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1.
Int J Med Sci ; 21(9): 1629-1639, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006843

RESUMO

The complete molecular mechanism underlying doxorubicin-induced cardiomyopathy remains incompletely elucidated. In this investigation, we engineered mice with cardiomyocyte-specific sorting nexin 3 knockout (SNX3Cko ) to probe the potential protective effects of SNX3 ablation on doxorubicin-triggered myocardial injury, focusing on GPX4-dependent ferroptosis. Our findings indicate that SNX3 deletion normalized heart contractile/relaxation function and thwarted the escalation of cardiac injury biomarkers following doxorubicin exposure. Additionally, SNX3 deletion in the heart mitigated the inflammatory response and oxidative stress in the presence of doxorubicin. At the molecular level, the detrimental effects of doxorubicin-induced cell death, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction were alleviated by SNX3 deficiency. Molecular analysis revealed the activation of GPX4-mediated ferroptosis by doxorubicin, whereas loss of SNX3 prevented the initiation of GPX4-dependent ferroptosis. Furthermore, treatment with erastin, a ferroptosis inducer, markedly reduced cell viability, exacerbated ER stress, and induced mitochondrial dysfunction in SNX3-depleted cardiomyocytes upon doxorubicin exposure. In summary, our results demonstrate that SNX3 deficiency shielded the heart from doxorubicin-induced myocardial dysfunction by modulating GPX4-associated ferroptosis.


Assuntos
Cardiomiopatias , Doxorrubicina , Ferroptose , Camundongos Knockout , Miócitos Cardíacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Nexinas de Classificação , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Animais , Doxorrubicina/efeitos adversos , Doxorrubicina/toxicidade , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiomiopatias/genética , Nexinas de Classificação/genética , Nexinas de Classificação/metabolismo , Camundongos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos
2.
Sci Rep ; 14(1): 15141, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956129

RESUMO

Pediatric cardiomyopathies are mostly attributed to variants in sarcomere-related genes. Unfortunately, the genetic architecture of pediatric cardiomyopathies has never been previously studied in Jordan. We sought to uncover the genetic landscape of 14 patients from nine families with several subtypes of pediatric cardiomyopathies in Jordan using Exome sequencing (ES). Our investigation identified pathogenic and likely pathogenic variants in seven out of nine families (77.8%), clustering in sarcomere-related genes. Surprisingly, phenocopies of sarcomere-related hypertrophic cardiomyopathies were evident in probands with glycogen storage disorder and mitochondrial-related disease. Our study underscored the significance of streamlining ES or expanding cardiomyopathy-related gene panels to identify plausible phenocopies of sarcomere-related cardiomyopathies. Our findings also pointed out the need for genetic testing in patients with cardiomyopathy and their at-risk family members. This can potentially lead to better management strategies, enabling early interventions, and ultimately enhancing their prognosis. Finally, our findings provide an initial contribution to the currently absent knowledge about the molecular underpinnings of cardiomyopathies in Jordan.


Assuntos
Cardiomiopatias , Linhagem , Sarcômeros , Humanos , Jordânia , Masculino , Feminino , Sarcômeros/genética , Criança , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico , Pré-Escolar , Sequenciamento do Exoma , Lactente , Fenótipo , Adolescente , Mutação , Testes Genéticos/métodos
3.
Turk Kardiyol Dern Ars ; 52(5): 357-361, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982822

RESUMO

Right ventricular pacing (RVP) is conventionally preferred in the treatment of patients with atrioventricular block. However, long-term RVP may lead to pacing-induced cardiomyopathy (PICM), characterized by new-onset or worsening ventricular functions due to dyssynchronous ventricular electrical activation, abnormal ventricular remodeling, and increased energy expenditure. Historically, biventricular pacing (BVP) and guideline-directed medical therapy were the only treatment option for PICM. Recently, conduction system pacing, including left bundle branch area pacing (LBBaP), has emerged as a physiological alternative to BVP, showing better results in electro-mechanical ventricular synchronization and hemodynamic parameters compared to BVP. We present a case involving a patient from whom the PICM was successfully recovered shortly after LBBaP.


Assuntos
Estimulação Cardíaca Artificial , Cardiomiopatias , Humanos , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Estimulação Cardíaca Artificial/métodos , Estimulação Cardíaca Artificial/efeitos adversos , Eletrocardiografia , Masculino , Ventrículos do Coração/fisiopatologia
4.
Nutrients ; 16(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38999835

RESUMO

Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.


Assuntos
Dieta Hiperlipídica , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Modelos Animais de Doenças , Miocárdio/patologia , Miocárdio/metabolismo , Fibrose , Masculino , Remodelação Ventricular , Desmogleína 2/genética , Miocardite/etiologia , Miocardite/fisiopatologia , Camundongos Endogâmicos C57BL , Displasia Arritmogênica Ventricular Direita/etiologia , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Adiponectina/sangue , Inflamação , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia
5.
BMC Cardiovasc Disord ; 24(1): 339, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965461

RESUMO

BACKGROUND: Zolpidem is a non-benzodiazepine hypnotic widely used to manage insomnia. Zolpidem-triggered atrial fibrillation (AF) in patients with cardiomyopathy has never been reported before. CASE PRESENTATION: A 40-year-old man with Duchenne muscular dystrophy-related cardiomyopathy attempted suicide and developed new-onset AF after zolpidem overdose. One year before admission, the patient visited our clinic due to chest discomfort and fatigue after daily walks for 1 month; both electrocardiography (ECG) and 24-hour Holter ECG results did not detect AF. After administration of cardiac medication (digoxin 0.125 mg/day, spironolactone 40 mg/day, furosemide 20 mg/day, bisoprolol 5 mg/day, sacubitril/valsartan 12/13 mg/day), he felt better. AF had never been observed before this admission via continuous monitoring during follow-up. Sixteen days before admission, the patient saw a sleep specialist and started zolpidem tartrate tablets (10 mg/day) due to insomnia for 6 months; ECG results revealed no significant change. The night before admission, the patient attempted suicide by overdosing on 40 mg of zolpidem after an argument, which resulted in severe lethargy. Upon admission, his ECG revealed new-onset AF, necessitating immediate cessation of zolpidem. Nine hours into admission, AF spontaneously terminated into normal sinus rhythm. Results from the ECG on the following days and the 24-hour Holter ECG at 1-month follow-up showed that AF was not detected. CONCLUSIONS: This study provides valuable clinical evidence indicating that zolpidem overdose may induce AF in patients with cardiomyopathy. It serves as a critical warning for clinicians when prescribing zolpidem, particularly for patients with existing heart conditions. Further large-scale studies are needed to validate this finding and to explore the mechanisms between zolpidem and AF.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Zolpidem , Humanos , Zolpidem/efeitos adversos , Masculino , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/induzido quimicamente , Adulto , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/fisiopatologia , Cardiomiopatias/diagnóstico , Tentativa de Suicídio , Overdose de Drogas/diagnóstico , Frequência Cardíaca/efeitos dos fármacos , Piridinas/efeitos adversos
6.
Clin Cardiol ; 47(7): e24307, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953367

RESUMO

BACKGROUND: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). RESULTS: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post-CABG was reduced in patients with versus without viability (random-effects model: odds ratio: 0.42; 95% confidence interval: 0.29-0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. CONCLUSION: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount.


Assuntos
Ponte de Artéria Coronária , Isquemia Miocárdica , Função Ventricular Esquerda , Humanos , Cardiomiopatias/fisiopatologia , Cardiomiopatias/cirurgia , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/complicações , Ecocardiografia sob Estresse/métodos , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/cirurgia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/complicações , Miocárdio/patologia , Sobrevivência de Tecidos , Tomografia Computadorizada de Emissão de Fóton Único , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologia
7.
J Pregnancy ; 2024: 7713590, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957710

RESUMO

Preeclampsia and peripartum cardiomyopathy (PPCM) are significant obstetric problems that can arise during or after pregnancy. Both are known to be causes of maternal mortality and morbidity. Several recent studies have suggested a link between preeclampsia and the pathophysiology of PPCM. However, the common thread that connects the two has yet to be thoroughly and fully articulated. Here, we investigate the complex dynamics of preeclampsia and PPCM in this review. Our analysis focuses mainly on inflammatory and immunological responses, endothelial dysfunction as a shared pathway, and potential genetic predisposition to both diseases. To begin, we will look at how excessive inflammatory and immunological responses can lead to clinical symptoms of both illnesses, emphasizing the role of proinflammatory cytokines and immune cells in modifying vascular and tissue responses. Second, we consider endothelial dysfunction to be a crucial point at which endothelial damage and activation contribute to pathogenesis through increased vascular permeability, vascular dysfunction, and thrombus formation. Finally, we examine recent information suggesting genetic predispositions to preeclampsia and PPCM, such as genetic variants in genes involved in the management of blood pressure, the inflammatory response, and heart structural integrity. With this synergistic study, we seek to encourage more research and creative therapy solutions by emphasizing the need for an interdisciplinary approach to understanding and managing the connection between preeclampsia and PPCM.


Assuntos
Cardiomiopatias , Período Periparto , Pré-Eclâmpsia , Humanos , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/genética , Gravidez , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Predisposição Genética para Doença , Endotélio Vascular/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/genética
8.
Orphanet J Rare Dis ; 19(1): 248, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961493

RESUMO

BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05). CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.


Assuntos
Carnitina , Hiperamonemia , Membro 5 da Família 22 de Carreadores de Soluto , Humanos , China/epidemiologia , Carnitina/deficiência , Recém-Nascido , Membro 5 da Família 22 de Carreadores de Soluto/genética , Hiperamonemia/genética , Hiperamonemia/epidemiologia , Hiperamonemia/diagnóstico , Cardiomiopatias/genética , Cardiomiopatias/epidemiologia , Doenças Musculares/genética , Doenças Musculares/epidemiologia , Mutação/genética , Triagem Neonatal/métodos , População do Leste Asiático
10.
J Comp Eff Res ; 13(7): e230158, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38869839

RESUMO

Aim: The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.


Assuntos
Cardiomiopatias , Teste de Caminhada , Humanos , Teste de Caminhada/métodos , Cardiomiopatias/fisiopatologia , Cardiomiopatias/diagnóstico , Hospitalização/estatística & dados numéricos , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/fisiopatologia , Ensaios Clínicos como Assunto/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico
11.
Sci Rep ; 14(1): 14114, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898142

RESUMO

The aim of this study was to develop a simple but effective nomogram to predict risk of septic cardiomyopathy (SCM) in the intensive care unit (ICU). We analyzed data from patients who were first admitted to the ICU for sepsis between 2008 and 2019 in the MIMIC-IV database, with no history of heart disease, and divided them into a training cohort and an internal validation cohort at a 7:3 ratio. SCM is defined as sepsis diagnosed in the absence of other cardiac diseases, with echocardiographic evidence of left (or right) ventricular systolic or diastolic dysfunction and a left ventricular ejection fraction (LVEF) of less than 50%. Variables were selected from the training cohort using the Least Absolute Shrinkage and Selection Operator (LASSO) regression to develop an early predictive model for septic cardiomyopathy. A nomogram was constructed using logistic regression analysis and its receiver operating characteristic (ROC) and calibration were evaluated in two cohorts. A total of 1562 patients participated in this study, with 1094 in the training cohort and 468 in the internal validation cohort. SCM occurred in 13.4% (147 individuals) in the training cohort, 16.0% (75 individuals) in the internal validation cohort. After adjusting for various confounding factors, we constructed a nomogram that includes SAPS II, Troponin T, CK-MB index, white blood cell count, and presence of atrial fibrillation. The area under the curve (AUC) for the training cohort was 0.804 (95% CI 0.764-0.844), and the Hosmer-Lemeshow test showed good calibration of the nomogram (P = 0.288). Our nomogram also exhibited good discriminative ability and calibration in the internal validation cohort. Our nomogram demonstrated good potential in identifying patients at increased risk of SCM in the ICU.


Assuntos
Cardiomiopatias , Unidades de Terapia Intensiva , Nomogramas , Sepse , Humanos , Masculino , Feminino , Cardiomiopatias/diagnóstico , Pessoa de Meia-Idade , Sepse/diagnóstico , Idoso , Curva ROC , Fatores de Risco , Medição de Risco/métodos
12.
Cells ; 13(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38891055

RESUMO

Intracellular cargo delivery via distinct transport routes relies on vesicle carriers. A key trafficking route distributes cargo taken up by clathrin-mediated endocytosis (CME) via early endosomes. The highly dynamic nature of the endosome network presents a challenge for its quantitative analysis, and theoretical modelling approaches can assist in elucidating the organization of the endosome trafficking system. Here, we introduce a new computational modelling approach for assessment of endosome distributions. We employed a model of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with inherited mutations causing dilated cardiomyopathy (DCM). In this model, vesicle distribution is defective due to impaired CME-dependent signaling, resulting in plasma membrane-localized early endosomes. We recapitulated this in iPSC-CMs carrying two different mutations, TPM1-L185F and TnT-R141W (MUT), using 3D confocal imaging as well as super-resolution STED microscopy. We computed scaled distance distributions of EEA1-positive vesicles based on a spherical approximation of the cell. Employing this approach, 3D spherical modelling identified a bi-modal segregation of early endosome populations in MUT iPSC-CMs, compared to WT controls. Moreover, spherical modelling confirmed reversion of the bi-modal vesicle localization in RhoA II-treated MUT iPSC-CMs. This reflects restored, homogeneous distribution of early endosomes within MUT iPSC-CMs following rescue of CME-dependent signaling via RhoA II-dependent RhoA activation. Overall, our approach enables assessment of early endosome distribution in cell-based disease models. This new method may provide further insight into the dynamics of endosome networks in different physiological scenarios.


Assuntos
Endossomos , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Endossomos/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Endocitose , Mutação/genética , Simulação por Computador , Proteína rhoA de Ligação ao GTP/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Imageamento Tridimensional , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Modelos Biológicos , Tropomiosina/metabolismo , Tropomiosina/genética
13.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892040

RESUMO

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.


Assuntos
Cardiomiopatias , Cirrose Hepática , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Animais , Antagonistas Adrenérgicos beta/uso terapêutico , Antioxidantes/uso terapêutico
14.
Sci Rep ; 14(1): 14889, 2024 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937555

RESUMO

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71-0.96), a sensitivity of 0.98 (95% CI 0.75-1.00) and a specificity of 0.73 (95% CI 0.58-0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65-0.94), ECG branch: 0.54 (95% CI 0.26-0.82), Clinical branch: 0.64 (95% CI 0.39-0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation.


Assuntos
Arritmias Cardíacas , Cardiomiopatias , Desfibriladores Implantáveis , Eletrocardiografia , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cardiomiopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Idoso , Inteligência Artificial , Aprendizado Profundo , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Medição de Risco/métodos , Fatores de Risco , Curva ROC
15.
Rev Fac Cien Med Univ Nac Cordoba ; 81(2): 432-452, 2024 06 28.
Artigo em Espanhol | MEDLINE | ID: mdl-38941220

RESUMO

The diagnosis of Cirrhotic Cardiomyopathy is based on severe hepatic cirrosis with deterioration of cardiac function without previous cardiopathy, but this is subclinical during a long time. In this second part we review the non-invasive diagnostic methods and their prognostic value in patients with or without hepatic transplant, from ECG to cardiac images of magnetic resonance.


El diagnóstico de Cardiomiopatía Cirrótica está basado en la presencia de cirrosis hepática avanzada con alteraciones de la función cardíaca sin cardiopatía pre-existente, pero en gran parte de su evolución natural ésta es subclínica. Por ello son imprescindibles los estudios complementarios no invasivos para confirmar el diagnóstico y su rol pronóstico en pacientes con o sin trasplante hepático. En esta segunda parte revisamos los métodos de diagnóstico desde el ECG hasta las imágenes de resonancia magnética cardíaca.


Assuntos
Cardiomiopatias , Cirrose Hepática , Imageamento por Ressonância Magnética , Humanos , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Cirrose Hepática/complicações , Eletrocardiografia , Prognóstico
16.
Int J Mol Sci ; 25(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38928407

RESUMO

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area.


Assuntos
Fibrose , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Endotélio Vascular/efeitos da radiação , Endotélio Vascular/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/sangue , Miocárdio/patologia , Miocárdio/metabolismo , Radioterapia/efeitos adversos , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Colesterol/sangue , Biomarcadores/sangue
17.
Genes (Basel) ; 15(6)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927710

RESUMO

Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic cause. Next-Generation Sequencing (NGS) has expanded the genes studied for CMs; however, the yield is still around 50%. The systematic study of Copy Number Variants (CNVs) could contribute to improving our diagnostic capacity. These alterations have already been described as responsible for cardiomyopathies in some cases; however, their impact has been rarely assessed. We analyzed the clinical significance of CNVs in cardiomyopathies by studying 11,647 affected patients, many more than those considered in previously published studies. We evaluated the yield of the systematic study of CNVs in a production context using NGS and a novel CNV detection software tool v2.0 that has demonstrated great efficacy, maximizing sensitivity and avoiding false positives. We obtained a CNV analysis yield of 0.8% that fluctuated depending on the type of cardiomyopathy studied (0.29% HCM, 1.41% DCM, 1.88% ARVC, 1.8% LVNC, 1.45% RCM), and we present the frequency of occurrence for 18 genes that agglutinate the 95 pathogenic/likely pathogenic CNVs detected. We conclude the importance of including in diagnostic tests a systematic study of these genetic alterations for the different cardiomyopathies.


Assuntos
Cardiomiopatias , Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Variações do Número de Cópias de DNA/genética , Cardiomiopatias/genética , Masculino , Feminino , Adulto , Relevância Clínica
18.
Europace ; 26(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38934242

RESUMO

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. METHODS AND RESULTS: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. CONCLUSION: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.


Assuntos
Neuropatias Amiloides Familiares , Fibrilação Atrial , Flutter Atrial , Cardiomiopatias , Ablação por Cateter , Humanos , Ablação por Cateter/efeitos adversos , Masculino , Flutter Atrial/cirurgia , Flutter Atrial/etiologia , Feminino , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Idoso , Neuropatias Amiloides Familiares/cirurgia , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/mortalidade , Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Resultado do Tratamento , Pessoa de Meia-Idade , Recidiva , Taquicardia Supraventricular/cirurgia , Taquicardia Supraventricular/etiologia , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/diagnóstico , Estudos Retrospectivos , Pré-Albumina/genética , Pré-Albumina/metabolismo
19.
Clin Cardiol ; 47(6): e24298, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873847

RESUMO

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.


Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Taxa de Filtração Glomerular , Humanos , Masculino , Feminino , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/fisiopatologia , Idoso , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Cardiomiopatias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Seguimentos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Progressão da Doença , Rim/fisiopatologia , Fatores de Tempo , Incidência , Medição de Risco/métodos
20.
J Am Heart Assoc ; 13(13): e034055, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38904229

RESUMO

BACKGROUND: Although peripartum cardiomyopathy (PPCM) is a fatal disease affecting young patients and fetuses, little is known about its recent prognosis and risk factors. This study investigated temporal trends in clinical characteristics and outcomes for PPCM in a nationwide multicenter registry. METHODS AND RESULTS: The study population comprised 340 patients (mean age, 33 years) who were diagnosed with PPCM between January 2000 and September 2022 in 26 tertiary hospitals in South Korea. PPCM was defined as heart failure with left ventricular ejection fraction ≤45% and no previously known cardiac disease. The main study outcomes included time to the first occurrence of all-cause death, heart transplantation, and cardiovascular hospitalization. The diagnosis of PPCM cases increased notably during the study period (P<0.001). However, clinical outcomes showed no significant improvement (all-cause death for 10 years: 0.9% [2000-2010] versus 2.3% [2011-2022], P=0.450; all-cause death and heart transplantation for 10 years: 3.6% [2000-2010] versus 3.0% [2011-2022] P=0.520; all-cause death, heart transplantation, and cardiovascular hospitalization for 10 years: 11.7% [2000-2010] versus 19.8% [2011-2022], P=0.240). High body mass index (hazard ratio [HR], 1.106 [95% CI, 1.024-1.196]; P=0.011), the presence of gestational diabetes (HR, 5.346 [95% CI, 1.778-16.07]; P=0.002), and increased baseline left ventricular end-diastolic dimension (HR, 1.078 [95% CI, 1.002-1.159]; P=0.044) were significant risk factors for poor prognosis. CONCLUSIONS: While the incidence of PPCM has increased over the past 20 years, the prognosis has not improved significantly. Timely management and close follow-up are necessary for high-risk patients with PPCM with high body mass index, gestational diabetes, or large left ventricular end-diastolic dimension.


Assuntos
Cardiomiopatias , Período Periparto , Complicações Cardiovasculares na Gravidez , Sistema de Registros , Humanos , Feminino , Adulto , Gravidez , República da Coreia/epidemiologia , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/mortalidade , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/terapia , Fatores de Risco , Fatores de Tempo , Transplante de Coração/tendências , Transplante de Coração/estatística & dados numéricos , Prognóstico , Função Ventricular Esquerda , Volume Sistólico , Causas de Morte/tendências , Hospitalização/tendências , Hospitalização/estatística & dados numéricos , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/terapia , Transtornos Puerperais/mortalidade , Transtornos Puerperais/fisiopatologia , Estudos Retrospectivos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Incidência
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