904-53 Left Ventricular Structure and Function Eleven Years After Doxorubicin Treatment for Childhood Leukemia: Is this a Restrictive Cardiomyopathic Process?

Abstract

We previously characterized the progressive abnormalities of left ventricular (LV) structure and function in 115 survivors of childhood acute lymphoblastic leukemia 6.4 years (mean) after completion of doxorubicin therapy. 65% of patients having received >228 mg/m 2 of doxorubicin had either increased afterload or decreased contractility, or both. Progressive increases in afterload due to a thin LV wall appeared related to an inability to increase LV mass in response to somatic growth. Of these 115 patients, 36 have died, relapsed, or are no longer followed at our institution. 8 patients had both early and late congestive heart failure. Findings noted in patients with late heart failure included normal LV size in the setting of a mean LV fractional shortening <10%, as well as frequent pulmonary hypertension, increased pulmonary resistance, and left atrial dilation. We wished to characterize the late outcome of doxorubicin cardiotoxicity by reviewing the long-term echocardiographic findings of this cohort. The remaining 79 of the original 115 patients have had echocardiographic follow-up 11.1 years (mean) after completing doxorubicin. Changes in LV structure and function adjusted for age or body surface area at 3 time points were compared: prior to doxorubicin (A), 6.4 years after doxorubicin (B), and 11.1 years after doxorubicin (C). LV fractional shortening fell from normal at A to significantly depressed at B, and remained stable but depressed at C. LV mass was normal for body surface area at A, below normal at B, and continued to become more abnormal at C (p = 0.001). LV wall thickness was normal for body surface area at A below normal at B, and continued to become more abnormal at C(p = 0.03). LV end-diastolic dimension was normal for body surface area at A and B, but during the subsequent 4.7 years, a significant fall in LV end-diastolic dimension for body surface area occurred (p = 0.03). LV afterload increased significantly from A to B, but remained elevated without further increase at C. LV contractility remained normal at all 3 times. In conclusion, the fall in LV dimension to subnormal levels with increasing follow-up, in spite of a reduced mass:volume ratio, is the pattern seen in restrictive cardiomyopathy with a loss of the capacity of the LV to dilate. Both the echocardiographic and clinical findings suggest that the moderate to long term course of children treated with boluses of doxorubicin may follow the clinical findings of a restrictive cardiomyopathic process with decreased LV compliance and a small thin-walled LV.