Noninvasive assessment of early cardiotoxicity of doxorubicin is still a problem of clinical concern. We studied whether echocardiography during afterload stress induced by angiotensin II (1,000-3,000 ng/min) allows earlier detection of left ventricular impairment than echo at rest. We compared 30 normals (N) to 30 patients with carcinoma, who had received doxorubicin at a cumulative dose of at least 360 mg/sqm. At rest echocardiograms of patients were either normal (P1; n = 24) or abnormal (P2; n = 6; fractional shortening less than 28%, distance of mitral E-point to septum greater than 7 mm). Best parameter for separation of P1 vs N was the slope K of the regression line of the relation between endsystolic diameter and systolic blood pressure (cuff-method). 38% of P1 and 100% of P2 had K-values below the range of N (less than 4.7 mm Hg/mm). Four of five patients with reduced ejection fraction assessed by scintigraphy (less than 55%) after continued therapy with doxorubicin have had, in previous echocardiographic studies, normal resting parameters but abnormal K-values. We conclude that afterload-stress increases the sensitivity of echocardiography in detecting cardiotoxicity due to doxorubicin.

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