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

Abstract

Early detection of doxorubicin (DXR)-induced cardiomyopathy (DXR-ICM) is crucial to improve cancer patient outcomes and survival. In recent years, the intraventricular pressure gradient (IVPG) has been a breakthrough as a sensitive index to assess cardiac function. This study aimed to evaluate the usefulness of IVPG for the early detection of chemotherapy-related cardiac dysfunction. For this purpose, six dogs underwent conventional, speckle tracking, and color M-mode echocardiography concomitantly with pressure-and-volume analysis by conductance catheter. The cardiac function measurements were assessed before DXR administration (baseline, Pre), at the end of treatment protocol (Post), and at 1.5 years follow-up (Post2). The result showed a significant reduction in the left ventricular end-systolic pressure-volume (Emax: 4.4 ± 0.7, 6.1 ± 1.6 vs. 8.4 ± 0.8 mmHg/mL), total-IVPG (0.59 ± 0.12, 0.62 ± 0.15 vs. 0.86 ± 0.12 mmHg), and mid-IVPG (0.28 ± 0.12, 0.31 ± 0.11 vs. 0.48 ± 0.08 mmHg), respectively in Post2 and Post compared with the baseline (p < 0.05). Mid-to-apical IVPG was also reduced in Post2 compared with the baseline (0.29 ± 0.13 vs. 0.51 ± 0.11). Meanwhile, the fraction shortening, ejection fraction, and longitudinal strain revealed no change between groups. Total and mid-IVPG were significantly correlated with Emax (R = 0.49; p < 0.05, both) but only mid-IVPG was a predictor for Emax (R2 = 0.238, p = 0.040). In conclusion, this study revealed that impairment of contractility was the initial changes observed with DXR-ICM in dogs and only IVPG could noninvasively detect subclinical alterations in cardiac function. Color M-mode echocardiography-derived IVPG could be a potential marker for the early detection of doxorubicin cardiomyopathy.

Evaluation of Changes in the Cardiac Function before and after Transcatheter Edge-to-Edge Mitral Valve Repair in Healthy Dogs: Conventional and Novel Echocardiography

“…Recent echocardiographic approaches such as two-dimensional speckle tracking echocardiography (2D-STE) and intraventricular pressure gradients (IVPG) calculated from color M-mode echocardiography create a breakthrough in cardiology research for the early diagnosis of cardiac dysfunctions, as compared with other traditional methods [ 16 , 17 , 18 ]. In the present report, the echocardiographic changes were evaluated using conventional echocardiography, 2D-STE and CMME, before and weekly after the implantation of the TEER in two clinically normal dogs.…”

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

“…This requires the incorporation of novel diagnostic tools used for diastolic function evaluation. Recently, CMME-derived IVPD and IVPG showed breakthroughs in the diagnosis of diastolic dysfunction and are suggested to be included in the conventional echocardiography protocol [9]. In the present study, we studied the response of IVPD and IVPG indices to pharmacologically induced alteration in the loading conditions in rats.…”

“…A previous study showed that LV length was positively correlated with IVPD but not associated with IVPG [11]. IVPD was also reported to be sensitive to heart length within a single species [8,9]. As indicated by these reports, it is reasonable to use IVPG in experimental systems to exclude the effect of LV length, especially when the LV length changes due to medication.…”

“…IVPD obtained by CMME is considered a sensitive indicator of diastolic function [6] and has the advantage of repeatability, unlike invasive catheterization. Similarly, the IVPG exerts the same properties as IVPD without being affected by the LV length [8][9][10][11]. Generally, the length of the LV, from the mitral valve to the apex, is divided into basal, mid, and apical parts, and each part has its corresponding IVPD and IVPG indices and a defined role in the diagnosis of cardiac dysfunction.…”

“…Recently, many trials have been undertaken to incorporate these novel indices into cardiology research, particularly in diastology. 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].…”