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1.
Nat Med ; 26(11): 1788-1800, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188278

RESUMO

Ribonucleoprotein (RNP) granules are biomolecular condensates-liquid-liquid phase-separated droplets that organize and manage messenger RNA metabolism, cell signaling, biopolymer assembly, biochemical reactions and stress granule responses to cellular adversity. Dysregulated RNP granules drive neuromuscular degenerative disease but have not previously been linked to heart failure. By exploring the molecular basis of congenital dilated cardiomyopathy (DCM) in genome-edited pigs homozygous for an RBM20 allele encoding the pathogenic R636S variant of human RNA-binding motif protein-20 (RBM20), we discovered that RNP granules accumulated abnormally in the sarcoplasm, and we confirmed this finding in myocardium and reprogrammed cardiomyocytes from patients with DCM carrying the R636S allele. Dysregulated sarcoplasmic RBM20 RNP granules displayed liquid-like material properties, docked at precisely spaced intervals along cytoskeletal elements, promoted phase partitioning of cardiac biomolecules and fused with stress granules. Our results link dysregulated RNP granules to myocardial cellular pathobiology and heart failure in gene-edited pigs and patients with DCM caused by RBM20 mutation.


Assuntos
Cardiomiopatia Dilatada/genética , Miocárdio/metabolismo , Proteínas de Ligação a RNA/genética , Ribonucleoproteínas/genética , Alelos , Animais , Cardiomiopatia Dilatada/fisiopatologia , Reprogramação Celular , Modelos Animais de Doenças , Feminino , Edição de Genes , Humanos , Masculino , Mutação/genética , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , RNA Mensageiro/genética , Retículo Sarcoplasmático/genética , Retículo Sarcoplasmático/metabolismo , Vesículas Secretórias/genética , Vesículas Secretórias/metabolismo , Suínos
2.
Mayo Clin Proc ; 95(10): 2125-2133, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33012343

RESUMO

OBJECTIVE: To investigate the association of left ventricular end-diastolic volume (LVEDV) and the response to cell therapy in patients with nonischemic dilated cardiomyopathy (NICM). PATIENTS AND METHODS: Five-year registry data from 133 consecutive patients with NICM who underwent CD34+ cell treatment were analyzed. All patients received granulocyte-colony stimulating factor; CD34+ cells were collected by apheresis and delivered by transendocardial injections. Patients with baseline LVEDV less than 200 mL (group A; n=72) and patients with LVEDV 200 to 370 mL (group B; n=54) were included. Patients with LVEDV greater than 370 mL were excluded (n=7). Favorable ejection fraction response was pre-defined by improvement in left ventricular ejection fraction (LVEF) greater than or equal to 5% at 1 y post-cell therapy. RESULTS: At baseline, groups A and B were comparable with regards to age (52±11 y in group A vs 53±10 y in group B; P=.95), sex (male: 79% vs 83%, respectively; P=.55), creatinine (1.07±0.28 mg/dL vs 1.03±0.21 mg/dL, respectively; P=.21), or N-terminal probrain natriuretic peptide (1454±1658 pg/mL vs 1589±1338 pg/mL, respectively; P=.80). Baseline LVEF was higher in group A (32.8±8.7%) than in group B (30.2±8.7%; P=.03). During follow-up, there were four deaths in group A (5.6%), and 2 in group B (3.7%, P=.63). At 1-year post-cell therapy, LVEDV decreased significantly in group B (-56±30 mL; P=.003), but not in group A (+12±97 mL; P=.13). On multivariate analysis, baseline LVEDV was an independent correlate of favorable response in LVEF to therapy (P=.02). CONCLUSION: Larger LVEDV was associated with more pronounced increase in LVEF after transendocardial CD34+ cell therapy in NICM patients, informing target individuals with the highest likelihood of regenerative response. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02445534.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Transplante de Células-Tronco , Volume Sistólico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Am J Physiol Heart Circ Physiol ; 319(3): H694-H704, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795182

RESUMO

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.


Assuntos
Insuficiência da Valva Aórtica/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Valva Mitral/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/diagnóstico por imagem , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Estudos Retrospectivos , Seul , Disfunção Ventricular Esquerda/diagnóstico por imagem
4.
Circ J ; 84(8): 1284-1293, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32624524

RESUMO

BACKGROUND: The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25-16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022). CONCLUSIONS: DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.


Assuntos
Cardiomiopatia Dilatada/genética , Hereditariedade , Linhagem , Adulto , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Progressão da Doença , Feminino , Fibrose , Predisposição Genética para Doença , Humanos , Incidência , Japão/epidemiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Fenótipo , Prevalência , Prognóstico , Estudos Prospectivos , Remodelação Ventricular
5.
Am J Physiol Heart Circ Physiol ; 319(2): H306-H319, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618513

RESUMO

Dilated cardiomyopathy (DCM) is clinically characterized by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin-filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca2+-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. We find significantly reduced fractional shortening with reduced systolic Ca2+. Contraction and Ca2+ reuptake times were slowed, which contrast with some findings in murine models of myofilament Ca2+ desensitization. We also observe increased sarcoplasmic reticulum (SR) Ca2+ load and smaller fractional SR Ca2+ release. This corresponds to a reduction in SR Ca2+-ATPase activity and increase in sodium-calcium exchanger activity. We also observe dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT), with concordant RAC-α-serine/threonine protein kinase (Akt) phosphorylation but no change to extracellular signal-regulated kinase activation in chronically paced cardiomyocytes expressing DCM mutations. These changes in Ca2+ handling and signaling are common to all three mutations, indicating an analogous pathway of disease pathogenesis in thin-filament sarcomeric DCM. Previous work has shown that changes to myofilament Ca2+ sensitivity caused by DCM mutations are qualitatively opposite from hypertrophic cardiomyopathy (HCM) mutations in the same genes. However, we find several common pathways such as increased relaxation times and NFAT activation that are also hallmarks of HCM. This suggests more complex intracellular signaling underpinning DCM, driven by the primary mutation.NEW & NOTEWORTHY Dilated cardiomyopathy (DCM) is a frequently occurring cardiac disorder with a degree of genetic inheritance. We have found that DCM mutations in proteins that regulate the contractile machinery cause alterations to contraction, calcium-handling, and some new signaling pathways that provide stimuli for disease development. We have used guinea pig cells that recapitulate human calcium-handling and introduced the mutations using adenovirus gene transduction to look at the initial triggers of disease before remodeling.


Assuntos
Sinalização do Cálcio , Cardiomiopatia Dilatada/genética , Proteínas dos Microfilamentos/genética , Mutação , Contração Miocárdica , Miócitos Cardíacos/enzimologia , Fatores de Transcrição NFATC/metabolismo , Proteína Oncogênica v-akt/metabolismo , Função Ventricular Esquerda , Animais , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/fisiopatologia , Células Cultivadas , Predisposição Genética para Doença , Cobaias , Masculino , Proteínas dos Microfilamentos/metabolismo , Fenótipo , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Tropomiosina/genética , Tropomiosina/metabolismo , Troponina I/genética , Troponina I/metabolismo , Troponina T/genética , Troponina T/metabolismo
6.
Cardiovasc Pathol ; 49: 107256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32721819

RESUMO

BACKGROUND: Heart failure is a frequently occurring complication in patients on maintenance hemodialysis (HD). However, the histological features of right ventricular endomyocardial biopsy (RVEMB) samples remain unclear. METHODS: The clinical characteristics and histological findings of consecutive patients undergoing HD with available RVEMB samples (HD group; n=28) were retrospectively compared with those of patients with dilated cardiomyopathy (n=56) and hypertensive heart disease (n=15). RESULTS: The mean myocyte diameter was significantly larger in the HD group than in the other groups (P<.001), whereas the mean percent area of fibrosis did not differ among the three groups. Immunohistochemical analysis revealed that the capillary density was significantly lower in the HD group compared with the other groups (P<.001), and it was positively associated with left ventricular ejection fraction (P=.014). The number of CD68-positive macrophages, which was significantly higher in the HD group compared with the other two groups (P<.001), was associated with cardiovascular mortality (P=.020; log-rank test). CONCLUSIONS: Myocyte hypertrophy, macrophage infiltration, and reduced capillary density were characteristic histological features of the RVEMB samples in patients undergoing HD, which may be related to the pathogenesis of cardiac dysfunction.


Assuntos
Cardiomiopatias/patologia , Cardiomiopatia Dilatada/patologia , Miocárdio/patologia , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Biópsia , Capilares/patologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Tamanho Celular , Feminino , Fibrose , Humanos , Hipertensão/complicações , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , Valor Preditivo dos Testes , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Risco
7.
Circ Heart Fail ; 13(7): e006935, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32635769

RESUMO

BACKGROUND: NEXN (nexilin) is a protein of the junctional membrane complex required for development of cardiac T-tubules. Global and cardiomyocyte-specific loss of Nexn in mice leads to a rapidly progressive dilated cardiomyopathy and premature death. Therefore, little is known as to the role of NEXN in adult cardiomyocytes. Transverse-axial tubular system remodeling are well-known features in heart failure. Although NEXN is required during development for T-tubule formation, its role, if any, in mature T-tubules remains to be addressed. METHODS: Nexn inducible adult cardiomyocyte-specific KO mice were generated. Comprehensive morphological and functional analyses were performed. Heart samples (n>3) were analyzed by molecular, biochemical, and electron microscopy analyses. Isolated single adult cardiomyocytes were analyzed by confocal microscopy, and myocyte shortening/re-lengthening and Ca2+ transient studies were conducted. RESULTS: Inducible cardiomyocyte-specific loss of Nexn in adult mice resulted in a dilated cardiomyopathy with reduced cardiac function (13% reduction in percentage fractional shortening; P<0.05). In vivo and in vitro analyses of adult mouse heart samples revealed that NEXN was essential for optimal contraction and calcium handling and was required for maintenance of T-tubule network organization (transverse tubular component in Nexn inducible adult cardiomyocyte-specific KO mice reduced by 40% with respect to controls, P<0.05). CONCLUSIONS: Results here reported reveal NEXN to be a pivotal component of adult junctional membrane complexes required for maintenance of transverse-axial tubular architecture. These results demonstrate that NEXN plays an essential role in the adult cardiomyocyte and give further understanding of pathological mechanisms responsible for cardiomyopathy in patients carrying mutations in the NEXN gene.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Proteínas dos Microfilamentos/fisiologia , Microtúbulos/fisiologia , Miócitos Cardíacos/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Fatores Etários , Animais , Cálcio/metabolismo , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microtúbulos/metabolismo , Miócitos Cardíacos/metabolismo , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/metabolismo
8.
J Clin Pathol ; 73(9): 535-543, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32616540

RESUMO

Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.


Assuntos
Apoptose/genética , Biomarcadores/análise , Cardiomiopatia Dilatada/complicações , MicroRNA Circulante/genética , Epigênese Genética , Insuficiência Cardíaca/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Ácidos Nucleicos Livres , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Medicina de Precisão
9.
Trop Doct ; 50(3): 263-266, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32487011

RESUMO

The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. A young man, suffering from idiopathic dilated cardiomyopathy with a left ventricular ejection fraction of 20%, presented with subacute, painful tender swelling in both legs initially attributed to congestive cardiac failure. No response to diuretics was achieved. Metabolically active lesions in the muscles of both lower limbs suggestive of muscle abscesses were found. A diagnosis of tropical pyomyositis was therefore made, but aspiration surprisingly revealed gram-positive yeast cells, staining of which on India ink and culture confirmed Cryptococcus. A good response to a combination of liposomal amphotericin B and flucytosine was obtained, but nevertheless the patient died from heart failure after induction of antifungal therapy.


Assuntos
Criptococose/diagnóstico , Cryptococcus/isolamento & purificação , Piomiosite/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Criptococose/tratamento farmacológico , Criptococose/patologia , Criptococose/fisiopatologia , Cryptococcus/efeitos dos fármacos , Evolução Fatal , Humanos , Masculino , Músculo Esquelético/microbiologia , Músculo Esquelético/patologia , Piomiosite/tratamento farmacológico , Piomiosite/patologia , Piomiosite/fisiopatologia
11.
Cardiovasc Diabetol ; 19(1): 84, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534593

RESUMO

BACKGROUND: Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear. METHODS: We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure. RESULTS: GLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan-Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index. CONCLUSION: Management of DCM patients with T2DM may be improved by using GLS guidance.


Assuntos
Cardiomiopatia Dilatada/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/etiologia , Insuficiência Cardíaca/etiologia , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adulto , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/mortalidade , Cardiomiopatias Diabéticas/fisiopatologia , Progressão da Doença , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
12.
Angiology ; 71(8): 726-733, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32551954

RESUMO

Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.


Assuntos
Artéria Braquial/fisiopatologia , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/fisiopatologia , Isquemia Miocárdica/complicações , Rigidez Vascular , Vasodilatação , Idoso , Artéria Braquial/diagnóstico por imagem , Cardiomiopatia Dilatada/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Prognóstico , Medição de Risco , Fatores de Risco
13.
J Cardiovasc Transl Res ; 13(3): 265-273, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32410209

RESUMO

Imaging techniques have allowed knowing the structural adaptative changes observed in the hearts of highly trained athletes. Athletes can develop very marked structural changes and the need may rise for a differential diagnosis with real cardiomyopathy. In this chapter, authors review the physiologic and morphologic features associated with athletic training and the keys to differentiate normal adaptive athlete's heart from mild or initial expression forms of left-heart side cardiomyopathies such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricle non-compaction (LVNC).


Assuntos
Atletas , Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Imagem por Ressonância Magnética , Resistência Física , Adaptação Psicológica , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Diagnóstico Diferencial , Eletrocardiografia , Humanos , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Função Ventricular Esquerda , Remodelação Ventricular
14.
J Cardiovasc Transl Res ; 13(3): 296-305, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32436168

RESUMO

Exercise training induces morphological and functional cardiovascular adaptation known as the "athlete's heart" with changes including dilatation, hypertrophy, and increased stroke volume. These changes may overlap with pathological appearances. Distinguishing athletic cardiac remodelling from cardiomyopathy is important and is a frequent medical dilemma. Cardiac magnetic resonance (CMR) has a role in clinical care as it can refine discrimination of health from a disease where ECG and echocardiography alone have left or generated uncertainty. CMR can more precisely assess cardiac structure and function as well as characterise the myocardium detecting key changes including myocardial scar and diffuse fibrosis. In this review, we will review the role of CMR in sports cardiology.


Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Atletas , Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Imagem por Ressonância Magnética , Medicina Esportiva , Adaptação Fisiológica , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Cardiologia , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/fisiopatologia , Diagnóstico Diferencial , Humanos , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Resistência Física , Valor Preditivo dos Testes , Prognóstico , Função Ventricular Esquerda , Função Ventricular Direita , Remodelação Ventricular
15.
Cell Mol Biol (Noisy-le-grand) ; 66(2): 198-203, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415948

RESUMO

This experiment aimed to study the effect of trimetazidine combined with perindopril on NT-proBNP levels in rats with dilated cardiomyopathy (DCM). 40 SD rats were selected and 10 rats were randomly selected to continue to be fed as the blank group. The other 30 rats were injected with adriamycin to establish the DCM rat model. Then they were divided into 3 groups, namely control group (without any drug intervention), trimetazidine group (with trimetazidine single-agent intervention) and combination drug group (with trimetazidine combined with perindopril intervention), with 10 DCM rats in each group. After 4 weeks of intervention, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) of rats were measured by echocardiography. The changes of plasma brain natriuretic peptide (BNP) level and n-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA. RT-PCR was used to detect the regulation of angiotensin II type 1 receptor (AT1Rs) and lamin A mRNA expression in rat myocardium. After the intervention, the LVEF%, LVEDD and LVESD measured values of the rats in the combination drug group were significantly better than those in the trimetazidine group and the control group (P< 0.05). The BNP, NT-proBNP and AT1Rs levels of the rats in the combination drug group were significantly lower than those in the trimetazidine group and the control group. The difference was statistically significant (p< 0.05). The lamin A expression of the rats in the combination drug group was significantly higher than that in the trimetazidine group and the control group. The difference was statistically significant (P< 0.05). Compared with trimetazidine single-agent, trimetazidine combined with perindopril can significantly improve the cardiac function of rats with dilated cardiomyopathy, reduce the serum NT-proBNP level and improve the expression of AT1Rs and lamin A in rats.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Perindopril/uso terapêutico , Trimetazidina/uso terapêutico , Animais , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Diástole/efeitos dos fármacos , Lamina Tipo A/metabolismo , Masculino , Perindopril/farmacologia , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Volume Sistólico/efeitos dos fármacos , Análise de Sobrevida , Sístole/efeitos dos fármacos , Trimetazidina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos
16.
Heart Vessels ; 35(10): 1439-1445, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32417957

RESUMO

The extracellular volume fraction (ECV) by T1 mapping can quantify diffuse myocardial fibrosis, and useful as a non-invasive marker for risk stratification for patients with non-ischemic dilated cardiomyopathy (NIDCM). Prolonged QRS interval on electrocardiogram is related to worse clinical outcome for heart failure patients. The purpose of this study was to evaluate the prognostic value of the combination of ECV and QRS duration for NIDCM patients. A total of 60 NIDCM patients (mean age 61 ± 12 years, mean left ventricular ejection fraction 37 ± 10%, mean QRS duration 110 ± 19 ms) were enrolled. Using a 1.5-T MR scanner and 32-channel cardiac coils, the mean ECV value of six myocardial segments at the mid-ventricular level was measured by the modified look-locker inversion recovery method. Adverse events were defined as follows: cardiac death; recurrent hospitalization due to heart failure. Patients were allocated into three groups based on ECV value and QRS duration (group 1: ECV â‰¦ 0.30 and QRS â‰¦ 120 ms; group 2: ECV > 0.30 or QRS > 120 ms; group 3: ECV > 0.30 and QRS > 120 ms). During a median follow-up duration of 370 days, 7 of 60 (12%) NIDCM patients experienced adverse events. NIDCM patients with events had longer QRS duration (134 ± 31 ms vs. 106 ± 14 ms, p = 0.01) and higher ECV (0.34 ± 0.07 vs 0.29 ± 0.05, p = 0.026) compared with those without events. On Kaplan-Meier curve analysis, significant difference was found between group 1 and group 3 (p < 0.001, log-rank test). No significant difference was found between group 1 and group 2 (p = 0.053), group 2 and group 3 (p = 0.115). The area under the receiver operating characteristic curve (AUC) for predicting adverse events was 0.778 (95% confidence interval CI 0.612-0.939) for ECV, 0.792 (95% CI 0.539-0.924) for QRS duration, 0.822 (95% CI 0.688-0.966) for combination of ECV and QRS duration. NIDCM patients with high ECV and prolonged QRS duration had significantly worse prognosis compared to those with normal ECV and normal QRS duration. The combination of ECV and QRS duration could be useful as a non-invasive method for better risk stratification for patients with NIDCM.


Assuntos
Potenciais de Ação , Cardiomiopatia Dilatada/diagnóstico , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Progressão da Doença , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Volume Sistólico , Função Ventricular Esquerda
17.
Medicine (Baltimore) ; 99(17): e19874, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332655

RESUMO

INTRODUCTION: Heart transplantation (HT) is known to be the final therapy for patients with advanced heart failure; however, the exercise capacity of these patients remains under the aged-predicted value after HT. Many studies have described the effectiveness and safety of cardiac rehabilitation (CR) in HT recipients. Nevertheless, long-term follow-up data of HT recipients undergoing CR are insufficient, and there is a lack of evidence on the long-term effects of CR. In this case report, we present the long-term benefits of CR in an HT recipient, including serial follow-up clinical data over 1 year. PATIENT CONCERNS: A 48-year-old female patient underwent HT because of advanced dilated cardiomyopathy. DIAGNOSIS: Cardiopulmonary exercise test showed reduced exercise capacity and pulmonary function. The grip power and quadriceps muscle strength were also decreased after HT. INTERVENTIONS: The patient underwent a phase I CR program for 3 months, followed by a phase III CR program for 7 months. In the beginning, moderate-intensity continuous training was conducted. Thereafter, high-intensity interval training was implemented after a period of adjustment for interval training. OUTCOMES: The exercise capacity, 6-min walk distance, muscle strength, and vital capacity were improved after CR. CONCLUSION: CR in HT recipients may improve muscle strength and pulmonary function as well as exercise capacity, without serious cardiovascular complications. Phase III CR may help maintain exercise capacity in these patients.


Assuntos
Assistência ao Convalescente/métodos , Reabilitação Cardíaca/normas , Transplante de Coração/reabilitação , Resultado do Tratamento , Reabilitação Cardíaca/métodos , Reabilitação Cardíaca/tendências , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Terapia por Exercício/métodos , Tolerância ao Exercício , Feminino , Transplante de Coração/psicologia , Transplante de Coração/normas , Humanos , Pessoa de Meia-Idade
18.
Cardiovasc J Afr ; 31(4): 180-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159583

RESUMO

BACKGROUND: Isolated left ventricular non-compaction (ILVNC), dilated cardiomyopathy (DCMO) and hypertrophic cardiomyopathy (HCM) are diseases that may be present in family members of patients with ILVNC. The primary aim of this study was to identify the prevalence and spectrum of cardiomyopathy in first-degree relatives of patients with ILVNC. A secondary aim was to compare a strategy of clinical screening, utilising only a clinical assessment and electrocardiogram (ECG), compared to one that included echocardiography for screening of family members of patients with ILVNC. METHODS: Eighty-three close relatives of 38 unrelated patients from the ILVNC clinic at the Chris Hani Baragwanath Hospital underwent a detailed clinical history, physical examination, ECG and echocardiogram. RESULTS: Echocardiographic screening revealed unexplained left ventricular (LV) dysfunction in 10 (12.05%) relatives. Nine out of the 10 individuals satisfied the criteria for diagnosis of DCMO. No cases of HCM or LVNC were identified. A strategy of clinical assessment and ECG had a sensitivity of 76% and a specificity of 42% versus the gold standard of echocardiographic screening. CONCLUSIONS: Echocardiographic screening detected DCMO in 10.8% of subjects. A strategy of clinical screening that included electrocardiography was sub-optimal as a screening strategy compared to echocardiographic screening.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia , Eletrocardiografia , Frequência Cardíaca , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Função Ventricular Esquerda , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano/genética , Cardiomiopatia Dilatada/etnologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Hipertrófica/etnologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Predisposição Genética para Doença , Frequência Cardíaca/genética , Hereditariedade , Humanos , Miocárdio Ventricular não Compactado Isolado/etnologia , Miocárdio Ventricular não Compactado Isolado/genética , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , África do Sul/epidemiologia , Função Ventricular Esquerda/genética , Adulto Jovem
19.
Radiol Med ; 125(5): 444-450, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32125636

RESUMO

OBJECTIVES: Myocardial strains can be calculated using cardiovascular magnetic resonance (CMR) feature-tracking (FT) algorithms. They show excellent intra- and inter-observer agreement but rather disappointing inter-vendor agreement. Currently, it is unknown how well CMR-FT-based strain values agree with manually obtained strain values. METHODS: In 45 subjects (15 controls, 15 acute myocardial infarction, 15 non-ischemic dilated cardiomyopathy), end-systolic manually derived strains were compared to four CMR-FT software packages. Global radial strain (GRS), global circumferential strain (GCS) and global longitudinal strain (GLS) were determined. Intra- and inter-observer agreement and agreement between manual and CMR-FT analysis were calculated. Statistical analysis included Bland-Altman plots, intra-class correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: Manual contouring yielded excellent intra-observer (ICC 0.903 (GRS) to 0.995 (GCS)) and inter-observer agreement (ICC 0.915 (GRS) to 0.966 (GCS)) with CV ranging 4.7% (GCS) to 20.7% (GRS) and 12.7% (GCS) to 20.0% (GRS), for intra-observer and inter-observer agreement, respectively. Agreement between manual and CMR-FT strain values ranged from poor to excellent, with best agreement for GCS (ICC 0.857-0.935) and intermediate for GLS (ICC 0.591-0.914), while ICC values for GRS ranged widely (ICC 0.271-0.851). In particular, two software packages showed a strong trend toward systematic underestimation of myocardial strain in radial and longitudinal direction, correlating poorly to moderately with manual contouring, i.e., GRS (ICC 0.271, CV 25.2%) and GLS (ICC 0.591, CV 17.6%). CONCLUSION: Some CMR-FT values agree poorly with manually derived strains, emphasizing to be cautious to use these software packages in the clinical setting. In particular, radial and longitudinal strain tends to be underestimated when using manually derived strains as reference.


Assuntos
Algoritmos , Cardiomiopatia Dilatada/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Software , Estresse Mecânico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Análise de Variância , Fenômenos Biomecânicos/fisiologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Infarto do Miocárdio/fisiopatologia , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia
20.
J Cardiovasc Magn Reson ; 22(1): 10, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008575

RESUMO

OBJECTIVES: The imaging features of dilated cardiomyopathy (DCM) overlap with physiological exercise-induced cardiac remodeling in active and otherwise healthy individuals. Distinguishing the two conditions is challenging. This study examined the diagnostic and prognostic roles of exercise stress imaging in asymptomatic patients with suspected DCM. METHODS: Exercise stress cardiovascular magnetic resonance (CMR) was performed in 60 asymptomatic patients with suspected DCM (dilated left ventricle and/or impaired systolic function on CMR), who also underwent DNA sequencing for DCM-causing genetic variants. Confirmed DCM was defined as genotype- and phenotype-positive (G+P+). Another 100 healthy subjects were recruited to establish normal exercise capacities (peak exercise cardiac index; PeakCI). The primary outcome was a composite of all-cause mortality, cardiac decompensation and ventricular arrhythmic events. RESULTS: No patients with confirmed G+P+ DCM had PeakCI exceeding the 35th percentile specific for age and sex. Applying this threshold in G-P+ patients, those with PeakCI below 35th percentile had characteristics similar to confirmed DCM while patients with higher PeakCI were younger, more active and higher longitudinal strain. Adverse cardiovascular events occurred only in patients with low exercise capacity (P = 0.004). CONCLUSIONS: In individuals with suspected DCM, exercise stress CMR demonstrates diagnostic and prognostic potential in distinguishing between pathological DCM and physiological exercise-induced cardiac remodeling.


Assuntos
Cardiomegalia Induzida por Exercícios , Cardiomiopatia Dilatada/diagnóstico por imagem , Teste de Esforço , Imagem Cinética por Ressonância Magnética , Adulto , Doenças Assintomáticas , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Causas de Morte , Diagnóstico Diferencial , Progressão da Doença , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Volume Sistólico , Função Ventricular Esquerda , Adulto Jovem
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