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1.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808720

RESUMO

Using a murine model of chronic ischemic cardiomyopathy caused by an old myocardial infarction (MI), we have previously found that three doses of 1 × 106 c-kit positive cardiac cells (CPCs) are more effective than a single dose of 1 × 106 cells. The goal of this study was to determine whether the beneficial effects of three doses of CPCs (1 × 106 cells each) can be fully replicated by a single combined dose of 3 × 106 CPCs. Mice underwent a 60-min coronary occlusion; after 90 days of reperfusion, they received three echo-guided intraventricular infusions at 5-week intervals: (1) vehicle × 3; (2) one combined dose of CPCs (3 × 106) and vehicle × 2; or (3) three doses of CPCs (1 × 106 each). In the combined-dose group, left ventricular ejection fraction (LVEF) improved after the 1st CPC infusion, but not after the 2nd and 3rd (vehicle) infusions. In contrast, in the multiple-dose group, LVEF increased after each CPC infusion; at the final echo, LVEF averaged 35.2 ± 0.6% (p < 0.001 vs. the vehicle group, 27.3 ± 0.2%). At the end of the study, the total cumulative change in EF from pretreatment values was numerically greater in the multiple-dose group (6.6 ± 0.6%) than in the combined-dose group (4.8 ± 0.8%), although the difference was not statistically significant (p = 0.08). Hemodynamic studies showed that several parameters of LV function in the multiple-dose group were numerically greater than in the combined-dose group (p = 0.08 for the difference in LVEF). Compared with vehicle, cardiomyocyte cross-sectional area was reduced only in the multiple-dose group (-32.7%, 182.6 ± 15.1 µm2 vs. 271.5 ± 27.2 µm2, p < 0.05, in the risk region and -28.5%, 148.5 ± 12.1 µm2 vs. 207.6 ± 20.5 µm2, p < 0.05, in the noninfarcted region). LV weight/body weight ratio and LV weight/tibia length ratios were significantly reduced in both cell treated groups vs. the vehicle group, indicating the attenuation of LV hypertrophy; however, the lung weight/body weight ratio was significantly reduced only in the multiple-dose group, suggesting decreased pulmonary congestion. Taken together, these results indicate that in mice with chronic ischemic cardiomyopathy, the beneficial effects of three doses of CPCs on LV function and hypertrophy cannot be fully replicated with a single dose, notwithstanding the fact that the total number of cells delivered with one or three doses is the same. Thus, it is the multiplicity of doses, and not the total number of cells, that accounts for the superiority of the repeated-dose paradigm. This study supports the idea that the efficacy of cell therapy in heart failure can be augmented by repeated administrations.


Assuntos
Cardiomiopatias/etiologia , Dosagem de Genes , Isquemia Miocárdica/complicações , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Animais , Biomarcadores , Biópsia , Pesos e Medidas Corporais , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Cardiomiopatias/terapia , Células Cultivadas , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Testes de Função Cardíaca , Hemodinâmica , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Camundongos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Isquemia Miocárdica/etiologia , Proteínas Proto-Oncogênicas c-kit/metabolismo
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 174-179, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627214

RESUMO

OBJECTIVE: To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage. METHODS: A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed. RESULTS: Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (P < 0.05). Among the children with primary hypertension, 20 (36%) had left ventricular hypertrophy. The hypertension group had significantly larger left atrial diameter and aortic root diameter than the control group (P < 0.05). The hypertension group had a significantly higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity than the control group (P < 0.05). The correlation analysis showed that in children with primary hypertension, serum uric acid was positively correlated with LVM (r=0.534, P < 0.01), left atrial diameter (r=0.459, P < 0.01), and aortic root diameter (r=0.361, P=0.010). After adjustment for blood pressure, serum uric acid was still positively correlated with the above parameters (P < 0.05). CONCLUSIONS: Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.


Assuntos
Hipertensão , Ácido Úrico , Pressão Sanguínea , Criança , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Estudos Retrospectivos
3.
Life Sci ; 268: 118936, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421523

RESUMO

AIMS: During oxidative stress mitochondria become the main source of endogenous reactive oxygen species (ROS) production. In the present study, we aimed to clarify the effects of pharmacological PARP-1 inhibition on mitochondrial function and quality control processes. MAIN METHODS: L-2286, a quinazoline-derivative PARP inhibitor, protects against cardiovascular remodeling and heart failure by favorable modulation of signaling routes. We examined the effects of PARP-1 inhibition on mitochondrial quality control processes and function in vivo and in vitro. Spontaneously hypertensive rats (SHRs) were treated with L-2286 or placebo. In the in vitro model, 150 µM H2O2 stress was applied on neonatal rat cardiomyocytes (NRCM). KEY FINDINGS: PARP-inhibition prevented the development of left ventricular hypertrophy in SHRs. The interfibrillar mitochondrial network were less fragmented, the average mitochondrial size was bigger and showed higher cristae density compared to untreated SHRs. Dynamin related protein 1 (Drp1) translocation and therefore the fission of mitochondria was inhibited by L-2286 treatment. Moreover, L-2286 treatment increased the amount of fusion proteins (Opa1, Mfn2), thus preserving structural stability. PARP-inhibition also preserved the mitochondrial genome integrity. In addition, the mitochondrial biogenesis was also enhanced due to L-2286 treatment, leading to an overall increase in the ATP production and improvement in survival of stressed cells. SIGNIFICANCE: Our results suggest that the modulation of mitochondrial dynamics and biogenesis can be a promising therapeutical target in hypertension-induced myocardial remodeling and heart failure.


Assuntos
Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Animais , Células Cultivadas , Citrato (si)-Sintase/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Eletrocardiografia , Glutationa/metabolismo , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/ultraestrutura , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/patologia , Peptídeo Natriurético Encefálico/sangue , Piperidinas/farmacologia , Quinazolinas/farmacologia , Ratos Endogâmicos SHR , Ratos Wistar
4.
Biomed Pharmacother ; 133: 110989, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378994

RESUMO

BACKGROUND: Maternal obesity induces adverse cardiac programming in offspring, and effective interventions are needed to prevent cardiovascular ill-health. Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity in mice results in left ventricular remodelling and hypertrophy in early childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these effects in a sex-dependent manner. METHODS AND RESULTS: The maternal obesity was induced in mice by the consumption of a Western diet accompanied by a 20 % sucrose solution. To determine the effect of NAC on the cardiac outcomes induced by maternal obesity, obese dams were continuously exposed to the obesogenic diet, with or without the oral NAC treatment during pregnancy. Left ventricular remodelling and hypertrophy occurred as early as 7 days after birth in the male offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression of key genes and markers related to cardiac fibrosis accompanied by more disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. When we next evaluated the level of oxidative stress in the hearts of neonatal mice, the activity of enzymatic antioxidants declined and expression of NOX enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate increased heart weight, interventricular septal thickness, and collagen content in male O-OB/NAC pups. CONCLUSIONS: Collectively, our results indicated that NAC blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal offspring in the setting of maternal obesity, potentially acting by reducing oxidative stress. The present study provides a basis for investigating the role of NAC in nutrition-related cardiac programming.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/prevenção & controle , Obesidade Materna/complicações , Estresse Oxidativo/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Fibrose , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Camundongos Endogâmicos C57BL , Obesidade Materna/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores Sexuais
5.
Int Heart J ; 61(5): 961-969, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921672

RESUMO

Left ventricular (LV) remodeling with aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after transcatheter aortic valve implantation (TAVI) has not been elucidated in a Japanese population. This study aims to determine whether any sex-related differences in LV or reverse remodeling after TAVI exist in the context of severe AS.Of 208 patients who received TAVI for severe AS in our institution, 100 (men, 42; mean age, 83.0 ± 4.9 years) underwent transthoracic echocardiography before and 3 months after TAVI. Despite similar valvular gradients, women with severe AS had lower indexed LV mass (LVMi) than did men (152.3 ± 35.4 versus 173.2 ± 44.6 g/m2, P = 0.005), with smaller indexed LV end-diastolic (LVEDVi) (50.2 ± 13.3 versus 61.4 ± 20.7 mL/m2, P = 0.001) and end-systolic (LVESVi; 17.9 ± 8.7 versus 24.3 ± 13.8 mL/m2, P = 0.006) volumes. After TAVI, women (-6.0% ± 14.4%) had higher reduction in the rate of change of relative wall thickness (RWT) than did men (4.4% ± 19.0%, P = 0.003). Men (-8.9% ± 3.9%) had higher reduction in the rate of change of LVEDVi than did women (1.5% ± 3.3%, P = 0.045). Incidence of LV reverse remodeling defined as a reduction in LVESV of >15% was significantly higher in men (50%) than in women (26%, P = 0.013).In addition to sex differences in the pattern of LV remodeling with AS, reverse LV remodeling after TAVI also differed between sexes.


Assuntos
Estenose da Valva Aórtica/cirurgia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Remodelação Ventricular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Japão , Masculino , Índice de Gravidade de Doença , Fatores Sexuais , Substituição da Valva Aórtica Transcateter , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(39): e22326, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991443

RESUMO

RATIONALE: The most common cardiac involvement of Fabry disease (FD) is left ventricular hypertrophy (LVH), which usually occurs in male patients over the age of 30. In rare cases, it can progress to ventricular dilation in the late stage of the disease. PATIENT CONCERNS: A 16-year-old boy presenting with recurrent extremity pain and chest distress was admitted to our hospital. Imaging examinations revealed ventricular dilation. DIAGNOSIS: α-Galactosidase A enzyme assay and GLA gene sequencing confirmed the diagnosis of FD and revealed a novel mutation c.76_77insT. INTERVENTIONS: The patient was treated using metoprolol (23.75 mg qd) and angiotensin-converting enzyme inhibitor (fosinopril sodium 5 mg qd). He refused enzyme replacement therapy for financial reasons. OUTCOMES: The echocardiography, electrocardiography, renal function, and routine blood and urine tests performed 20 months after the patients discharge from hospital showed no significant changes. The patient reported a slow and gradual decrease in the frequency and degree of pain and chest distress, starting approximately 24 months after discharge. LESSONS: Cardiac involvement of FD can progress rapidly in some cases. Screening for FD should be considered in patients with unexplained ventricular dilation, especially in those with a history of typical FD manifestations.


Assuntos
Dilatação Patológica/diagnóstico por imagem , Doença de Fabry/complicações , Doença de Fabry/genética , Hipertrofia Ventricular Esquerda/etiologia , alfa-Galactosidase/genética , Adolescente , Assistência ao Convalescente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ecocardiografia/métodos , Eletrocardiografia/métodos , Terapia de Reposição de Enzimas/economia , Doença de Fabry/tratamento farmacológico , Fosinopril/uso terapêutico , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Metoprolol/uso terapêutico , Mutação , Simpatolíticos/uso terapêutico , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(37): e22119, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925759

RESUMO

The presence of left ventricular hypertrophy has been confirmed to be an independent risk factor for stroke and death in patients with atrial fibrillation. This retrospective study aimed to evaluate the potential risk factors for left ventricular hypertrophy in patients with atrial fibrillation.A series of consecutive patients diagnosed with atrial fibrillation between June 2018 and December 2019 were included. The patients' clinical data were analyzed. The cut-off values, sensitivity and specificity of the independent risk factors were calculated using a receiver operating characteristic curve.Among 87 patients with atrial fibrillation, 39 patients with left ventricular hypertrophy and 48 patients without left ventricular hypertrophy were included. Multivariate logistic regression analysis showed that red blood cell distribution width (odds ratio [OR] 4.89, 95% confidence interval [CI]: 1.69-14.13, P < .05) was an independent risk factor, while the concentration of low-density lipoprotein (OR 0.37, 95% CI: 0.17-0.83, P < .05) and left ventricular ejection fraction (OR 0.88, 95% CI: 0.82-0.95, P < .05) were inversely associated with left ventricular hypertrophy in atrial fibrillation patients. The receiver operating characteristic curve demonstrated that the area under the curve was 0.80 (95% CI: 0.71-0.90, P < .05) with a cut-off value of 13.05, and the red blood cell distribution width predicted left ventricular hypertrophy status among atrial fibrillation patients with a sensitivity of 72.1% and a specificity of 76.9%.Red blood cell distribution width was associated with left ventricular hypertrophy in patients with atrial fibrillation.


Assuntos
Fibrilação Atrial/sangue , Índices de Eritrócitos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico , Idoso , Fibrilação Atrial/complicações , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco
8.
J Cardiovasc Magn Reson ; 22(1): 57, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32758255

RESUMO

BACKGROUND: Myocardial fibrosis is observed in multiple cardiac conditions including hypertension and aortic stenosis. Excessive fibrosis is associated with adverse clinical outcomes, but longitudinal human data regarding changes in left ventricular remodelling and fibrosis over time are sparse because of the slow progression, thereby making longitudinal studies challenging. The purpose of this study was to establish and characterize a mouse model to study the development and regression of left ventricular hypertrophy and myocardial fibrosis in response to increased blood pressure and to understand how these processes reverse remodel following normalisation of blood pressure. METHODS: We performed a longitudinal study with serial cardiovascular magnetic resonance (CMR) imaging every 2 weeks in mice (n = 31) subjected to angiotensin II-induced hypertension for 6 weeks and investigated reverse remodelling following normalisation of afterload beyond 6 weeks (n = 9). Left ventricular (LV) volumes, mass, and function as well as myocardial fibrosis were measured using cine CMR and the extracellular volume fraction (ECV) s. RESULTS: Increased blood pressure (65 ± 12 vs 85 ± 9 mmHg; p < 0.001) resulted in higher indices of LV hypertrophy (0.09 [0.08, 0.10] vs 0.12 [0.11, 0.14] g; p < 0.001) and myocardial fibrosis (ECV: 0.24 ± 0.03 vs 0.30 ± 0.02; p < 0.001) whilst LV ejection fraction fell (LVEF, 59.3 [57.6, 59.9] vs 46.9 [38.5, 49.6] %; p < 0.001). We found a strong correlation between ECV and histological myocardial fibrosis (r = 0.89, p < 0.001). Following cessation of angiotensin II and normalisation of blood pressure (69 ± 5 vs baseline 65 ± 12 mmHg; p = 0.42), LV mass (0.11 [0.10, 0.12] vs 0.09 [0.08, 0.11] g), ECV (0.30 ± 0.02 vs 0.27 ± 0.02) and LVEF (51.1 [42.9, 52.8] vs 59.3 [57.6, 59.9] %) improved but remained impaired compared to baseline (p < 0.05 for all). There was a strong inverse correlation between LVEF and %ECV during both systemic hypertension (r = - 0.88, p < 0.001) and the increases in ECV observed in the first two weeks of increased blood pressure predicted the reduction in LVEF after 6 weeks (r = - 0.77, p < 0.001). CONCLUSIONS: We have established and characterized angiotensin II infusion and repeated CMR imaging as a model of LV hypertrophy and reverse remodelling in response to systemic hypertension. Changes in myocardial fibrosis and alterations in cardiac function are only partially reversible following relief of hypertension.


Assuntos
Pressão Sanguínea , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Miocárdio/patologia , Função Ventricular Esquerda , Remodelação Ventricular , Angiotensina II , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Imagem Cinética por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Fatores de Tempo
9.
Am J Cardiol ; 131: 49-53, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32718551

RESUMO

We aimed to assess the risk factors for left ventricle (LV) enlargement in children with idiopathic frequent ventricular premature complexes (VPC) and discuss the clinical features and treatment strategies. Children diagnosed with idiopathic frequent VPC at Xinhua Hospital affiliated to the Shanghai Jiao Tong University during 2013 to 2019 were retrospectively evaluated. Gender, age, body mass index, weight, number and sources of frequent VPC, and changes in the LV structure were analyzed and compared. A total of 29 patient showed changes in LV enlargement at diagnosis [age 7.3 ± 4.0 years, 8 (24.1%) had symptoms such as syncope, palpitations, fatigue, and dizziness], whereas 220 showed a normal LV structure [age 7.2 ± 4.5 years, 77 (32.3%) with symptoms]. Patients with LV enlargement showed a higher percentage of VPC on Holter recordings (30.2 ± 10.7 versus 9.4 ± 6.9, p < 0.05), higher prevalence of ventricular tachycardia [22 (75.9%) vs 36 (16.4%), p < 0.0001], higher number of couplets [26 (96.7%) vs 132 (60.0%), p = 0.002], higher number of trigeminy [27 (97.8%) vs 133 (83.2%), p < 0.001], higher QRS wave width [80.0 ± 5.9 vs 77.8 ± 6.8, p = 0.021], and higher incidence of right bundle branch block [11 (37.9%) vs 2 (0.9%), p < 0.001]. Multivariate analysis suggested that right bundle branch block (Odds Ratio = 143.9 p <0.001) and VPC burden (>20%) (Odds Ratio = 132.6, p <0.001) were the risk factors for LV enlargement in children with idiopathic frequent VPC. In conclusion, frequent VPC can induce prominent enlargement or LV dysfunction in children. LV enlargement are reversible after catheter ablation or medication.


Assuntos
Hipertrofia Ventricular Esquerda/etiologia , Complexos Ventriculares Prematuros/complicações , Adolescente , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco
10.
Circ Heart Fail ; 13(6): e006685, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32498621

RESUMO

BACKGROUND: Heart failure is a prominent complication of type 2 diabetes mellitus (T2D). The goal of this study was to provide longitudinal data on cardiac structure and function (and cross-sectional comparison to normal-weight and obese controls without T2D) in individuals followed from adolescence with youth-onset T2D. METHODS: In the TODAY study (Treatment Options for Type 2 Diabetes Mellitus in Adolescents and Youth), echocardiograms were performed at study years 4 to 5 and 9 to 10. Echocardiograms were also obtained at years 8 to 9 in a control population of age, race/ethnicity, and sex-matched normal-weight and obese individuals without diabetes mellitus. Study outcomes were measures of left ventricular structure and function. The cohort included 411 participants with T2D, 194 obese controls, and 51 normal-weight controls. RESULTS: At follow-up, mean participant age was 23 years, 65% women, 20% non-Hispanic white, 35% non-Hispanic black, and 39% Hispanic. Ejection fraction was <52% in 11.7% of male participants with T2D. Diastolic function declined during follow-up in participants with T2D (mitral valve lateral E/Em increased 0.72±0.12 in women and 0.50±0.17 in men; P<0.01) and was significantly higher than obese controls (women, 6.65±1.89 versus 5.66±1.37; men, 6.15±1.90 versus 5.26±1.31; P<0.0001). Predictors of adverse changes included hypertension, obesity, female sex, Hispanic and non-Hispanic black ethnicity, worse glycemic control, and elevated heart rate. Cardiac structural abnormalities, left ventricular hypertrophy, or concentric geometry, were highest in those with T2D (15.8% versus 5.7% obese versus 0% normal weight). CONCLUSIONS: Adverse changes in cardiac structure and function changed significantly from adolescence to early adulthood in participants with youth-onset T2D. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00081328.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/etiologia , Hipertrofia Ventricular Esquerda/etiologia , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Remodelação Ventricular , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/fisiopatologia , Progressão da Doença , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
12.
J Cardiovasc Magn Reson ; 22(1): 25, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32321533

RESUMO

BACKGROUND: Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. METHODS: This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). RESULTS: CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: - 24.2 ± 2.7% in cirrhosis vs - 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from - 24.9 ± 2.4% to - 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). CONCLUSIONS: Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Ecocardiografia Doppler , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Cirrose Hepática/cirurgia , Transplante de Fígado , Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico por imagem , Listas de Espera , Idoso , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular
13.
Circ Cardiovasc Imaging ; 13(3): e010171, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32114828

RESUMO

Background Cardiovascular magnetic resonance can demonstrate myocardial processes in Fabry disease (FD), such as low native T1 (sphingolipid storage) and late gadolinium enhancement (LGE, scar). Recently, high T2 (edema) has been observed in the basal inferolateral wall along with troponin elevation. We hypothesized that edema and myocyte injury would be chronically associated and have electrical, mechanical, and disease associations in FD. Methods A prospective international multicenter study was conducted on 186 consecutive FD patients (45.2±1.1 years, 58% females). Additionally, 28 patients with hypertrophic cardiomyopathy, 30 with chronic myocardial infarction and 59 healthy volunteers were included. All study participants underwent comprehensive cardiovascular magnetic resonance with T1 and T2 mapping, cines, and LGE imaging. Results LGE in the basal inferolateral wall in FD had T2 elevation (FD 58.2±5.0 ms versus hypertrophic cardiomyopathy 55.6±4.3 ms, chronic myocardial infarction 53.7±3.4 ms and healthy volunteers 48.9±2.5 ms, P<0.001), but when LGE was present there was also global T2 elevation (53.1±2.9 versus 50.6±2.2 ms, P<0.001). Thirty-eight percent of FD patients had high troponin. The strongest predictor of increased troponin was high basal inferolateral wall T2 (odds ratio, 18.2 [95% CI, 3.7-90.9], P<0.0001). Both T2 and troponin elevations were chronic over 1 year. High basal inferolateral wall T2 was associated with baseline global longitudinal strain impairment (P=0.005) and electrocardiographic abnormalities (long PR, complete bundle branch block, left ventricular hypertrophy voltage criteria, long QTc, and T-wave inversion, all P<0.05) and predicted clinical worsening after 1 year (Fabry stabilization index >20%, P=0.034). Conclusions LGE in Fabry has chronic local T2 elevation that is strongly associated with chronic troponin elevation. In addition, there is slight global T2 elevation. Both are associated with ECG and mechanical changes and clinical worsening over 1 year.


Assuntos
Doença de Fabry/diagnóstico , Hipertrofia Ventricular Esquerda/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Função Ventricular Esquerda/fisiologia , Adulto , Edema/diagnóstico , Edema/etiologia , Doença de Fabry/complicações , Doença de Fabry/fisiopatologia , Feminino , Seguimentos , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Remodelação Ventricular
14.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R894-R900, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209023

RESUMO

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats (n = 7) and mice (n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats (n = 12) and mice (n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats (n = 6) than in mice (n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC (n = 4), but they were preserved in rats (n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.


Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Pressão Ventricular , Remodelação Ventricular , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Capilares/metabolismo , Capilares/fisiopatologia , Circulação Coronária , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Antígeno Ki-67/metabolismo , Ligadura , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Miócitos Cardíacos/metabolismo , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Especificidade da Espécie , Fatores de Tempo , Troponina I/metabolismo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo
15.
Int Heart J ; 61(2): 373-379, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32173694

RESUMO

We aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), brain natriuretic peptide (BNP), and left ventricular hypertrophy (LVH) in hypertension. METHODS: This study included 386 patients with hypertension. Mann-Whitney U test and multivariate binary logistic regression analysis were used to investigate the relationship between NLR, CRP, BNP, and LVH in patients with hypertension, as well as compare the levels of NLR, CRP, and BNP in the four configurations. Receiver operator characteristic (ROC) curve was used to compare the diagnostic efficacy of NLR, CRP, and BNP on LVH. RESULTS: The NLR and CRP and BNP levels of the LVH group were significantly higher than those of the non-LVH group. In the multivariate logistic regression analysis, NLR as well as age, BMI, and SBP were associated with LVH. In addition, in patients with eccentric and concentric hypertrophy, the NLR and CRP and BNP levels were higher than those of the normal left ventricular geometry and concentric remodeling groups. The cutoff values of NLR, CRP, and BNP obtained by ROC curve were 2.185, 2.205, and 283.45, respectively, for the prediction of LVH. CONCLUSIONS: NLR is independently associated with LVH in patients with hypertension, and this is consistent with the diagnostic efficacy of CRP and BNP, which may be a simple and convenient indicator for judging LVH.


Assuntos
Hipertensão/complicações , Hipertrofia Ventricular Esquerda/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue
16.
Rev. clín. esp. (Ed. impr.) ; 220(2): 100-108, mar. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186419

RESUMO

Objetivo: La hipertrofia ventricular izquierda es el marcador de daño de órgano diana más frecuente en la hipertensión arterial. Habitualmente se realiza un ECG para su identificación. El objetivo de este trabajo es analizar la utilidad pronóstica de otras alteraciones electrocardiográficas en pacientes hipertensos, más allá de la hipertrofia ventricular. Materiales y métodos: Se incluyeron 1.003 pacientes hipertensos mayores de65años. Se recogieron factores de riesgo, historia cardiovascular previa y tratamiento médico. Se analizaron diferentes alteraciones electrocardiográficas, incluyendo índice de Sokolow-Lyon, índice de Cornell, presencia de sobrecarga ventricular y bloqueos de rama, entre otros. Se llevó a cabo un seguimiento de 2años con recogida de eventos cardiovasculares mayores (mortalidad, infarto de miocardio, accidentes cerebrovascular o ingreso por insuficiencia cardiaca). Resultados: La edad media de la población era de 72,9+/-5,8años, con un 47,5% de varones. Durante el seguimiento el 13,9% sufrieron un evento cardiovascular mayor. Estos pacientes eran de mayor edad, más fumadores y practicaban menos ejercicio físico, sin presentar diferencias en el tratamiento antihipertensivo empleado ni en el control tensional. El patrón de sobrecarga ventricular (HR: 1,93; IC95%: 1,160-3,196; p=0,011) y el bloqueo completo de rama izquierda (HR: 2,27; IC95%: 1,040-4,956; p=0,040) se comportaron como factores electrocardiográficos predictores independientes de eventos cardiovasculares mayores, no así la hipertrofia ventricular izquierda por Sokolow y/o Cornell. Conclusiones: En pacientes hipertensos, la existencia en el ECG basal de un bloqueo completo de rama izquierda o un patrón de sobrecarga ventricular identifica a una población de mayor riesgo cardiovascular


Objective: Left ventricular hypertrophy is the most common marker of target organ damage in arterial hypertension. Electrocardiograms are typically performed to identify left ventricular hypertrophy. The aim of this study was to analyse the prognostic utility of other electrocardiographic abnormalities in patients with arterial hypertension, beyond ventricular hypertrophy. Materials and methods: The study included 1003 patients older than 65years with arterial hypertension. We recorded risk factors, previous cardiovascular history and medical treatment and analysed various electrocardiographic abnormalities including the Sokolow-Lyon index, the Cornell index, ventricular overload and branch blocks. The study conducted a 2-year follow-up, recording the major cardiovascular events (mortality, myocardial infarction, stroke and hospitalisation for heart failure). Results: The study population's mean age was 72.9+/-5.8years, 47.5% of whom were men. During the follow-up, 13.9% of the patients experienced a major cardiovascular event. These patients were older, more often smokers and engaged in less physical exercise, without presenting differences in the antihypertensive therapy or blood pressure control. The ventricular overload pattern (HR: 1.93; 95%CI: 1.160-3.196; P=.011) and the complete left bundle branch block (HR: 2.27; 95%CI: 1.040-4.956; P=.040) behaved as independent electrocardiographic predictors of major cardiovascular events; however, left ventricular hypertrophy using the Sokolow and/or Cornell index did not behave as such. Conclusions: For patients with hypertension, the presence in the baseline electrocardiogram of complete left bundle branch block or a pattern of ventricular overload identifies a population at increased cardiovascular risk


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Hipertensão/fisiopatologia , Eletrocardiografia/estatística & dados numéricos , Doenças Cardiovasculares/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Seguimentos , Comportamento Sedentário , Tabagismo/epidemiologia , Fatores Etários , Bloqueio de Ramo/epidemiologia
18.
Nutrients ; 12(2)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033349

RESUMO

Obese subjects showed different cardiovascular risk depending by different insulin sensitivity status. We investigated the difference in left ventricular mass and geometry between metabolically healthy (MHO) and unhealthy (MUHO) obese subjects. From a cohort of 876 obese subjects (48.3 ± 14.1 years) without cardio-metabolic disease and stratified according to increasing values of Matsuda index after 75 g oral glucose tolerance test, we defined MHO (n = 292) those in the upper tertile and MUHO (n = 292) those in the lower tertile. All participants underwent echocardiographic measurements. Left ventricular mass was calculated by Devereux equation and normalized by height2,7 and left ventricular hypertrophy (LVH) was defined by values >44 g/m2.7 for females and >48 g/m2.7 for males. Left ventricular geometric pattern was defined as concentric or eccentric if relative wall thickness was higher or lower than 0.42, respectively. MHO developed more commonly a concentric remodeling (19.9 vs. 9.9%; p = 0.001) and had a reduced risk for LVH (OR 0.46; p < 0.0001) than MUHO, in which the eccentric type was more prevalent (40.4 vs. 5.1%; p < 0.0001). We demonstrated that obese subjects-matched for age, gender and BMI-have different left ventricular mass and geometry due to different insulin sensitivity status, suggesting that diverse metabolic phenotypes lead to alternative myocardial adaptation.


Assuntos
Intolerância à Glucose/fisiopatologia , Hipertrofia Ventricular Esquerda/epidemiologia , Resistência à Insulina/fisiologia , Obesidade Metabolicamente Benigna/fisiopatologia , Obesidade/fisiopatologia , Adulto , Glicemia/metabolismo , Ecocardiografia , Feminino , Intolerância à Glucose/complicações , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade Metabolicamente Benigna/complicações , Obesidade Metabolicamente Benigna/diagnóstico por imagem , Fenótipo , Prevalência , Fatores de Risco
19.
PLoS One ; 15(1): e0228449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32005035

RESUMO

OBJECTIVE: The main objective of this study was to evidence the potential impact of the intensity, duration and recurrence of depression on the development of arterial stiffness (AS) leading to left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) in patients with new onset depression (NOD) and recurrent depression (RD) in comparison to 33 control subjects without depression. Another aim was to identify potential predictive factors regarding the occurrence of diastolic dysfunction (DD). METHODS: Our study group included 58 patients diagnosed with NOD and 128 diagnosed with RD, without any previously diagnosed significant heart diseases. The intensity of depression was evaluated by means of the Montgomery-Asberg Depression Rating Scale (MADRS). Assessment of pulse wave velocity (PWV), left ventricular mass index (LVMI) and echocardiographic parameters characterizing DD were performed for each patient. RESULTS: The cardiology evaluations suggested an increased prevalence of AS in all patients, of significantly higher rate than in controls (p<0.001), which was statistically correlated with the severity and duration of depression. Another significant finding was an increased prevalence of DD (29.31% and 63.28%, respectively; p<0.001) correlated with the MADRS score, total duration and number of recurrences/relapses. The multivariate logistic regression analysis identified PWV, the intensity and duration of depression as significant predictive factors for the occurrence of DD. CONCLUSIONS: In our study, diastolic dysfunction was a common finding among patients with RD, but it was also noted, to a lesser extent, in those suffering with NOD. DD was associated with altered AS, and strongly correlated with the intensity and the duration of depressive symptoms. The two latter factors, together with an increased PWV, were strong predictors for the occurrence of DD.


Assuntos
Depressão/complicações , Hipertrofia Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Adulto , Estudos de Casos e Controles , Depressão/fisiopatologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Recidiva , Rigidez Vascular , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
20.
BMC Cardiovasc Disord ; 20(1): 51, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013884

RESUMO

BACKGROUND: Aortic valve regurgitation (AR) results in left ventricle (LV) volume overload (VO) leading to its dilation and hypertrophy (H). We study a rat model of severe AR induced by puncturing one or two leaflets using a catheter. Most of our studies were conducted in male animals. Recently, we started investigating if sex dimorphism existed in the AR rat model. We observed that AR females developed as much LVH as males but morphological remodeling differences were present. A head-to-head comparison of LV morphological and functional changes had never been performed in AR males (M) and females (F) using the latest modalities in cardiac imaging by echocardiography. METHODS: We performed a longitudinal study to evaluate the development of LV hypertrophy caused by chronic AR in male and female rats over 6 months. Sham-operated (sham) animals were used as controls. RESULTS: LV diastolic volumes (EDV) increased more over 6 months in sham males than in females (38% vs. 23% for EDV, both p < 0.01). AR resulted in significant LV dilation for both sexes (54% vs. 51% increase in EDV) vs. baseline values. Since normal cardiac growth was less in females, dilation from AR was relatively more important for them (88% (M) vs. 157% (F) increase in EDV over sham). AR caused LV wall thickening in both males and females. It happened sooner for AR females and was more important than in males (25% (M) vs. 56% (F) increase in septum thickness at 2 months and 10% (M) vs. 30% (F) at 6 months). We then evaluated if AR was associated with changes in LV strain using speckle-tracking 2D echocardiography. Global longitudinal strain remained similar between AR and sham animals. Circumferential strain was negatively modulated by AR but only in females and early after VO induction (13% (M) vs. 26% (F)). CONCLUSION: AR resulted in more LV dilation and quicker wall thickening in female AR rats compared to males. Global circumferential strain was negatively modulated in AR females but not in males. AR also seemed to lead to a more spherical LV shape in females whereas; it kept mostly an ellipsoid shape in males. This can influence validity of mass estimation of the dilated LV in females by echocardiography.


Assuntos
Insuficiência da Valva Aórtica/complicações , Hipertrofia Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Modelos Animais de Doenças , Feminino , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Ratos Wistar , Índice de Gravidade de Doença , Caracteres Sexuais , Fatores Sexuais , Fatores de Tempo
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