Abstract
Simple SummaryCardiotoxicity is a serious side effect of doxorubicin in cancer patients due to the risk of development of heart failure. Early detection of doxorubicin-induced cardiomyopa-thy (DXR-ICM) has become a major objective to reduce heart failure in cancer patients. Echocar-diography is the gold standard method to diagnose cardiac diseases when cardiac dysfunction is prominent; however, it still cannot predict or early diagnose heart failure before functional de-cline. The intraventricular blood flow is characterized by intraventricular pressure gradients (IVPG) that created due to the suction of blood by the ventricles. Currently, advanced imaging techniques allow non-invasive assessment of IVPG from color M-mode echocardiography (CMME) after image processing for the clinical setting. Studies revealed that IVPG indices are promising for the early diagnosis of cardiac dysfunction. In this study, we aimed to investigate the usefulness of IVPG to detect cardiac function changes after DXR administration in dogs. 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.
Highlights
The extended life expectancy of cancer patients who have received treatment is clearly a positive development; the drawbacks of development of heart failure (HF)due to the cardiotoxic activity of the chemotherapy, for instance, doxorubicin (DXR)induced cardiomyopathy (DXR-ICM), has become a serious problem for patients who have survived the neoplastic disease
Special attention was paid to the cardiac function, and the dogs were free from any cardiac abnormalities upon auscultation of the heart, electrocardiography, and echocardiography
In the present work, we conducted for the first time a longterm study to monitor the cardiac function changes through the widely used conventional echocardiographic indices (EF, fractional shortening (FS), and global longitudinal strain (GLS)) concomitantly with novel and non-invasive indices (IVPG), and compare the intraventricular pressure gradient (IVPG) results with the gold standard indices obtained by invasive catheterization following the experimental administration of DXR
Summary
Due to the cardiotoxic activity of the chemotherapy, for instance, doxorubicin (DXR)induced cardiomyopathy (DXR-ICM), has become a serious problem for patients who have survived the neoplastic disease. Dogs receiving DXR at a cumulative dose rate of 144.8 mg/m2 showed clinical cardiotoxicity [2]. The mortality rate in patients with DXR-ICM is significantly higher compared to other cardiomyopathy patients. Only 40% of patients who underwent DXR therapy survived up to two years following the onset of HF [4]. Regardless of the usefulness of DXR in patients with malignant tumors associated with poor survival rates, its adverse effects limit its use as aggressive therapeutic options. The early and accurate detection and/or prediction of the onset of the expected HF become crucial for improving the clinical implication purposes of DXR in cancer patients
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