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Pubblicazioni recenti - dilated cardiomyopathy
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Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.
Elife2021 Sep;10():. doi: 10.7554/eLife.58313.
Filomena Maria Carmela, Yamamoto Daniel L, Carullo Pierluigi, Medvedev Roman, Ghisleni Andrea, Piroddi Nicoletta, Scellini Beatrice, Crispino Roberta, D'Autilia Francesca, Zhang Jianlin, Felicetta Arianna, Nemska Simona, Serio Simone, Tesi Chiara, Catalucci Daniele, Linke Wolfgang A, Polishchuk Roman, Poggesi Corrado, Gautel Mathias, Bang Marie-Louise,
Abstract
Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. gene mutations are causative for dilated (DCM), hypertrophic and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca release and reuptake in unstressed MKO mice as well as reduced Ca spark amplitude post-TAC, suggesting that altered Ca handling may contribute to the development of DCM in MKO mice.
© 2021, Filomena et al.
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CSRP3, p.Arg122*, is Responsible for Hypertrophic Cardiomyopathy in a Chinese Family.
J Gene Med2021 Sep;():e3390. doi: 10.1002/jgm.3390.
Huang Hao, Chen Yaqin, Jin Jieyuan, Du Ran, Tang Ke, Fan Liangliang, Xiang Rong,
Abstract
BACKGROUND:
Hypertrophic cardiomyopathy (HCM) is a hereditary disease manifested by a thickened ventricular wall. Cysteine and glycine-rich protein 3 (CSRP3), the gene encoding muscle LIM protein, is important to initiate hypertrophic gene expression. The mutation of CSRP3 is proved to cause dilated cardiomyopathy (DCM) or HCM.
METHODS:
Herein, we enrolled a Chinese family with HCM across three generations. Whole-exome sequencing (WES) was performed in the proband to detect the candidate genes of the family. Sanger sequence was performed for mutational analysis and confirmation of cosegregation.
RESULTS:
Through histopathological and imaging examinations, an obvious left ventricular hypertrophy was found in the proband. After WES data filtering, bioinformatic prediction and co-segregation analysis, a nonsense mutation (NM_003476.5:c.364C>T; NP_003467.1:p.Arg122*) of CSRP3 was identified in this family. This variant was predicted to be disease-causing and resulted in a truncated protein.
CONCLUSIONS:
This is the first HCM family case of CSRP3 (p.Arg122*) variation in Asia. The finding here not only contributes to the genetic diagnosis and counseling of the family, but also provides a new case with detailed phenotypes that may be caused by the CSRP3 variant.
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Dilated right heart in a young lady with syncope: atrial septal defect masquerading as arrhythmogenic right ventricular cardiomyopathy.
Eur Heart J Case Rep2021 Sep;5(9):ytab274. doi: 10.1093/ehjcr/ytab274.
Shenoy Sundeep, Janardhanan Rajesh,
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Case report of Barth syndrome: a forgotten cause of cardiomyopathy.
Eur Heart J Case Rep2021 Jul;5(7):ytab195. doi: 10.1093/ehjcr/ytab195.
Rao Shiavax, Kanwal Arjun, Padmanabhan Sriram,
Abstract
Background:
Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and exercise intolerance. It is often considered to be a paediatric disease, owing to most cases being diagnosed during childhood and mortality being the highest during the first few years of life.
Case summary:
We report a case of dilated cardiomyopathy due to BTHS in a 27-year-old adult male patient, who initially presented with lightheadedness, dyspnoea, orthopnoea, and bilateral lower extremity oedema. Key findings from investigations included leukopenia, prolonged QTc interval, reduced left ventricular ejection fraction (LVEF), global enlargement of all heart chambers, patent coronary arteries, and mild pulmonary hypertension. The patient was diuresed to euvolemia and discharged with a LifeVest. Guideline-directed medical therapy was initiated and uptitrated as an outpatient. A repeat echocardiogram 2?years after initial presentation showed marked improvement in LVEF.
Discussion:
It is possible that there are adult patients with idiopathic cardiomyopathy, which may be attributable to BTHS. In the absence of an obvious underlying cause, with the appropriate historical information, clinical exam, laboratory investigations, and imaging findings, BTHS should be considered as a likely cause of non-ischaemic cardiomyopathy.
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Metabolic Processes are Potential Biological Processes Distinguishing Nonischemic Dilated Cardiomyopathy from Ischemic Cardiomyopathy: A Clue from Serum Proteomics.
Pharmgenomics Pers Med2021 ;14():1169-1184. doi: 10.2147/PGPM.S323379.
Huang Guangyong, Huang Zhiqi, Peng Yunling, Wang Yuehai, Liu Weitao, Xue Yuzeng, Yang Wenbo,
Abstract
Background:
Ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM) are the two most common causes of heart failure. However, our understanding of the specific proteins and biological processes distinguishing DCM from ICM remains insufficient.
Materials and Methods:
The proteomics analyses were performed on serum samples from ICM (n=5), DCM (n=5), and control (n=5) groups. Proteomics and bioinformatics analyses, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA), were performed to identify the hub circulating proteins and the hub biological processes in ICM and DCM.
Results:
The analysis of differentially expressed proteins and WGCNA identified the hub circulating proteins in ICM (GAPDH, CLSTN1, VH3, CP, and ST13) and DCM (one downregulated protein, FGG; 18 upregulated proteins, including HEL-S-276, IGK, ALDOB, HIST1H2BJ, HEL-S-125m, RPLP2, EL52, NCAM1, P4HB, HEL-S-99n, HIST1H4L, HIST2H3PS2, F8, ERP70, SORD, PSMA3, PSMB6, and PSMA6). The mRNA expression of the heart specimens from GDS651 validated that ALDOB, GAPDH, RPLP2, and IGK had good abilities to distinguish DCM from ICM. In addition, GSEA results showed that cell proliferation and differentiation were the hub biological processes related to ICM, while metabolic processes and cell signaling transduction were the hub biological processes associated with DCM.
Conclusion:
The present study identified five dysregulated hub circulating proteins among ICM patients and 19 dysregulated hub circulating proteins among DCM patients. Cell proliferation and differentiation were significantly enriched in ICM. Metabolic processes were strongly enhanced in DCM and may be used to distinguish DCM from ICM.
© 2021 Huang et al.
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Loss of eEF1A2 (Eukaryotic Elongation Factor 1 A2) in Murine Myocardium Results in Dilated Cardiomyopathy.
Circ Heart Fail2021 Sep;():CIRCHEARTFAILURE121008665. doi: 10.1161/CIRCHEARTFAILURE.121.008665.
Feng Wei, Wang Li, Veevers Jennifer, Liu Canzhao, Huang Titania, Chen Ju,
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Acute heart failure with dilated cardiomyopathy as the first manifestation of eosinophilic granulomatosis with polyangiitis.
J Eur Acad Dermatol Venereol2021 Sep;():. doi: 10.1111/jdv.17693.
Chen Y T, Liu W S, Su K Y, Hsu Y H, Chang C H,
Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a rare disease with necrotising vasculitis, occurring exclusively among patients with asthma and eosinophilia. Antineutrophil cytoplasmic antibody (ANCA)-positive patients with predominant 'vasculitic' manifestations more frequently exhibit peripheral nerve, renal, and skin involvement, while ANCA-negative patients with prominent 'eosinophilic' manifestations more commonly demonstrate cardiac and lung involvement.
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Cardiac resynchronization performed by LBBaP-CRT in patients with cardiac insufficiency and left bundle branch block.
Ann Noninvasive Electrocardiol2021 Sep;():e12898. doi: 10.1111/anec.12898.
Zu Linna, Zhang Junmeng, Wang Zefeng, Hang Fei, Jiang Yang, Wang Xinlu, Cheng Liting, Wu Yongquan,
Abstract
OBJECTIVE:
To evaluate the efficacy and safety of left bundle branch area pacing (LBBaP) in patients with heart failure and left bundle branch block (LBBB), and to compare the clinical effects with traditional cardiac resynchronization therapy (CRT).
METHODS:
Thirty-two patients with dilated cardiomyopathy complicated by cardiac insufficiency and left bundle branch block were divided into CRT group and LBBaP group. Parameters including pacing threshold, R-wave amplitude, pacing impedance and operation time, and X-ray exposure time were recorded. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) were examined by echocardiography. The changes of QRS complex before and after operation were compared.
RESULTS:
Compared with CRT group, the LBBaP group spent less time on total operation time and X-ray exposure time and had stable electrode parameters including pacing threshold, R-wave amplitude, and lead impedance after 12-month follow-up. In addition, LBBaP can achieve narrow QRS complex (117.15 ± 9.91) ms immediately than that in CRT group (130.32 ± 12.41) ms. The change of QRS between LBBaP is (50.30 ± 23.79) ms and CRT group is (33.15 ± 20.22) ms. After 6 months' follow-up in LBBaP group, EF was higher than that before operation. Followed up for 12 months after operation, EF and LVEDD in LBBaP group were significantly improved compared with those before operation.
CONCLUSION:
Left bundle branch area pacing is a safe and effective resynchronization method for patients with cardiac insufficiency and asynchronization, which can achieve same clinical effects to CRT.
© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.
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[Clinical and anamnestic characteristics of patients with an implanted cardioverter-defibrillator in real clinical practice (data from the Kuzbass register)].
Kardiologiia2021 Aug;61(8):40-47. doi: 10.18087/cardio.2021.8.n1651.
Lebedeva N B, Talibullin I V, Temnikova T B, Mamchur S E, Barbarash O L,
Abstract
Aim To study the consistency of the practice of management, selection and routing of patients at high risk of sudden cardiac death (SCD) selected for cardioverter-defibrillator implantation (CDI) with current clinical guidelines and to evaluate the quality of subsequent outpatient follow-up and treatment based on a retrospective analysis of clinical amnestic data from the Kuzbass Registry of Patients with CDI.Material and methods The study was based on the Registry of Patients with Implanted Cardioverter Defibrillator and included successive data of 28 patients hospitalized to the Kizbass Cardiological Center from 2015 through 2019. Social and clinical amnestic characteristics, indications for CVI, and concomitant drug therapy were analyzed retrospectively. Statistical analyses were performed with the Statistica 10.0 software (Statsoft, USA).Results Median age of patients was 59 (53; 66) years; 239 (83.6?%) men were included; 29 (10.1%) people were employed, CHI was performed in 182 (63.6?%) patients for prevention of SCC, and for secondary prevention in 104 (36.4?%) patients. 208 (72.7?%) patients were diagnosed with ischemic heart disease (IHD), and 145 (67.9?%) of them underwent myocardial revascularization. Noncoronarogenic diseases were found in 78 (27.3?%) patients, and most of them were diagnosed with dilated cardiomyopathy. All patients had chronic heart failure (CHF); half of them had stage IIA CHF. Median left ventricular ejection fraction was 30 (25; 36,5) % according to echocardiography using the Simpson method. Comorbidity was found in 151 (52.8?%) patients. 128 (44.8%) patients received a triple neurohormonal blockade for CHF treatment; titration to target doses was not performed in any of them. Antiarrhythmics were administered to 150 (52.4?%) patients.Conclusion According to the data from the Kuzbass Registry of CVI, the main patient cohort consisted of men of pension age with IHD and CHF. Before CVI, more than a half of them had not received an optimum drug therapy and not all of them had received target lesion revascularization. Creating and analysis of Registries of CHI patients is an effective method for identifying existing problems in patient management before CVI and for optimizing their subsequent follow-up and treatment.
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Electrocardiographic Changes in Dengue Fever: A Review of Literature.
Int J Gen Med2021 ;14():5607-5614. doi: 10.2147/IJGM.S328755.
Parchani Ashwin, Krishnan Vs Gokul, Kumar V K Sunil,
Abstract
Dengue fever is a prevalent viral disease that primarily affects tropical nations. Although most symptomatic infections have a relatively benign course, a small percentage of patients experience severe clinical symptoms, such as bleeding and endothelial dysfunction, which can lead to hypovolemic shock and cardiovascular collapse. Dengue fever is now known to involve the heart by inducing myocardial inflammation, arrhythmias, and, in rare cases, fulminant myocarditis, up to 13% in severe dengue. Conduction abnormalities can range from benign sinus bradycardia to fulminant tachyarrhythmias and atrioventricular blocks. Although most conduction disturbances are benign and transient, they can occasionally aggravate pre-existing conditions and even be fatal. Unlike other viral myocarditis like hepatitis C induced myocarditis, dengue causes mainly transient changes, and long-term complications like dilated cardiomyopathy are not noted. There is indeed a paucity of data on how to assess and treat individuals with conduction abnormalities. In this review, the authors have discussed the wide variety of conduction abnormalities seen in dengue, their pathophysiology, clinical consequences, and a method for evaluating and managing these individuals.
© 2021 Parchani et al.
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Autoinflammation leading to autoimmunity in adult-onset Still's disease: more than simple coincidence?
Eur J Med Res2021 Sep;26(1):110. doi: 10.1186/s40001-021-00581-z.
Valor-Méndez Larissa, Manger Bernhard, Cavallaro Alexander, Achenbach Stephan, Schett Georg, Rech Jürgen,
Abstract
BACKGROUND:
Adult-onset Still's disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation.
CASE PRESENTATION:
We report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman-Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease.
CONCLUSIONS:
Only two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -?1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.
© 2021. The Author(s).
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Description of breed ancestry and genetic health traits in arctic sled dog breeds.
Canine Med Genet2021 Sep;8(1):8. doi: 10.1186/s40575-021-00108-z.
Thorsrud Joseph A, Huson Heather J,
Abstract
BACKGROUND:
This study describes the presence and frequency of health traits among three populations of dogs traditionally used for sledding and explores their ancestry and breed composition as provided by the commercially available Embark dog DNA test. The three populations include the purebred Siberian Husky and the admixed populations of Alaskan sled dogs and Polar Huskies. While the Siberian Husky represents a well-established breed with extensive historical and health data, the Alaskan sled dog is less studied but has been the subject of nutritional, physiological, and genetic studies related to ancestry and performance. In contrast, the Polar Husky is a relatively obscure and rare group of dogs used for arctic exploration with very little-known information. The three populations were compared using Embark results, providing new insight into the health traits circulating within the populations and the potential ancestral linkage of the health traits between the sledding populations. Embark results are based upon 228,588 single-nucleotide polymorphisms (SNPs) spanning the canine genome, characterized using a custom-designed Illumina beadchip array.
RESULTS:
Specifically, breed composition was summarized for the two admixed populations with most of the dogs being predominantly categorized as Alaskan husky- type dog or "Supermutt". Mitochondrial and Y chromosome haplogroups and haplotypes were found with Alaskan sled dogs carrying most of the haplogroups and types found in Siberian and Polar Huskies. Genomic principal component analysis reflected population structure corresponding to breed and substructure within the Alaskan sled dogs related to sprint or distance competition. Genetic markers associated with Alanine Aminotransferase activity, Alaskan Husky Encephalopathy, dilated cardiomyopathy, Collie eye anomaly, degenerative myelopathy, ichthyosis, and factor VII deficiency were identified in the populations of sledding breeds.
CONCLUSION:
These results provide a preliminary description of genetic characteristics found in sledding breeds, improving the understanding and care of working sled dogs.
© 2021. The Author(s).
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Obesity modifies the energetic phenotype of dilated cardiomyopathy.
Eur Heart J2021 Sep;():. doi: ehab663.
Rayner Jennifer J, Peterzan Mark A, Clarke William T, Rodgers Christopher T, Neubauer Stefan, Rider Oliver J,
Abstract
AIMS:
We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy.
METHODS AND RESULTS:
Sixteen normal weight participants with dilated cardiomyopathy (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P 50%, P
CONCLUSIONS:
In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss.
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
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T1 Mapping and Extracellular Volume Fraction in Dilated Cardiomyopathy: A Prognosis Study.
JACC Cardiovasc Imaging2021 Sep;():. doi: S1936-878X(21)00623-9.
Li Shuang, Zhou Di, Sirajuddin Arlene, He Jian, Xu Jing, Zhuang Baiyan, Huang Jinghan, Yin Gang, Fan Xiaohan, Wu Weichun, Sun Xiaoxin, Zhao Shihua, Arai Andrew E, Lu Minjie,
Abstract
OBJECTIVES:
The aim of this study is to examine the prognostic value of T1 mapping and the extracellular volume (ECV) fraction in patients with dilated cardiomyopathy (DCM).
BACKGROUND:
Patients with DCM with functional left ventricular remodeling have poorer prognoses. Noninvasive assessment of myocardial fibrosis using T1 mapping and the ECV fraction may improve risk stratification of patients with DCM; however, this has not yet been systematically evaluated.
METHODS:
A total of 659 consecutive patients with DCM (498 men; 45 ± 15 years) who underwent cardiac magnetic resonance with T1 mapping and late gadolinium enhancement (LGE) imaging with a 1.5-T magnetic resonance scanner were enrolled in this study. Primary endpoints were cardiac-related death and heart transplantation. Secondary endpoints were hospitalization for heart failure, ventricular arrhythmias, and implantable cardioverter-defibrillator or cardiac resynchronization therapy implantation. Survival estimates were calculated by Kaplan-Meier curves with the log-rank test.
RESULTS:
During a mean follow-up of 66.3 ± 20.9 months, 122 and 205 patients with DCM reached the primary and secondary endpoints, respectively. The presence of LGE had an association with both of the primary and secondary endpoints observed in the patients with DCM (both P
CONCLUSIONS:
T1 mapping and the ECV fraction had prognostic value in patients with DCM and were particularly important in patients with DCM without LGE. Using a combination of T1 mapping, ECV fraction, and LGE provided optimal risk stratification for patients with DCM.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Predictive values of left ventricular mechanical dyssynchrony for CRT response in heart failure patients with different pathophysiology.
J Nucl Cardiol2021 Sep;():. doi: 10.1007/s12350-021-02796-3.
He Zhuo, Li Dianfu, Cui Chang, Qin Hui-Yuan, Zhao Zhongqiang, Hou Xiaofeng, Zou Jiangang, Chen Ming-Long, Wang Cheng, Zhou Weihua,
Abstract
BACKGROUND:
Cardiac resynchronization therapy (CRT) patients with different pathophysiology may influence mechanical dyssynchrony and get different ventricular resynchronization and clinical outcomes.
METHODS:
Ninety-two dilated cardiomyopathy (DCM) and fifty ischemic cardiomyopathy (ICM) patients with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included in this retrospective study. Patients were classified based on the concordance between the left ventricular (LV) lead and the latest contraction or relaxation position. If the LV lead was located on or adjacent to both the latest contraction and relaxation position, the patient was categorized into the both match group; if the LV lead was located on or adjacent to the latest contraction or relaxation position, the patient was classified into the one match group; if the LV lead was located on or adjacent to neither the latest contraction nor relaxation position, the patient was categorized to the neither group. CRT response was defined as [Formula: see text] improvement of LV ejection fraction at the 6-month follow-up. Variables with P
RESULTS:
During the follow-up period, 58.7% (54 of 92) for DCM patients and 54% (27 of 50) for ICM patients were CRT responders. The univariate analysis and stepwise multivariate analysis showed that QRS duration, systolic phase bandwidth (PBW), diastolic PBW, diastolic phase histogram standard deviation (PSD), and left ventricular mechanical dyssynchrony (LVMD) concordance were independent predictors of CRT response in DCM patients; diabetes mellitus and left ventricular end-systolic volume were significantly associated with CRT response in ICM patients. The intra-group comparison revealed that the CRT response rate was significantly different in the both match group of DCM (N = 18, 94%) and ICM (N = 24, 62%) patients (P = .016). However, there was no significant difference between DCM and ICM in the one match and neither group. For the inter-group comparison, Kruskal-Wallis H-test revealed that CRT response was significantly different in all the groups of DCM patients (P
CONCLUSIONS:
Compared with ICM patients, systolic PBW, diastolic PBW and PSD have better predictive and prognostic values for the CRT response in DCM patients. Placing the LV lead in or adjacent to the latest contraction and relaxation position can improve the clinical outcomes of DCM patients, but it does not apply to ICM patients.
© 2021. American Society of Nuclear Cardiology.
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Filamin C in cardiomyopathy: from physiological roles to DNA variants.
Heart Fail Rev2021 Sep;():. doi: 10.1007/s10741-021-10172-z.
Song Shen, Shi Anteng, Lian Hong, Hu Shengshou, Nie Yu,
Abstract
Cardiomyopathy affects approximately 1 in 500 adults and is the leading cause of death. Familial cases are common, and mutations in many genes are involved in cardiomyopathy, especially those in genes encoding cytoskeletal, sarcomere, and nuclear envelope proteins. Filamin C is an actin-binding protein encoded by filamin C (FLNC) gene and participates in sarcomere stability maintenance. FLNC was first demonstrated to be a causal gene of myofibrillar myopathy; recently, it has been found that FLNC mutation plays a critical role in the pathogenesis of cardiomyopathy. In this review, we summarized the physiological roles of filamin C in cardiomyocytes and the genetic evidence for links between FLNC mutations and cardiomyopathies. Truncated FLNC is enriched in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Non-truncated FLNC is enriched in hypertrophic cardiomyopathy and restrictive cardiomyopathy. Two major pathomechanisms in FLNC-related cardiomyopathy have been described: protein aggregation resulting from non-truncating mutations and haploinsufficiency triggered by filamin C truncation. Therefore, it is important to understand the cellular biology and molecular regulation of FLNC to design new therapies to treat patients with FLNC-related cardiomyopathy.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies.
Nat Rev Cardiol2021 Sep;():. doi: 10.1038/s41569-021-00608-2.
Walsh Roddy, Offerhaus Joost A, Tadros Rafik, Bezzina Connie R,
Abstract
Hypertrophic cardiomyopathy (HCM) was traditionally described as an autosomal dominant Mendelian disease but is now increasingly recognized as having a complex genetic aetiology. Although eight core genes encoding sarcomeric proteins account for >90% of the pathogenic variants in patients with HCM, variants in several additional genes (ACTN2, ALPK3, CSRP3, FHOD3, FLNC, JPH2, KLHL24, PLN and TRIM63), encoding non-sarcomeric proteins with diverse functions, have been shown to be disease-causing in a small number of patients. Genome-wide association studies (GWAS) have identified numerous loci in cardiomyopathy case-control studies and biobank investigations of left ventricular functional traits. Genes associated with Mendelian cardiomyopathy are enriched in the putative causal gene lists at these loci. Intriguingly, many loci are associated with both HCM and dilated cardiomyopathy but with opposite directions of effect on left ventricular traits, highlighting a genetic basis underlying the contrasting pathophysiological effects observed in each condition. This overlap extends to rare Mendelian variants with distinct variant classes in several genes associated with HCM and dilated cardiomyopathy. In this Review, we appraise the complex contribution of the non-sarcomeric, HCM-associated genes to cardiomyopathies across a range of variant classes (from common non-coding variants of individually low effect size to complete gene knockouts), which provides insights into the genetic basis of cardiomyopathies, causal genes at GWAS loci and the application of clinical genetic testing.
© 2021. Springer Nature Limited.
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Identification of CHMP4C as a new risk gene for inherited dilated cardiomyopathy.
J Genet Genomics2021 Sep;():. doi: S1673-8527(21)00298-8.
Zhou Nianwei, Tang Lu, Jiang Yingying, Li Xuejie, Shan Shifang, Yuan Bo, Qin Shengmei, Pan Cuizhen, Wang Xiaolin, Shu Xianhong, Qiu Zilong, Ge Junbo,
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Potential of Medical Management to Mitigate Suction Events in Ventricular Assist Device Patients.
ASAIO J2021 Sep;():. doi: 10.1097/MAT.0000000000001573.
Rocchi Maria, Fresiello Libera, Jacobs Steven, Dauwe Dieter, Droogne Walter, Meyns Bart,
Abstract
Ventricular suction is a common adverse event in ventricular assist device (VAD) patients and can be due to multiple underlying causes. The aim of this study is to analyze the potential of different therapeutic interventions to mitigate suction events induced by different pathophysiological conditions. To do so, a suction module was embedded in a cardiovascular hybrid (hydraulic-computational) simulator reproducing the entire cardiovascular system. An HVAD system (Medtronic) was connected between a compliant ventricular apex and a simulated aorta. Starting from a patient profile with severe dilated cardiomyopathy, four different pathophysiological conditions leading to suction were simulated: hypovolemia (blood volume: -900 ml), right ventricular failure (contractility -70%), hypotension (systemic vascular resistance: 8.3 Wood Units), and tachycardia (heart rate:185 bpm). Different therapeutic interventions such as volume infusion, ventricular contractility increase, vasoconstriction, heart rate increase, and pump speed reduction were simulated. Their effects were compared in terms of general hemodynamics and suction mitigation. Each intervention elicited a different effect on the hemodynamics for every pathophysiological condition. Pump speed reduction mitigated suction but did not ameliorate the hemodynamics. Administering volume and inducing a systemic vasoconstriction were the most efficient interventions in both improving the hemodynamics and mitigating suction. When simulating volume infusion, the cardiac powers increased, respectively, by 38%, 25%, 42%, and 43% in the case of hypovolemia, right ventricular failure, hypotension, and tachycardia. Finally, a management algorithm is proposed to identify a therapeutic intervention suited for the underlying physiologic condition causing suction.
Copyright © 2021 by the American Society for Artificial Internal Organs.
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Pheochromocytoma: An overlooked reversible cause of heart failure with reduced ejection fraction.
Turk Kardiyol Dern Ars2021 Sep;49(6):501-505. doi: 10.5543/tkda.2021.86087.
Çoner Ali, Özy?ld?z Ali Gökhan,
Abstract
Pheochromocytoma is a rare, benign tumor of adrenal medulla, and its clinical symptoms are related to catecholamine production. Clinical presentation may vary in a broad spectrum. Dilated or hypertrophied cardiomyopathies are the possible clinical outcomes of pheochromocytoma. Pheochromocytoma should be kept in mind in the differential diagnosis where resistant hypertension, palpitations, headache, and sweating accompany cardiomyopathy. Excessive adrenergic stimulation causing catecholamine discharge can trigger hypertension crisis, pulmonary edema, and myocardial necrosis. Here in this report, we aimed to present the case of a patient with pheochromocytoma related cardiomyopathy who was totally recovered after surgical excision of the tumor.
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