Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca2+-Handling Protein Expression That is Not Reversed by Exercise Training.

Background Patients treated for breast cancer have a high incidence of cardiovascular complications. In this study, we evaluated the impact of breast cancer on cardiac function and cardiomyocyte Ca2+-handling protein expression. We also investigated whether exercise training (ET) would prevent these potential alterations. Methods and Results Transgenic mice with spontaneous breast cancer (mouse mammary tumor virus-polyomavirus middle T antigen [MMTV-PyMT+], n=15) and littermate mice with no cancer (MMTV-PyMT-, n=14) were studied. For the ET analysis, MMTV-PyMT+ were divided into sedentary (n=10) and exercise-trained (n=12) groups. Cardiac function was evaluated by echocardiography with speckle-tracking imaging. Exercise tolerance test was conducted on a treadmill. Both studies were performed when the tumor became palpable and when it reached 1 cm3. After euthanasia, Ca2+-handling protein expression (Western blot) was evaluated. Exercise capacity was reduced in MMTV-PyMT+ compared with MMTV-PyMT- (Pinteraction=0.031). Longitudinal strain (Pgroup <0.001) and strain rate (Pgroup=0.030) were impaired. Cardiomyocyte phospholamban was increased (P=0.011), whereas phospho-phospholamban and sodium/calcium exchanger were decreased (P=0.038 and P=0.017, respectively) in MMTV-PyMT+. No significant difference in sarcoplasmic or endoplasmic reticulum calcium 2 ATPase (SERCA2a) was found. SERCA2a/phospholamban ratio was reduced (P=0.007). ET was not associated with increased exercise capacity. ET decreased left ventricular end-systolic diameter (Pgroup=0.038) and end-diastolic volume (Pgroup=0.026). Other morphological and functional cardiac parameters were not improved by ET in MMTV-PyMT+. ET did not improve cardiomyocyte Ca2+-handling protein expression. Conclusions Breast cancer is associated with decreased exercise capacity and subclinical left ventricular dysfunction in MMTV-PyMT+, which is at least partly associated with dysregulation of cardiomyocyte Ca2+ handling. ET did not prevent or reverse these changes.

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy / Função Atrial Esquerda em Pacientes com Miocardiopatia Chagásica Crônica

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

A doença de Chagas é uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a função do átrio esquerdo (AE) nessa doença.

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy.

BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e' (average) with the reservoir and pump functions (TEF and AEF), and a positive correlation of e' (average) with s' wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An impairment of LA functions in Chagas cardiomyopathy was observed.

Índices regionais de deformação (Strain/Strain Rate) em neonatos normais / Regional deformation indices (Strain/Strain Rate) in healthy neonates

Introdução: O Doppler tecidual (DT) evoluiu para a determinação da deformação miocárdica regional pela medida do strain rate (SR) e strain (ε) longitudinal (L) e radial (R) unidimensionais. Objetivos: Determinar padrões de normalidade em neonatos nas primeiras 24 horas de vida e estabelecer valores de referência. Casuística e Método: Foram selecionados 55 neonatos, com idade média de 20,14 ± 14,0 horas. Por meio dos cortes apical e paraesternal, em três ciclos cardíacos consecutivos, digitalmente obtidos com taxas de 300 ± 50 ciclos/s, foram realizadas medidas dos componentes sistólico, diastólico inicial e final das curvas de SR/ε, utilizando programa específico. Comparações múltiplas entre paredes e segmentos foram feitas. Resultados: Verificou-se diferença significativa na deformação longitudinal entre as medidas do SR/ε sistólicos do segmento basal da parede septal, em relação à apical (-1,89 ± 0,60, -25,86 ± 4,83 versus -1,66 ± 0,22, -24,23 ± 3,48), P= 0,04 e P= 0,02. A deformação longitudinal regional do VD também não foi homogênea, com diferenças significantes entre os segmentos basal e apical. Os valores absolutos de SR/ε e todos os seus componentes foram maiores na direção R, quando comparados com a L (SR sistólico 2,98 ± 0,78 s-1 versus (-)1,89 ± 0,60 s-1ε sistólico 53,8% ± 19% versus (-) 24,8% ± 3% P< 0,01). A variabilidade interobservador da medida do SR/ε foi de 0,7% e 1,2%, respectivamente. Conclusão: Os índices regionais de deformação miocárdica baseados no Doppler (SR/ε) constituem técnica clínica reproduzível em neonatos, permitindo a análise da função regional em diferentes segmentos do VE e VD. Representam parâmetros novos, não invasivos e independentes da interpretação visual, podendo ser utilizados no diagnóstico de acometimento cardíaco do neonato.

Usefulness of a new proposed tissue Doppler imaging global function index in hypertrophic cardiomyopathy.

BACKGROUND: A global function index (GFI) derived from tissue Doppler imaging (TDI) has been proposed to improve the diagnosis of hypertrophic cardiomyopathy (HCM). We aimed to evaluate the usefulness of this index in a large selected HCM population. METHODS: GFI =[E/Ea]/Sa, was calculated at mitral annulus lateral and septal borders in 164 HCM patients and in 40 healthy volunteers. Group comparisons and correlations between GFI and other variables were performed. RESULTS: Of the 164 patients, 69 (42%) had a peak gradient >30 mmHg in the left ventricle outflow tract (LVOT). GFI (lateral or septal) was not normally distributed. There were differences among controls, obstructive HCM, and nonobstructive HCM (P < 0.0001), but significant overlap of GFI values were observed between groups. GFI was correlated to septal thickness (r = 0.44; P < 0.0001), left atrial diameter (r = 0.52; P < 0.0001), and LVOT gradient (r = 0.58; P < 0.0001). CONCLUSION: In a selected HCM population, GFI was limited by its asymmetrical distribution and significant overlap of values between groups. Further studies are necessary to verify the reliability of GFI in the clinical practice and its position among other tissue Doppler indices.