New insight into the intraventricular pressure gradient as a sensitive indicator of diastolic cardiac dysfunction in patients with childhood cancer after anthracycline therapy

Abstract

Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in survivors of childhood cancer. The intraventricular pressure gradient (IVPG) of the left ventricle (LV) is the suction force of blood from the left atrium to the LV apex during early diastole and is a sensitive indicator of diastolic function. We assessed IVPG as a new indicator of the cardiac dysfunction in survivors of childhood cancer after anthracycline therapy. We performed a prospective echocardiographic study on 40 survivors of childhood cancer aged 6-26 years who received anthracycline therapy (group A) and 53 similar-age normal controls (group N).The subjects were divided into the younger groups, N1 and A1 (age <16 years); and older groups, N2 and A2 (age ≧16 years). IVPG was calculated using color M-mode Doppler imaging of the mitral inflow using Euler's equation. Total IVPG was divided into the basal and mid-to-apical IVPG to demonstrate more clearly the mechanisms of the LV diastolic suction force. The total anthracycline dose was 16.2-600.0 mg/m 2 (median 143.5 mg/m 2 ). Total IVPG significantly decreased in group A2 compared with that in group N2 (0.39 + 0.07 vs. 0.29 + 0.11 mmHg/cm; p = 0.010). The mid-to-apical IVPG significantly decreased in groups A1 and A2 compared with that in groups N1 and N2, respectively (N1 vs.

The Utility of Intraventricular Pressure Gradient for Early Detection of Chemotherapy-Induced Subclinical Cardiac Dysfunction in Dogs

“…During the early diastolic period, the LV works as an effective pump, actively drawing blood from the left atrium into the LV apex, without any elevation of left atrial pressure. This suction force created by the pressure gradient from the left atrium to the LV apex is a major determinant of adequate filling in the early diastole during normal cardiac function [16,45,46]. The IVPG has been recognized as an index of diastolic function in early diastole [14]; however, in the present study, IVPG was decreased even though the diastolic function was preserved as indicated by the non-significant change in Tau and left ventricular end-diastolic pressure.…”

“…At the same time, ATP-consuming actin-myosin decoupling, known as "active relaxation," also occurs. While basal-IVPG reflects left atrial pressure, mid-and mid to apical-IVPG are affected by both elastic recoil and active relaxation [45]. In the present study, the impairment of contractility may have been the reason for the mid-IVPG decline that may be developed due to a decrease in elastic recoil.…”

“…In other studies, which used EF and FS as predictors of deterioration in contractility, there was a possibility that the potential impairment of contractility could not be detected because of the poor sensitivity of conventional methods compared with invasive measurement, even though a decrease in contractility may have already occurred. For these reasons, undoubtedly, a more sensitive diagnostic index is urgently needed for saving non-responder patients [45]. Thus, our findings stress the importance of detecting a preceding deterioration in systolic function in DXR-ICM by measuring the IVPG.…”

Effect of Loading Changes on the Intraventricular Pressure Measured by Color M-Mode Echocardiography in Rats

“…Results revealed that Tau, the LV relaxation time constant measured by cardiac catheterization, was negatively correlated with total, basal, and mid IVPD under various loading states in dogs [8], while mid-to-apical IVPG was considered as a contractility index since it was well correlated with Emax, the contractility index, in chemotherapy-induced cardiomyopathy in dogs [9]. Total and mid-to-apical IVPG were identified as reliable predictors for children's survival after chemotherapy [13]. Besides, in rat models, IVPG was assessed during the development and after medication of LV hypertrophy and uremic cardiomyopathy [10,15].…”

“…For instance, it was reported that basal IVPD increases when congestion progresses, whereas mid IVPD decreases when diastolic dysfunction progresses [8,12]. Mid-to-apical IVPG was found to reflect the active relaxation of the LV during diastole, whereas the apical IVPG plays the main role in actively sucking the blood into the ventricle [13,14].…”