Mecanismos de adaptação do coração em atletas de elite do sexo feminino: comparação com indivíduos sadios e tempo de treinamento / Heart adaptation mechanisms in elite female athletes: comparison with healthy individuals and time of training

Fundamento: O exercício intenso e continuado em atletas provoca fenótipos de remodelamento adaptativo, cujos parâmetros podem ser avaliados pela ecocardiografia convencional, e de deformação miocárdica. Assim, foi comparado o remodelamento miocárdico em atletas do sexo feminino (grupo atletas) com mulheres sedentárias da mesma faixa etária (grupo-controle) e entre atletas com maior e menor tempo de treinamento. Métodos: Foram selecionadas 57 futebolistas femininas (grupo atletas) e 25 mulheres sadias sedentárias (grupocontrole). As atletas foram divididas em dois grupos: grupo principal, com 32 atletas, e grupo sub-17, com 25 atletas. Foram determinadas, através de ecocardiografia, as dimensões, a função sistólica e diastólica das câmaras cardíacas e a deformação miocárdica (strain longitudinal, circunferencial, radial e mecânica rotacional), utilizando a estatística Z com significância de p < 0,05. Resultados: A idade dos grupos atletas, controle, principal e sub-17 foi de 22,1±6,3; 21,2±5,0; 26,5±5,1; e 16,5±0,6, respectivamente. O peso, o índice de massa corporal e a frequência cardíaca foram menores no grupo atletas. A espessura das paredes, o índice de massa do ventrículo esquerdo (VE), o volume do átrio esquerdo (AE), a fração de ejeção e as dimensões do ventrículo direito (VD) foram maiores no grupo atletas, mas dentro de valores normais. A deformação miocárdica mostrou diminuição do strain radial, da rotação basal, da rotação apical e do twist, sugerindo mecanismo de reserva contrátil. Esses parâmetros foram menores no grupo principal, que também apresentava maior espessura das paredes, maior volume do AE e maior tamanho do VD, sugerindo que o aumento da reserva contrátil se relaciona com maior tempo de treinamento. Conclusões: As atletas do sexo feminino com treinamento intenso de longa duração apresentam remodelamento adaptativo das câmaras cardíacas e aumento da reserva contrátil observada em repouso, com esses parâmetros mais acentuados nas atletas com maior tempo de treinamento.(AU)

Background: Intense continuous exercise provokes adaptive remodeling phenotypes in athletes, the parameters of which can be evaluated through conventional echocardiography and myocardial deformation. We compared myocardial remodeling in female athletes (athlete group) with sedentary women of the same age range (control group) and between older and younger athletes. Methods: A total of 57 female soccer players and 25 healthy sedentary women were selected. The athlete group was subdivided into a main group and those under 17 years of age (< 17 group). The dimensions and systolic and diastolic function of the cardiac chambers and myocardial deformation (longitudinal and circumferential, as well as radial strain and rotational mechanics) was determined through echocardiography, using the Z statistic with a significance level of p< 0.05. Results: The mean age of the athlete, control, main, and < 17 groups was 22.1 (SD, 6.3); 21.2 (SD, 5.0); 26.5 (SD, 5.1); 16.5 (SD, 0.6) years, respectively. Weight, body mass index and heart rate were lower in the athlete group. Wall thickness, left ventricular mass index, left atrial (LA) volume, ejection fraction, and right ventricular dimensions were higher in athlete group, but remained within normal ranges. Regarding myocardial deformation, there was decreased radial strain, basal rotation, apical rotation, and twisting in the athlete group, suggesting a contractile reserve mechanism. These parameters were lesser in the main athlete group, who also had greater wall thickness, greater volume in the left atrium (LA) and larger size in the right ventricle (RV), suggesting that increased contractile reserve is related to longer time spent in the sport. Conclusions: In female athletes who had undergone intense long-term training, we observed adaptive remodeling of the cardiac chambers and increased contractile reserve (at rest), and these changes were more pronounced in those with longer involvement in the sport.(AU)

Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels / 中国中药杂志

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Transcatheter Interatrial Shunts for the Treatment of Heart Failure with Preserved Ejection Fraction

Abstract Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome, which accounts for about 50% of patients with heart failure (HF). The morbidity and mortality associated with HFpEF is similar to HFrEF. Clinical trials to date have failed to show a benefit of medical therapy for HFpEF, which may due to lack of uniform phenotypes and heterogeneous population. In addition, medical therapy proven for HFrEF may not address the pathophysiologic basis for HFpEF. Left atrial remodeling and dysfunction is central to HFpEF and accounts for secondary pulmonary hypertension and pulmonary vascular congestion that frequently occurs with exertion. Interatrial shunts represent a novel treatment modality for HFpEF. These shunts allow for left atrial decongestion and a reduction in pulmonary venous hypertension during exercise leading to improvements in hemodynamics, functional status and quality of life. Trials to date have demonstrated safety and short-term efficacy of these devices for HFpEF. The long-term benefits are currently being evaluated in ongoing trials. If effective, the use of interatrial shunts may be a new therapeutic paradigm for the treatment of HFpEF.

Análise elétrica, estrutural e funcional do remodelamento atrial em pacientes com apneia obstrutiva do sono / Electrical, structural and functional analysis of atrial remodeling in patients with obstructive sleep apnea

INTRODUÇÃO: A apneia obstrutiva do sono (AOS) constitui importante fator de risco para fibrilação atrial. O remodelamento atrial é um pilar neste processo. O objetivo deste estudo foi avaliar o impacto da AOS em variáveis representativas do remodelamento atrial (elétrico, estrutural e funcional). Método: Trezentos e quatro pacientes consecutivos submetidos à polissonografia foram rastreados e 80 incluídos para realização de eletrocardiograma de 12 derivações e de alta resolução (ECGAR) e ecocardiograma bi e tridimensional. Foram divididos em grupos de acordo com: 1. Índice de Apneia-Hipopneia [AOS- (90%, 80-90% e 60minutos]. RESULTADOS: A idade média foi de 60,8±11,1 anos (60% do sexo feminino) e o IMC médio 31,95±6,5 kg/m². O grupo AOS+ apresentou menor fração de esvaziamento passivo do átrio esquerdo (FEPAE) comparado com AOS-. SatMin90%. T90 >60minutos à maior duração de onda P-ECGAR, P-máxima, P-média e P na derivação DII, menor intervalo Tinício-Tpico e menor FEPAE quando comparado ao grupo

Left atrial function and volume by magnetic resonance in patients with hereditary amyloidosis

ABSTRACT Background Left atrial (LA) enlargement is a reliable predictor of adverse cardiovascular events, and reduced atrial function is an independent risk factor for mortality in patients with amyloidosis. The objective of this study was to characterize the LA function in Mexican patients with a confirmed diagnosis of hereditary transthyretin amyloidosis (amyloid transthyretin [ATTR]) Methods All consecutive patients with diagnosis of hereditary ATTR who underwent a cardiac magnetic resonance study in the period from March 2016 to June 2017 were included in the study; the volumes and function of the left atrium were evaluated Results Patients were divided into two groups, one with and one without cardiac amyloidosis. Statistically significant differences were observed between both groups in terms of indexed maximal LA volume, 26 mL versus 35.9mL, p = 0.03; indexed minimal LA volume, 10.7 mL versus 13.6mL, p = 0.03; and indexed LA pre-contraction volume, 17 mL versus 22.4mL, p = 0.03. No statistically significant differences were observed between both groups when comparing neither different ejection volumes nor the different ejection fractions Conclusions Patients with hereditary ATTR with cardiac involvement have remodeling of the left atrium, with increased atrial volumes, without diminishing its function.

Left Atrial Stiffness: A Predictor of Atrial Fibrillation Recurrence after Radiofrequency Catheter Ablation - A Systematic Review and Meta-Analysis / Rigidez do Átrio Esquerdo: Preditor de Recorrência de Fibrilação Atrial após Ablação por Cateter de Radiofrequência - Revisão Sistemática e Metanálise

Abstract Background: Radiofrequency catheter ablation (RFCA) is a standard procedure for patients with atrial fibrillation (AF) not responsive to previous treatments, that has been increasingly considered as a first-line therapy. In this context, perioperative screening for risk factors has become important. A previous study showed that a high left atrial (LA) pressure is associated with AF recurrence after ablation, which may be secondary to a stiff left atrium. Objective: To investigate, through a systematic review and meta-analysis, if LA stiffness could be a predictor of AF recurrence after RFCA, and to discuss its clinical use. Methods: The meta-analysis followed the MOOSE recommendations. The search was performed in MEDLINE and Cochrane Central Register of Controlled Trials databases, until March 2018. Two authors performed screening, data extraction and quality assessment of the studies. Results: All studies were graded with good quality. A funnel plot was constructed, which did not show any publication bias. Four prospective observational studies were included in the systematic review and 3 of them in the meta-analysis. Statistical significance was defined at p value < 0.05. LA stiffness was a strong independent predictor of AF recurrence after RFCA (HR = 3.55, 95% CI 1.75-4.73, p = 0.0002). Conclusion: A non-invasive assessment of LA stiffness prior to ablation can be used as a potential screening factor to select or to closely follow patients with higher risks of AF recurrence and development of the stiff LA syndrome.

Resumo Fundamento: A ablação por cateter de radiofrequência (ACRF) é um procedimento padrão para pacientes com fibrilação atrial (FA) não responsivos a tratamentos prévios, que tem sido cada vez mais considerada como terapia de primeira linha. Nesse contexto, o screening para fatores de risco perioperatório tornou-se importante. Um estudo prévio mostrou que uma pressão do átrio esquerdo (AE) elevada está associada a recorrência de FA após a ablação, podendo ser secundária a um AE rígido. Objetivo: Investigar, por meio de revisão sistemática e metanálise, se a rigidez do AE é um preditor de recorrência de FA após ACRF, e discutir seu uso na prática clínica. Métodos: A metanálise foi realizada seguindo-se as recomendações do MOOSE. A busca foi realizada nas bases de dados MEDLINE e Cochrane Central Register of Controlled Trials, até março de 2018. Dois autores realizaram triagem, extração de dados e avaliação da qualidade dos estudos. Resultados: Todos os estudos obtiveram boa qualidade. Um gráfico de funil foi construído, não identificando viés de publicação. Quatro estudos prospectivos observacionais foram incluídos na revisão sistemática e 3 deles na metanálise. Foi adotado o nível de significância estatística de p < 0,05. Rigidez do AE foi um forte preditor independente da recorrência de FA após ACRF (HR = 3,55, IC 95% 1,75-4,73, p = 0,0002). Conclusão: A avaliação não invasiva da rigidez do AE antes da ablação pode ser utilizada como um potencial fator de rastreamento para a seleção ou acompanhamento de pacientes com maiores riscos de recorrência de FA e desenvolvimento da síndrome do AE rígido.

Intra-Atrial Dyssynchrony Using Cardiac Magnetic Resonance to Quantify Tissue Remodeling in Patients with Atrial Fibrillation / Dessincronia Intra-atrial à Ressonância Magnética Cardíaca para Quantificação da Remodelação Tecidual em Pacientes com Fibrilação Atrial

Abstract Background: Recent studies suggest that left atrial (LA) late gadolinium enhancement (LGE) can quantify the underlying tissue remodeling that harbors atrial fibrillation (AF). However, quantification of LA-LGE requires labor-intensive magnetic resonance imaging acquisition and postprocessing at experienced centers. LA intra-atrial dyssynchrony assessment is an emerging imaging technique that predicts AF recurrence after catheter ablation. We hypothesized that 1) LA intra-atrial dyssynchrony is associated with LA-LGE in patients with AF and 2) LA intra-atrial dyssynchrony is greater in patients with persistent AF than in those with paroxysmal AF. Method: We conducted a cross-sectional study comparing LA intra-atrial dyssynchrony and LA-LGE in 146 patients with a history of AF (60.0 ± 10.0 years, 30.1% nonparoxysmal AF) who underwent pre-AF ablation cardiac magnetic resonance (CMR) in sinus rhythm. Using tissue-tracking CMR, we measured the LA longitudinal strain in two- and four-chamber views. We defined intra-atrial dyssynchrony as the standard deviation (SD) of the time to peak longitudinal strain (SD-TPS, in %) and the SD of the time to the peak pre-atrial contraction strain corrected by the cycle length (SD-TPSpreA, in %). We used the image intensity ratio (IIR) to quantify LA-LGE. Results: Intra-atrial dyssynchrony analysis took 5 ± 9 minutes per case. Multivariable analysis showed that LA intra-atrial dyssynchrony was independently associated with LA-LGE. In addition, LA intra-atrial dyssynchrony was significantly greater in patients with persistent AF than those with paroxysmal AF. In contrast, there was no significant difference in LA-LGE between patients with persistent and paroxysmal AF. LA intra-atrial dyssynchrony showed excellent reproducibility and its analysis was less time-consuming (5 ± 9 minutes) than the LA-LGE (60 ± 20 minutes). Conclusion: LA Intra-atrial dyssynchrony is a quick and reproducible index that is independently associated with LA-LGE to reflect the underlying tissue remodeling.

Resumo Fundamento: Estudos recentes sugerem que o realce tardio com gadolínio (RTG) no átrio esquerdo (AE) pode quantificar a remodelação tecidual subjacente que abriga a fibrilação atrial (FA). No entanto, a quantificação do RTG-AE requer um trabalho intenso de aquisição por ressonância magnética e pós-processamento em centros experientes. A avaliação da dessincronia intra-atrial no AE é uma técnica de imagem emergente que prediz a recorrência da FA após ablação por cateter. Nós levantamos as hipóteses de que 1) a dessincronia intra-atrial está associada ao RTG-AE em pacientes com FA e 2) a dessincronia intra-atrial é maior em pacientes com FA persistente do que naqueles com FA paroxística. Método: Realizamos um estudo transversal comparando a dessincronia intra-atrial no AE e o RTG-AE em 146 pacientes com história de FA (60,0 ± 10,0 anos, 30,1% com FA não paroxística) submetidos à ressonância magnética cardíaca (RMC) durante ritmo sinusal antes da ablação da FA. Com utilização de RMC com tissue tracking, medimos o strain longitudinal do AE em cortes de duas e quatro câmaras. Definimos a dessincronia intra-atrial como o desvio padrão (DP) do tempo até o pico do strain longitudinal (DP-TPS, em %) e o DP do tempo até o pico do strain antes da contração atrial corrigido pela duração do ciclo (DP-TPSpreA, em %). Utilizamos a razão da intensidade da imagem (RIM) para quantificar o RTG-AE. Resultados: A análise da dessincronia intra-atrial levou 9 ± 5 minutos por caso. A análise multivariada mostrou que a dessincronia intra-atrial no AE esteve independentemente associada ao RTG-AE. Além disso, a dessincronia intra-atrial no AE foi significativamente maior em pacientes com FA persistente do que naqueles com FA paroxística. Por outro lado, não houve diferença significativa no RTG-AE entre pacientes com FA persistente e paroxística. A dessincronia intra-atrial no AE mostrou excelente reprodutibilidade e sua análise foi menos demorada (5 ± 9 minutos) do que o RTG-AE (60 ± 20 minutos). Conclusão: A dessincronia intra-atrial no AE é um índice rápido, reprodutível e independentemente associado ao RTG-AE para indicar remodelação tecidual subjacente. (Arq Bras Cardiol. 2019; 112(4):441-450)

Research Advances in Sympathetic Remodeling after Myocardial Infarction and Its Significance in Forensic Science / 法医学杂志

Sympathetic remodeling after myocardial infarction is presented as denervation, sympathetic nerve sprouting and sympathetic hyperinnervation, and is closely related to ventricular tachyarrhythmias and even sudden cardiac death at convalescence in patients with myocardial infarction. This article reviews the anatomic structure, morphology and functional remodeling of cardiac sympathetic nerve, as well as its role in healed myocardial infarction identification, which may provide references for forensic research.

Remodelagem cardíaca adicional induzida pelo treinamento militar intenso em atletas de nível competitivo / Additional cardiac remodeling induced by intense military in competitive athletes

Fundamento: A remodelagem cardíaca depende da intensidade, da duração e do método de treinamento. Objetivo: Avaliar se o treinamento realizado em uma tropa especial portuguesa incrementa a remodelagem cardíaca em uma amostra de jovens que previamente praticavam esporte de competição. Métodos: Estudo prospectivo que incluiu 76 militares candidatos a tropas especiais, 45 dos quais praticavam previamente exercício físico de nível competitivo (> 10 horas por semana). Destes militares atletas, apenas 17 concluíram com sucesso o curso. A avaliação foi realizada com 6 meses de intervalo e incluiu história clínica completa, exame físico, sinais vitais, dados antropométricos e avaliação ecocardiográfica. Considerou-se significância estatística quando p < 0,05, com intervalo de confiança de 95%. Resultados: No final do curso, verificaram-se diminuição da porcentagem de massa gorda (19,1 ± 3,3% vs. 13,1 ± 3,5%; p < 0,01), aumento da porcentagem de massa muscular (41,3 ± 2,1% vs. 44,4 ± 1,8%; p < 0,01), e diminuição da pressão arterial sistólica, diastólica e frequência cardíaca. Em relação à remodelagem cardíaca, verificaram-se aumento do diâmetro diastólico do ventrículo esquerdo (49,7 ± 3,2 mm vs. 52,8 ± 3,4 mm; p < 0,01), aumento tendencial do volume do átrio esquerdo (27,3 ± 4,5 mL/m2 vs. 28,2 ± 4,1 mL/m2; p = 0,07) e aumento da massa do ventrículo esquerdo (93,1 ± 7,7g/m2 vs. 100,2 ± 11,4 g/m2; p < 0,01). As variáveis funcionais também sofreram alterações, com aumento do S' (15 (13-16) cm/s vs. 17 (16-18) cm/s; p < 0,01) e diminuição da fração de ejeção do ventrículo esquerdo (60 ± 6% vs. 54 ± 6%; p < 0,01). Conclusão: O treinamento físico militar intenso provocou remodelagem cardíaca adicional em atletas de nível competitivo, tanto estrutural como funcional

Background: Cardiac remodeling depends on the intensity, duration, and training method. Objective: To evaluate if the training performed in a Portuguese military special operations troop increases cardiac remodeling in a sample of young individuals who previously practiced competitive sports. Methods: A prospective study involving 76 military candidates for military special operations, 45 of whom previously practiced at competitive level (> 10 hours per week). Of these military athletes, only 17 successfully completed the course. The evaluation was performed at 6 months intervals and included a complete clinical history, physical examination, vital signs, anthropometric data and echocardiographic evaluation. Statistical significance was considered when p < 0.05, with a 95% confidence interval. Results: At the end of the course, there was a decrease in the percentage of fat mass (19.1 ± 3.3% vs. 13.1 ± 3.5%; p < 0.01), an increase in the percentage of lean mass (41.3 ± 2.1% vs. 44.4 ± 1.8%; p < 0.01), and decreased systolic and diastolic blood pressure and heart rate. Regarding cardiac remodeling, there was an increase in left ventricular diastolic diameter (49.7 ± 3.2 mm vs. 52.8 ± 3.4 mm; p < 0.01), an increase trend in left atrial volume (27.3 ± 4.5 mL/m2 vs. 28.2 ± 4.1 mL/m2; p = 0.07) and increased left ventricular mass (93.1 ± 7.7 g/m2 vs.100.2 ± 11.4 g/m2 ; p < 0.01). Functional variables also changed, with an increase in S' (15 (13-16) cm/s vs. 17 (16-18) cm/s; p < 0,01) and a decrease in left ventricular ejection fraction (60 ± 6% vs. 54 ± 6%; p < 0.01). Conclusion: Intense military physical training resulted in additional cardiac remodeling in athletes of competitive level, both structural and functional

Establishment of cardiac remodeling model in FVB/N mice by intraperitoneal injection of isoproterenol / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the feasibility of intraperitoneal injection of isoproterenol (ISO) to induce cardiac remodeling in FVB/N mice.</p><p><b>METHODS</b>Forty-eight FVB/N mice were divided into back subcutaneous saline group (subcutaneous saline group), intraperitoneal saline group, back subcutaneous ISO group (subcutaneous ISO group), and intraperitoneal ISO group according to the route of administration of saline or ISO. ISO (30 μg/g body weight/day) was given to the subcutaneous ISO group and the intraperitoneal ISO group, twice daily with an interval of 12 hours, for 14 consecutive days. The subcutaneous saline group and the intraperitoneal saline group were injected with an equal volume of saline. The left ventricular end-diastolic posterior wall thickness was measured by echocardiography, and the ratio of heart weight to tibia length was determined. Hematoxylin-eosin staining was used to determine the myocardial fiber diameter. Picric-sirius red staining was used to determine the myocardial collagen deposition area. Quantitative real-time PCR was used to measure the mRNA expression of collagen I.</p><p><b>RESULTS</b>Compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups, the intraperitoneal ISO group had increased sizes of the cardiac cavity and the heart. Compared with the subcutaneous saline and intraperitoneal saline groups, the subcutaneous ISO group showed no significant changes in the gross morphology of the cardiac cavity and the heart. The intraperitoneal ISO group showed significant increases in the ratio of heart weight to tibia length, myocardial fiber diameter, left ventricular end-diastolic posterior wall thickness, myocardial collagen area percentage, and the mRNA expression of collagen I compared with the subcutaneous ISO, subcutaneous saline, and intraperitoneal saline groups (P<0.01). There were no significant differences in the above five indices between the subcutaneous ISO group and the subcutaneous saline and intraperitoneal saline groups (P>0.05). No significant difference in the mortality rate was found between the subcutaneous ISO and intraperitoneal ISO groups (P>0.05).</p><p><b>CONCLUSIONS</b>Intraperitoneal injection of ISO can induce cardiac hypertrophy and fibrosis in FVB/N mice.</p>

Role of ACE2-Ang (1-7)-Mas receptor axis in heart failure with preserved ejection fraction with hypertension / 中南大学学报(医学版)

To investigate changes in the angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) [Ang (1-7)] and to explore the role of ACE2-Ang (1-7)-Mas receptor axis in hypertension with heart failure with preserved ejection fraction (HFPEF).
 Methods: A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction (LVEF>50%) were recruited and patients were divided into a hypertension group (HBP) and a heart failure with preserved ejection fraction group (HFpEF) according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays (ELISA) method was used to detect concentration of Ang (1-7), ACE2, angiotensin II (Ang II), brain natriuretic peptide (BNP) in plasma. Male Sprague- Dawley (SD) rats was randomly divided into 2 groups: An HFpEF group (n=16) and a sham group (n=8). Rats (n=8) in the AAC group were given Ang (1-7) [0.5 mg/(kg.d), intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin (HE) staining. The protein expressions of angiotensin converting enzyme (ACE), ACE2, and Mas receptor were detected by Western blot.
 Results: The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group (P0.05), whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group (P0.05).
 Conclusion: ACE2 and Ang (1-7) are important predictive factors for the severity of heart failure and myocardial remodeling of HFpEF with hypertension; ACE2-Ang (1-7)-Mas receptor axis may play a protective role in preventing myocardial remodeling in HFpEF with hypertension.

Left Atrial Mechanical Function and Aortic Stiffness in Middle-aged Patients with the First Episode of Atrial Fibrillation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In the early stages of atrial remodeling, aortic stiffness might be an indication of an atrial myopathy, in particular, atrial fibrosis. This study aimed to investigate the association between left atrial (LA) mechanical function, assessed by two-dimensional speckle tracking echocardiography, and aortic stiffness in middle-aged patients with the first episode of nonvalvular atrial fibrillation (AF).</p><p><b>METHODS</b>This prospective study included 34 consecutive patients with the first episode of AF, who were admitted to Kartal Koşuyolu Research and Training Hospital between May 2013 and October 2015, and 31 age- and gender-matched healthy controls. During the 1 st month (mostly in the first 2 weeks) following their first admission, 34 patients underwent the first pulse wave measurements. Then, 21 patients were recalled for their second pulse wave measurement at 11.8 ± 6.0 months following their initial admission. Echocardiographic and pulse wave findings were compared between these 34 patients and 31 healthy controls. We also compared the pulse wave and echocardiographic findings between the first and second measurements in 21 patients.</p><p><b>RESULTS</b>Pulse wave analysis showed no significant differences between the AF patients and healthy controls with respect to PWV (10.2 ± 2.5 m/s vs. 9.7 ± 2.1 m/s; P = 0.370), augmentation pressure (9.6 ± 7.4 mmHg vs. 9.1 ± 5.7 mmHg; P = 0.740), and aortic pulse pressure (AoPP; 40.4 ± 14.0 mmHg vs. 42.1 ± 7.6 mmHg, P = 0.550). The first LA positive peak of strain was inversely related to the augmentation pressure (r = -0.30; P = 0.02) and aortic systolic pressure (r = -0.26, P = 0.04). Comparison between the two consecutive pulse wave measurements in 21 patients showed similar results, except for AoPP. In 21 patients, the AoPP at the second measurement (45.1 ± 14.1 mmHg) showed a significant increase compared with AoPP at the first measurement (39.0 ± 10.6 mmHg, P = 0.028), which was also higher than that of healthy controls (42.1 ± 7.6 mmHg, P = 0.000).</p><p><b>CONCLUSION</b>The association between aortic stiffness with reduced atrial strain and the key role of AoPP in the development of AF should be considered when treating nonvalvular AF patients with normal LA sizes.</p>

Discordant Relationships between Systemic Inflammatory Markers and Burden of Oxidative Stress in Patients with Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Oxidative stress (OS) plays an important role in the pathophysiology of atrial fibrillation (AF) by amplifying the inflammatory cascade, wherein augmented inflammation facilitates the atrial electrical remodeling process. Few studies have investigated the possible link between systemic inflammation and OS in AF. SUBJECTS AND METHODS: A total of 220 consecutive patients with AF (117 patients) or healthy controls (103 patients) were enrolled. Among the 117 AF patients, 65 paroxysmal AF (PaAF) and 52 persistent AF (PeAF) patients were included. The level of 8-iso-prostaglandin F2α (8-iso-PGF2α) was measured as a marker of OS burden. We evaluated the correlations between 3 systemic inflammatory markers, high-sensitivity C-reactive protein (hsCRP), neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW), and 8-iso-PGF2α. RESULTS: The 8-iso-PGF2α concentration in both PaAF and PeAF patients was higher than that of controls (p<0.001 and p=0.024, respectively). The NLR and RDW of PeAF patients were higher than those of both control and PaAF patients (p=0.041 and p=0.031 for NLR, p=0.057 and p=0.031 for RDW, respectively). There were no correlations between specific inflammatory markers and the 8-iso-PGF2α in AF. The 8-iso-PGF2α level decreased gradually with an increase in AF duration (p=0.008), contrary to the graded increase in hsCRP. Multiple regression analysis indicated that AF duration persisted as a significant determinant of 8-iso-PGF2α (β=−0.249, p=0.044). CONCLUSION: Systemic inflammatory marker levels were not proportional to the levels of 8-iso-PGF2α, an OS marker, in AF.

The Impact of the CHA₂DS₂-VASc Score on Recurrence of Atrial Fibrillation after a Single Catheter Ablation and Atrial Remodeling in Patients with Non-Valvular Atrial Fibrillation

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the impact of the CHA₂DS₂-VASc score on atrial fibrillation (AF) recurrence after a single catheter ablation procedure in patients with non-valvular AF. We also investigated the correlation between CHA₂DS₂-VASc score and atrial substrate. SUBJECTS AND METHODS: This study evaluated 151 patients who underwent catheter ablation of non-valvular AF. The study population was stratified into group 1 (<2, n=72) and group 2 (≥2, n=79) by CHA₂DS₂-VASc score. The CHA₂DS₂-VASc score was analyzed as a continuous and categorical value for evaluating its impact on AF recurrence after catheter ablation. The left atrial voltage data were analyzed by the categorical values of this score. RESULTS: Post-ablation recurrence (31.6% vs. 18.1%, p=0.046) was observed more frequently in group 2. The mean area of the lowvoltage zone was 75.64±24.81 cm² and 94.44±28.09 cm² in groups 1 and 2, respectively (p=0.005). The left atrial mean voltage in group 2 was 0.99±0.31 mV, significantly lower than that (1.49±0.67 mV, p=0.001) in group 1. The CHA₂DS₂-VASc score was the independent predictor with a modest predictive value for AF recurrence after catheter ablation. CONCLUSION: Our study showed that CHA₂DS₂-VASc score was associated with atrial remodeling and could be useful in stratifying post-ablation recurrence in patients with non-valvular AF.

Role of cyclic adenosine monophosphate response element binding protein in ventricular pacing induced cardiac electrical remodeling in a canine model / 中华心血管病杂志

<p><b>OBJECTIVE</b>This project is designed to explore the potential role of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in cardiac electrical remodeling induced by pacing at different ventricular positions in dogs.</p><p><b>METHODS</b>An animal model by implanting the pacemakers in beagles was established. According to the different pacing positions, the animals were divided into 4 groups:conditional control group (n=6), left ventricle pacing group (n=6), right ventricle pacing group (n=6) and bi-ventricle pacing group (n=6). Cardiac and electrical remodeling were observed by echocardiography, electrocardiogram and plasma BNP. Myocardial pathology and protein expression of extracellular regulated protein kinases1/2 (ERK1/2), P38 mitogen activated protein kinases (P38 MAPK) and CREB were examined at 4 weeks post pacing.</p><p><b>RESULTS</b>Cardiac structure and plasma BNP level were similar among 4 groups (all P>0.05). Electrocardiogram derived Tp-Te interval was significantly prolonged post pacing (92±11, 91±10, and 79±13 ms vs. 60±12 ms), and the Tp-Te interval in bi-ventricle pacing group was shorter than in left or right ventricle pacing group (P < 0.05). Western blot results showed that the expression of p-ERK1/2 in left ventricular myocardium of left ventricle pacing group, right ventricular myocardium of right ventricle pacing group and bi-ventricular myocardium of bi-ventricle pacing group was 2.7±0.4, 2.4±0.2, 1.7±0.1 and 1.9±0.2, respectively, the expression of p-P38 MAPK was 1.9±0.3, 1.7±0.2, 0.8±0.1 and 1.1±0.1, respectively, and the expression of p-CREB was 2.1±0.2, 2.0±0.2, 2.7±0.4 and 2.6±0.3, respectively. The p-ERK1/2 and p-P38 MAPK expression of bi-ventricle pacing group was lower,but the p-CREB expression was higher compared to the other pacing groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Ventricular pacing could induce electrical remodeling evidenced by prolonged Tp-Te interval and increased phosphorylation of ERK1/2 and p38 MAPK and reduced phosphorylation of CREB. Compared with single ventricle pacing, bi-ventricle pacing could attenuate electrical remodeling in this model.</p>

Relation between Left Atrial Remodeling in Young Patients with Cryptogenic Stroke and Normal Inter-atrial Anatomy / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: To investigate an association between left atrial (LA) structural and P wave dispersion (PWD) during sinus rhythm, and electrical remodeling in cryptogenic stroke (CS) patients. METHODS: Forty CS patients and 40 age- and sex-matched healthy controls were enrolled. P wave calculations were based on 12-lead electrocardiography (ECG) at a 50-mm/s-paper speed with an amplitude of 10 mm/mV. Difference between the maximum and minimum P wave duration was the P wave dispersion (PWD=Pmax-Pmin). LA deformation was evaluated by speckle tracking echocardiography within 3 days of the acute event. RESULTS: PWD was 30.1+/-7.0 ms and 27.4+/-3.5 ms in CS and control group (P=0.02), whereas LA maximum volume index [LAVImax] was 20.4+/-4.5 mL/m2 and 19.9+/-2.4 mL/m2 in CS and control group, respectively (P = 0.04). While global peak LA strain was [pLA-S] (LA reservoir function) 41.4 +/- 6.3% and 44.5 +/- 7.1% in CS and control group, (P = 0.04), global peak late diastolic strain rate values [pLA-SRa] (LA pump function) were 2.5 +/- 0.4% and 2.9 +/- 0.5% in CS and control group, respectively (P = 0.001). A mild and a strong negative correlation between global pLA-S and LAVImax (r=-0.49; P<0.01), and between PWD and global pLA-S (r = -0.52; P < 0.01), respectively, was observed in CS. CONCLUSIONS: Increased PWD is associated with impaired LA mechanical functions and enlargement, and involved in the pathophysiology of AF or an AF-like physiology in CS.

Interatrial septal thickness as a marker of structural and functional remodeling of the left atrium in patients with atrial fibrillation

BACKGROUND/AIMS: There have been reports that interatrial septal (IAS) thickness is increased in patients with atrial fibrillation (AF). This study was performed to investigate whether IAS thickness determined by transthoracic echocardiography (TTE) represents the amount of left atrium (LA) structural and functional remodeling. METHODS: The study population consisted of 104 consecutive patients who underwent catheter ablation (CA) for AF (paroxysmal atrial fibrillation [PAF], 82; persistent atrial fibrillation [PeAF], 22). IAS thickness and left atrium volume (LAV) using TTE, and LA voltage (LAVOL) using 3-dimensional electroanatomical mapping system were assessed during sinus rhythm. RESULTS: IAS thickness was significantly correlated with maximal LAV (LAVmax) (r = 0.288, p = 0.003), mean LAVOL (r = -0.537, p or = 2) compared to other groups according to CHA2DS2-VASc score (p = 0.019). During a follow-up of 19.6 months, 23 subjects (22.1%; PAF, 17; PeAF, 6) had recurrence of arrhythmia. Univariate analysis showed that LAVmax, minimal LAV, mean LAVOL, LVEFtotal, LVEFactive, and IAS thickness were associated with recurrence of arrhythmia. However, on multivariate analysis, only mean LAVOL and LAEFactive were independent risk factors for recurrence. CONCLUSIONS: Although IAS thickness showed significant correlations with parameters for LA structural and functional remodeling, this parameter alone could not independently predict recurrence of arrhythmia after CA for AF.

Mitochondrial DNA 4977bp Deletion Mutation in Peripheral Blood Reflects Atrial Remodeling in Patients with Non-Valvular Atrial Fibrillation

PURPOSE: Recently, mitochondrial DNA 4977bp deletion (mtDNA4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA4977-mut in peripheral blood among patients with non-valvular AF. MATERIALS AND METHODS: Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA4977-mut in peripheral blood of 212 patients (51.1+/-13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects. RESULTS: The overall frequency of peripheral blood mtDNA4977-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA4977-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA4977-mut were older (58.1+/-11.9 years old vs. 48.8+/-11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension (p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio (p<0.001), as well as lower endocardial voltage (p=0.035), and slower conduction velocity (p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA4977-mut in peripheral blood. CONCLUSION: mtDNA4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.

Impact of Atrial Fibrillation Ablation on Left Ventricular Filling Pressure and Left Atrial Remodeling / Impacto da Ablação da Fibrilação Atrial na Pressão de Enchimento Ventricular Esquerdo e Remodelamento Atrial Esquerdo

Background: Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process. Objective: To evaluate the impact of AF ablation on estimated LV filling pressure. Methods: A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation. Results: One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m2 ± 10.6 mL/m2 to 22.6 mL/m2 ± 1.1 mL/m2, p < 0.001) compared to the non-successful group (37.7 mL/m2 ± 14.3 mL/m2 to 37.5 mL/m2 ± 14.5 mL/m2, p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001). Conclusion: Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure. .

Fundamento: A disfunção diastólica do ventrículo esquerdo (VE) está associada a novos episódios de fibrilação atrial (FA), e a estimativa das pressões de enchimento do VE através da razão E/e' está relacionada a um pior prognóstico em pacientes com FA. Entretanto, não se sabe se a restauração do ritmo sinusal pode reverter este processo. Objetivo: Avaliar o impacto da ablação da FA na estimativa da pressão de enchimento do VE. Métodos: Um total de 141 pacientes foi submetido à ablação por radiofrequência (RF) para o tratamento da FA refratária a drogas. Foi realizado ecocardiograma transtorácico 30 dias antes e 12 meses após a ablação. Foram avaliados os parâmetros funcionais do VE, volume do átrio esquerdo indexado (VAEi) e Doppler transmitral pulsado e Doppler tecidual do anel mitral (e' e E/e'). Dezoito pacientes apresentavam FA paroxística, 102 persistente e 21 pacientes FA persistente de longa duração. O acompanhamento incluiu ECG e monitoramento pelo sistema Holter 24h, 3, 6 e 12 meses após a ablação. Resultados: Cento e dezessete pacientes (82,9%) não apresentaram FA durante o acompanhamento (média de 18 meses ± 5 meses). O VAEi apresentou redução significativa no grupo com sucesso (30,2 mL/m2 ± 10,6 mL/m2 para 22,6 mL/m2 ± 1,1 mL/m2, p < 0,001) em comparação ao grupo sem sucesso (37,7 mL/m2 ± 14,3 mL/m2 para 37,5 mL/m2 ± 14,5 mL/m2, p = ns). A melhora da estimativa da pressão de enchimento do VE, avaliada através da redução na razão E/e', foi observada apenas após ablação com sucesso (11,5 ± 4,5 vs. 7,1 ± 3,7, p < 0,001), não sendo observada em pacientes com FA recorrente (12,7 ± 4,4 vs. 12 ± 3,3, p = ns). A taxa de ...