Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab

Background- Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Methods and Results- Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro-B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%-43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%-14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. Conclusions- In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.     

Osteoprotegerin concentrations and prognosis in acute ischaemic stroke

Abstract. Jensen JK, Ueland T, Atar D, Gullestad L, Mickley H, Aukrust P, Januzzi JL (Odense University Hospital, Denmark; Rikshospitalet, Oslo, Norway; Massachusetts General Hospital, USA). Osteoprotegerin concentrations and prognosis in acute ischaemic stroke. J Intern Med 2010; 267 : 410–417. Aim. Concentrations of osteoprotegerin (OPG) have been associated with the presence of vascular and cardiovascular diseases, but the knowledge of this marker in the setting of ischaemic stroke is limited. Methods and results. In 244 patients with acute ischaemic stroke (age: 69 ± 13 years), samples of OPG were obtained serially from presentation to day 5. Patients with overt ischaemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all‐cause mortality as the sole end‐point. Multivariable predictors of OPG values at presentation included haemoglobin (T = ?2.82; P = 0.005), creatinine (T = 4.56; P < 0.001), age (T = 9.66; P < 0.001), active smoking (T = 2.25; P = 0.025) and pulse rate (T = 3.23; P = 0.001). At follow‐up 72 patients (29%) had died. Patients with OPG ≤2945 pg mL^?1 at baseline had a significantly improved survival rate on univariate analysis (P < 0.0001); other time‐points did not add further prognostic information. In multivariate analysis, after adjustment for age, stroke severity, C‐reactive protein levels, troponin T levels, heart and renal failure concentrations of OPG independently predicted long‐term mortality after stroke (adjusted hazard ratio, 2.3; 95% CI: 1.1 to 4.9; P = 0.024). Conclusion. Osteoprotegerin concentrations measured at admission of acute ischaemic stroke are associated with long‐term mortality.     

Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy

BackgroundAmino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for the diagnosis and exclusion of congestive heart failure (HF). Little is known about the effect of race on NT-proBNP concentrations. Also, NT-proBNP levels may be higher in apparently well women, but the effect of gender on NT-proBNP concentrations in dyspneic patients is not known.Methods and ResultsNT-proBNP (Elecsys proBNP, Roche, Indianapolis, IN) was measured in 599 dyspneic patients in a prospective study. Of these, 44 were African American; 295 were female. NT-proBNP levels were examined according to race and gender in patients with and without acute HF using analysis of covariance. Receiver operating characteristic (ROC) curves assessed NT-proBNP by race and gender. Cutpoints for diagnosis (450, 900, and 1800 pg/mL for ages <50, 50 to 75, and >75 years) and exclusion (300 pg/mL) were examined in African-American and female subjects. There was no difference in the rates of acute HF between African-American and non–African-American (30% versus 35%, P = .44) or male and female (35% versus 35%, P = .86) subjects. In subjects with HF, there was no difference in median NT-proBNP concentrations between African American and non–African American (6196 versus 3597 pg/mL, P = .37). In subjects without HF, unadjusted NT-proBNP levels were lower in African-American subjects than in non–African-American subjects (68 versus 148 pg/mL, P < .03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = .53) or without HF (116 pg/mL versus 150 pg/mL, P = .62). Among African Americans, NT-proBNP had an area under the ROC for acute HF of 0.96 (P < .0001), and at optimal cutpoints, had a sensitivity of 100% and a specificity of 90%. Among females, NT-proBNP had an area under the ROC for acute HF of 0.95 (P < .0001), and had a sensitivity of 89% and a specificity of 88%; 300 pg/mL had negative predictive value of 100% in African Americans and females.ConclusionNT-proBNP is useful for the diagnosis and exclusion of acute HF in dyspneic subjects, irrespective of race or gender.     

Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography

Although epidemiologic data link biomarkers of cardiovascular risk with incident and prevalent coronary artery disease, exact anatomic relationships between biomarkers and coronary atherosclerosis as measured by coronary CT angiography remain unclear. Patients with acute chest pain who ultimately had no evidence of acute coronary syndrome underwent contrast-enhanced 64-slice coronary CT angiography to determine presence, extent and composition of coronary atherosclerotic plaque. We determined the differences in levels of blood biomarkers measured at the time of the CT scan between different CT-based atherosclerotic plaque groups. Among 313 patients (mean age: 51.6 ± 11 years, 62% male) high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-2 were associated with the extent of calcified plaque (P = 0.03 and P < 0.001), while hs-CRP and apolipoprotein A1 were associated with the extent of non-calcified plaque (P = 0.03 and P = 0.004; respectively). Despite a generally lower risk profile, subjects with exclusively non-calcified plaque had significantly higher levels of hs-CRP and oxidized low-density lipoprotein (P = 0.01 and P = 0.03; respectively) and lower levels of adiponectin (P = 0.03) when compared to subjects with calcified plaque (n = 130, 42%). Biomarkers reflecting inflammation, vascular remodeling, oxidation, and lipoprotein metabolism maybe associated with different patterns of coronary atherosclerosis as quantified by coronary CT angiography.