Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma

Abstract

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

Keywords: Anthracycline-induced cardiotoxicity; Aorto-septal angle; Cancer therapeutics-related cardiac dysfunction; Sigmoid septum.

Figure 1.

Study flow diagram of patient enrollment. GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; ML, malignant lymphoma.

Figure 2.

Representative echocardiographic images of measurement of morphological parameters associated with the sigmoid septum. (A) The basal-mid ratio was defined as the ratio of basal to mid interventricular septal diameter. (B) The aorto-septal angle was defined as the angle between the anterior wall of the aorta and the ventricular septal surface.

Figure 3.

Kaplan-Meier curves for cancer therapeutics-related cardiac dysfunction (CTRCD). CTRCD-free survival was calculated according to cut-off values for (A) global longitudinal strain (GLS) and (B) the aorto-septal angle (ASA) determined by receiver operating characteristic curves. Event-free survival rates were significantly lower in groups with lower GLS and smaller ASA.

Figure 4.

C-statistics for developing cancer therapeutics-related cardiac dysfunction. Model 1 includes a history of ischemic heart disease and global longitudinal strain (GLS) as already known risk factors. Model 2 includes a history of ischemic heart disease, GLS, and incremental variables of the aorto-septal angle. The area under the curve (AUC) of Models 1 and 2 was 0.67 and 0.76, respectively.

Figure 5.

Graphic summary of a theory as to how anthracycline-induced cancer therapeutics-related cardiac dysfunction (CTRCD) develops. CTRCD develops according to the sum of baseline tissue damage plus chemotherapy-associated myocardial stress and damage. The presence of a sigmoid septum indicates some degree of baseline tissue damage. Due to the disadvantaged hemodynamics associated with a sigmoid septum, its presence can increase the severity of chemotherapy-associated tissue damage. BP, blood pressure; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction.