Global Longitudinal Strain Accuracy for Cardiotoxicity Prediction in a Cohort of Breast Cancer Patients During Anthracycline and/or Trastuzumab Treatment

<div><p>Abstract Background: The high cardiotoxicity morbidity and mortality rates associated with the antineoplastic therapy for breast cancer could be reduced with the early use of cardioprotective drugs. However, the low sensitivity of left ventricular ejection fraction limits its use in that preventive strategy. New parameters, such as global longitudinal strain, are being used in the early detection of contractile function changes. Objectives: To assess the incidence of cardiotoxicity in patients treated for breast cancer, the independent factors associated with that event, and the ability of strain to identify it early. Methods: Prospective observational study of consecutive outpatients diagnosed with breast cancer, with no previous antineoplastic treatment and no ventricular dysfunction, who underwent anthracycline and/or trastuzumab therapy. The patients were quarterly evaluated on a 6- to 12-month follow-up by an observer blind to therapy. Cox regression was used to evaluate the association of cardiotoxicity with clinical, therapeutic and echocardiographic variables. A ROC curve was built to identify the strain cutoff point on the third month that could predict the ejection fraction reduction on the sixth month. For all tests, the statistical significance level adopted was p ≤ 0.05. Results: Of 49 women (mean age, 49.7 ± 12.2 years), cardiotoxicity was identified in 5 (10%) on the third (n = 2) and sixth (n = 3) months of follow-up. Strain was independently associated with the event (p = 0.004; HR = 2.77; 95%CI: 1.39-5.54), with a cutoff point for absolute value of -16.6 (AUC = 0.95; 95%CI: 0.87-1.0) or a cutoff point for percentage reduction of 14% (AUC = 0.97; 95%CI: 0.9-1.0). Conclusion: The 14% reduction in strain (absolute value of -16.6) allowed the early identification of patients who could develop anthracycline and/or trastuzumab-induced cardiotoxicity.</p></div

IgE reactivity to <i>T</i>. <i>cruzi</i> antigen.

<p>IgE reactivity to <i>T</i>. <i>cruzi</i> antigen.</p

Characteristics of patients with progressive CCC.

<p>Characteristics of patients with progressive CCC.</p

IgA reactivity to <i>T</i>. <i>cruzi</i> antigen.

<p>IgA reactivity to <i>T</i>. <i>cruzi</i> antigen.</p

Chronic Chagas disease patients´ characteristics.

<p>Chronic Chagas disease patients´ characteristics.</p

Disease classification in CCC(P) patients before and after disease progression.

<p>Disease classification from entry into the study (BP) to after disease progression (AP) in CCC(P) sub-groups are represented (horizontal axis). The vertical axis represents the levels of disease severity according to LVEF values as described in Methods. Connecting lines link the patients’ disease classification BP and AP disease progression. Open squares represent CCC(P-WD/MD) patients, while filled triangles represent CCC(P-MOD/SD) patients. *Statistical difference between CCC(P-WD/MD) and CCC(MOD/SD) sub-groups BP calculated by chi-square test, <i>p</i> = 0.033). **** Statistical difference between CCC(P-WD/MD) and CCC(MOD/SD) sub-groups calculated by paired ANOVA-two way with Sidak’s multiple comparisons test, <i>p</i><0.0001. To perform this calculation the vertical axes were transformed in arbitrary units where: CCC(P-WD) = 4; CCC(P-MD) = 3; CCC(P-MOD) = 2; and CCC(P-SD) = 1.</p

Reactivity of IgG₁ for anti-<i>T</i>. <i>cruzi</i> antigen and correlation with ventricular ejection fraction in patients with Chagas disease.

<p>(A) Inverse of the anti-<i>T</i>. <i>cruzi</i> IgG₁ titers in sera of patients with chronic form of Chagas Disease in the indeterminate form of disease (IND), stable cardiomyopathy (CCC(S)), progressive cardiomyopathy (CCC(P)) before disease progression (BP) and progressive cardiomyopathy after disease progression (AP), respectively. The statistical analysis was calculated using ANOVA-one way plus Kruskal-Wallis post-test for multiple comparisons. (B) Inverse of anti-<i>T</i>. <i>cruzi</i> IgG₁ titers in sera of patients with progressive cardiac form of Chagas disease (CCC(P) group) before and after disease progression sub-grouped according to the severity of cardiac commitment. Patients with progressive cardiac disease without (circles) or mild (squares) (CCC(P-WD/MD)) and moderate (triangles) or severe (inverted triangles) (CCC(P-MOD/SD)) cardiac dysfunction before (open symbols) and after (filled symbols) disease progression were represented. The statistical analysis was calculated using ANOVA-two way of repeated measures with Sidak’s multiple comparisons test. The data of A and B were plotted as the mean ± standard deviation (SD). (C, D, and E) Correlation between anti-<i>T</i>. <i>cruzi</i> IgG₁ titers and ventricular ejection fraction (LVEF) in patients with the cardiac form of Chagas disease. (C) represents the correlation in patients with stable cardiac disease. (D) represents the correlation in patients with progressive cardiac disease before disease progression. Open circles, squares, triangles, and inverted triangles, represent CCC(P-WD), CCC(P-MD), CCC(P-MOD) and CCC(P-SD) patients, respectively. (E) represents the correlation in patients with progressive cardiac disease after disease progression. Filled circles, squares, triangles, and inverted triangles, represent CCC(P-WD), CCC(P-MD), CCC(P-MOD) and CCC(P-SD) patients, respectively. Spearman correlation was used to identify association between LVEF and anti-<i>T</i>. <i>cruzi</i> IgG₁ levels.</p

Natriuretic Peptide and Clinical Evaluation in the Diagnosis of Heart Failure Hemodynamic Profile: Comparison with Tissue Doppler Echocardiography

<div><p>Abstract Background: Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial. Objective: This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram. Methods: Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (> 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%. Results: Forty-three patients were included, with mean age of 69.9 ± 11.1years, left ventricular ejection fraction of 25 ± 8.0%, and BNP of 1057 ± 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP ≥ 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP > 400 pg/mL (AUC 0.62), and clinical score + CR + BNP > 1000 pg/mL (AUC 0.66). Conclusion: Physical examination, CR and BNP had a poor performance in predicting a LAP ≥ 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.</p></div

iNOS/NOS2 and NO status influence heart parasitism and cardiomyocyte integrity in <i>T. cruzi</i>-infected mice.

<p>The mice were infected with 100 blood trypomastigotes of the Colombian <i>T. cruzi</i> strain and analyzed at 40 dpi. The presence of iNOS/NOS2⁺ cells, parasite nests, inflammatory cells and Cx43 in the myocardium was immunohistochemically detected, NO concentration was evaluated by a Griess-based method and CK-MB activity levels in the serum was biochemically determined. (<b>A</b>) Increased NO levels in serum of <i>T. cruzi</i>-infected C57BL/6 mice in comparison with noninfected controls (NI). (<b>B</b>) Photomicrograph of iNOS/NOS2⁺ cells in the cardiac tissue of infected C57BL/6 mice and quantification of iNOS/NOS2⁺ cells in the cardiac tissue of infected C57BL/6 mice in comparison with noninfected controls. (<b>C</b>) Photomicrographs and quantification of parasite nests showing increased heart parasitism in <i>Nos2</i>^−/− compared with <i>T. cruzi</i>-infected C57BL/6 mice. (<b>D</b>) Similar number of inflammatory cells in the heart tissue of C57BL/6 and <i>Nos2</i>^−/−<i>T. cruzi</i>-infected mice. (<b>E</b>) CK-MB activity levels in the serum of noninfected and <i>T. cruzi</i>-infected mice revealing increased CK-MB activity in <i>T. cruzi</i>-infected mice when compared with noninfected controls. Decreased CK-MB activity in the serum of <i>Nos2</i>^−/− compared with C57BL/6 <i>T. cruzi</i>-infected mice. (<b>F</b>) Preserved expression of Cx43 in the heart tissue of <i>Nos2</i>^−/− compared with C57BL/6 infected mice. Analysis at 40 dpi of 3–5 noninfected and 5–8 infected mice/group. * <i>p</i><0.05 and ** <i>p</i><0.01. Bar = 100 µm (<b>C</b>). Bar = 50 µm (<b>F</b>).</p

Cardiomyocyte injury in <i>T. cruzi</i>-infected rhesus monkeys.

<p>Cardiomyocyte damage was assessed by immunohistochemical detection of Cx43 in the myocardium of the left ventricle and CK-MB activity levels in the serum of noninfected and chronically <i>T. cruzi</i>-infected rhesus monkeys. (<b>A</b>) Photomicrograph of myocardium section of the left ventricle of the noninfected monkey #94 showing normal pattern of Cx43 expression in intercalated discs. (<b>B</b>) Photomicrograph of myocardium section of the left ventricle of the <i>T. cruzi</i>-infected monkey #64 (23 ypi) showing normal aspect. (<b>C</b>) Photomicrograph of left ventricle section of the <i>T. cruzi</i>-infected monkey #99 (20 ypi) showing normal Cx43 pattern. (<b>D</b>) Photomicrograph of section of left ventricle of the <i>T. cruzi</i>-infected monkey #90 (20 ypi) revealing Cx43 loss in myocardial area lacking inflammation. (<b>E–F</b>). Photomicrographs of left ventricle section of the cardiopatic <i>T. cruzi</i>-infected monkey #95 (20 ypi) showing Cx43 loss in area with (<b>E</b>) intense diffuse inflammation and (<b>F</b>) the substitution of cardiomyocytes by mesenchymal cells. (<b>G</b>) Frequency of stained Cx43 area in heart sections of noninfected and chronically <i>T. cruzi</i>-infected monkeys (20–23 ypi). (<b>H</b>) Detection of CK-MB activity in the serum of noninfected and chronically <i>T. cruzi</i>-infected monkeys (20–23 ypi). (<b>I</b>) Correlation between the number of iNOS/NOS2⁺ cells in heart tissue and CK-MB activity levels in serum of rhesus monkeys. Bar = 100 µm.</p