECTIVES:
Atrioventricular accessory pathways are abnormal electrical connections between the atria and ventricles that predispose to ventricular pre-excitation (VPE) and tachycardias.
ANIMALS:
Seventeen cats with VPE and 15 healthy matched-control cats.
MATERIAL AND METHODS:
Multicenter case-control retrospective study. Clinical records were searched for cats with VPE, defined as preserved atrioventricular synchrony, reduced PQ interval, and increased QRS complex duration with a delta wave. Clinical, electrocardiography, echocardiographic, and outcome data were collated.
RESULTS:
Most cats with VPE were male (16/17 cats), non-pedigree cats (11/17 cats). Median age and mean body weight were 5.4 years (0.3-11.9 years) and 4.6 ± 0.8 kg, respectively. Clinical signs at presentation included lethargy (10/17 cats), tachypnea (6/17 cats), and/or syncope (3/17 cats). In two cats, VPE was an incidental finding. Congestive heart failure was uncommon (3/17 cats). Nine (9/17) cats had tachyarrhythmias: 7/9 cats had narrow QRS complex tachycardia and 2/9 cats had wide QRS complex tachycardia. Four cats had ventricular arrhythmias. Cats with VPE had larger left (P
CONCLUSIONS:
Cats with VPE had a relatively long survival, albeit showing larger atria and thicker left ventricular walls than healthy cats.
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
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Outcomes of concomitant surgical ablation in patients undergoing surgical myectomy for hypertrophic obstructive cardiomyopathy: A systematic review and meta-analysis.
Int J Cardiol2023 May;():. doi: S0167-5273(23)00743-X.
Kharbanda Rohit K, Ramdat Misier Nawin L, Van den Eynde Jef, El Mathari Sulayman, Tom?i? Anton, Palmen Meindert, Klautz Robert J M,
Abstract
OBJECTIVE:
Studies investigating the efficacy of concomitant surgical atrial fibrillation (AF) ablation in hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing myectomy are scarce and limited in terms of sample size. We aim to summarize current outcomes of concomitant surgical AF ablation in HOCM patients undergoing surgical myectomy.
METHODS:
This systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included all studies reporting any of the following outcomes of concomitant surgical AF ablation in HOCM patients: freedom from recurrence of AF, overall survival and complications. Outcomes were evaluated using traditional meta-analysis at given time-points and using pooled Kaplan-Meier curves.
RESULTS:
A total of 13 studies were included, resulting in a total of 616 individual patients available for analysis. AF was paroxysmal in 68.1% of the patients (95% CI 56.0-78.2%; I?=?87.1%; 8 studies, 583 participants). The majority of patients (86.2%) underwent either conventional Cox Maze III or IV (95% CI 39.7-98.3%; I?=?92.4%; 8 studies, 616 patients) procedure. The incidence of early post-operative pacemaker implantation was 6.1% (95% CI 3.1-11.8%). Overall survival at 3, 5 and 7?years was 95.6% (95% CI 93.4-97.9%), 93.6% (95% CI 90.8-96.5%) and 90.5% (95% CI 86.5-94.6%), respectively. Freedom from recurrent AF at 3, 5 and 7?years was 77.6% (95% CI 73.7-81.7%), 70.6% (95% CI 65.8-75.7) and 63.2% (95% CI 56.2-73.8%), respectively.
CONCLUSION:
This meta-analysis supports concomitant surgical AF ablation at the time of surgical myectomy in HOCM patients, as it seems to be safe and effective in terminating AF.
Copyright © 2023. Published by Elsevier B.V.
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Serum Proteomic Signatures in Umbilical Cord Blood of Preterm Neonates Delivered by Women with Gestational Diabetes.
Diabetes Metab Syndr Obes2023 ;16():1525-1539. doi: 10.2147/DMSO.S406297.
Li Xiaoyan, Zhang Bin, Ding Wen, Jia Xianfen, Han Zhen, Zhang Lin, Hu Yifeng, Shen Bing, Wang Huiqin,
Abstract
BACKGROUND:
Women who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development.
MATERIALS AND METHODS:
Umbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography-tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs.
RESULTS:
We found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay.
CONCLUSION:
Our proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.
© 2023 Li et al.
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Effects of bariatric surgery on cardiovascular-related acute care use in patients with hypertrophic cardiomyopathy.
ESC Heart Fail2023 May;():. doi: 10.1002/ehf2.14414.
Miyashita Satoshi, Akita Keitaro, Zhao Yanling, Hasegawa Kohei, Maurer Mathew S, Weiner Shepard D, Reilly Muredach P, Takayama Hiroo, Shimada Yuichi J,
Abstract
AIMS:
Prior studies have suggested causal relationships between obesity and acute cardiovascular events. It has been also known that the risk of acute cardiovascular events is reduced by bariatric surgery. However, little is known about whether bariatric surgery lowers the risk of acute cardiovascular events in patients with obesity and hypertrophic cardiomyopathy (HCM). In this context, we aimed to investigate whether bariatric surgery is associated with a reduced risk of cardiovascular-related acute care use in patients with HCM.
METHODS AND RESULTS:
In this population-based study, the bariatric surgery group consisted of patients with HCM who underwent bariatric surgery from January 2004 to December 2014. The control group included those who have obesity and HCM and received non-bariatric elective intra-abdominal surgery during the same period. The outcome was cardiovascular-related acute care use (i.e. emergency department (ED) visits or unplanned hospitalizations for cardiovascular disease) during a 1-year post-surgery period. We used the SPARCS database, a population-based ED and inpatient database in New York State. We constructed logistic regression models with generalized estimating equations to compare the risk of the outcome events during sequential 6-month post-surgery periods. We adjusted for age, sex, number of ED visits and hospitalizations for cardiovascular disease within 2 years before the index surgery, and the Elixhauser co-morbidity measures. We also performed propensity score (PS)-matching and inverse probability treatment weighting analyses using these variables. The analytic cohort consisted of 207 adults with obesity and HCM, including 147 patients who underwent bariatric surgery and 60 in the control group. The risk was not significantly different in the 1-6 months post-surgery period. By contrast, in the 7-12 months post-surgery period, the risk of cardiovascular-related acute care use was significantly lower in the bariatric surgery group (adjusted odds ratio 0.23; 95% CI 0.068-0.71; P = 0.01) compared with the control group. In the PS-matched cohort, there were no significant differences in the baseline characteristics. The PS-matched analysis demonstrated lower risk of the outcome event in the bariatric surgery group in the 7-12 months post-surgery period. The inverse probability treatment weighting analysis replicated the findings.
CONCLUSIONS:
Bariatric surgery was associated with a lower risk of cardiovascular-related acute care use in the 7-12 months post-surgery period in this population-based study.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Narrative Review of Anomalous origin of coronary arteries: Pathophysiology, Management, and Treatment.
Curr Cardiol Rev2023 May;():. doi: 10.2174/1573403X19666230530095341.
Kanagala Sai Gautham, Gupta Vasu, Dunn Garrett V, Kaur Harmanjit, Zeineddine Farid, Jain Rohit, Garg Nikita,
Abstract
Coronary artery anomalies (CAA) are a diverse group of congenital anomalies and are the second most common cause of sudden cardiac death in the young population after Hypertrophic Cardiomyopathy (HCM). Symptoms range from chest pain, syncope, or sudden cardiac arrest to completely asymptomatic. The prevalence of congenital coronary artery anomalies in the general population is estimated to be between 1% and 2%. CAA often gets underdiagnosed due to the lack of knowledge of the disease process. Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease or luminal narrowing due to other causes. Congenital coronary artery anomalies account for 50-60% of this 5% of patients. Most patients are asymptomatic for most of their lives, and chest pain is the most common symptom in symptomatic patients when referred for coronary angiography, typically when the diagnosis is typically made. The malignant coronary artery is a rare presentation of a coronary anomaly when associated with atherosclerotic coronary artery disease or valvular heart disease. Patients with symptoms of an abnormal coronary artery origin will receive medical treatment/observation, exercise restriction, coronary angioplasty with stent deployment, or surgical repair.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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