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.

Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound.

Two-dimensional (2-D) planimetry is limited by the technical demands, time, and observer variability required to locate the minimal orifice area, limiting the confident clinical reporting of mitral valve area (MVA). In 27 consecutive patients, MVA was determined independently by 2 observers using the conventional 2-D method and a new 3-D-guided method. Using a matrix-array probe, the valve was visualized in a long-axis view and a cursor steered to intersect the leaflet tips and provide a perpendicular short-axis plane viewed side-by-side. Two-dimensional and 3-D-guided methods allowed planimetry in 24 patients. Consistent with better orifice localization, 3-D guidance eliminated the overestimation of internal orifice diameters in the planimetered short-axis view relative to the limiting diameter defined by the long-axis view (for 3-D guidance, 0.73 +/- 0.20 vs 0.73 +/- 0.21 cm, p = 0.98, vs 0.90 +/- 0.27 cm in the 2-D short-axis view, p <0.01). Accordingly, mean values for the smallest orifice area by 3-D guidance were less than by 2-D imaging (1.4 +/- 0.5 vs 1.5 +/- 0.5 cm(2), p <0.01), changing the clinical severity classification in 11 of 24 patients (46%). The 2-D method also overestimated MVA relative to 3-D guidance compared with Doppler pressure halftime and (n = 6) Gorlin areas. Phantom studies verified no differences in resolution for the 2 acquisition modes. Three-dimensional guidance reduced intraobserver variability from 9.8% to 3.8% (SEE 0.14 to 0.06 cm(2), p <0.01) and interobserver variability from 10.6% to 6.1% (SEE 0.15 to 0.09 cm(2), p <0.02). In conclusion, matrix-array technology provides a feasible and highly reproducible direct 3-D-guided method for measuring the limiting mitral orifice area.

Quantitative assessment of regional myocardial function in mice by tissue Doppler imaging: comparison with hemodynamics and sonomicrometry.

BACKGROUND: Tissue Doppler imaging (TDI) is a novel echocardiographic method to quantify regional myocardial function. The objective of this study was to assess whether myocardial velocities and strain rate (SR) could be obtained by TDI in mice and whether these indices accurately quantified alterations in left ventricular (LV) systolic function. METHODS AND RESULTS: TDI was performed in 10 healthy mice to measure endocardial (v(endo)) and epicardial systolic velocities and SR. In further experiments, TDI indices were compared with dP/dt(max) and with sonomicrometer-derived regional velocities, at rest and after administration of dobutamine or esmolol. TDI indices were also studied serially in 8 mice before and 4 and 7 hours after endotoxin challenge. Myocardial velocities and SR were obtained in all mice with low measurement variability. TDI indices increased with administration of dobutamine (v(endo) from 2.2+/-0.3 to 3.8+/-0.2 cm/s [P<0.01]; SR from 12+/-2 to 20+/-2 s(-1) [P<0.05]) and decreased with administration of esmolol (v(endo) 1.4+/-0.2 cm/s [P<0.05]; SR 6+/-1 s(-1) [P<0.01]). Both indices correlated strongly with dP/dt(max) (r2=0.79 for SR and r2= 0.69 for v(endo); both P<0.0001). SR and shortening fraction were predictors of dP/dt(max) even after adjustment for the confounding effect of the other variables. V(endo) correlated closely with sonomicrometer-measured velocity (r2=0.71, P<0.0005). After endotoxin challenge, decreases in both v(endo) and SR were detected before decreases in shortening fraction became manifest. CONCLUSIONS: Myocardial velocities and SR can be measured noninvasively in mice with the use of TDI. Both indices are sensitive markers for quantifying LV global and regional function in mice.