Does the short-term cardioprotection prevent diastolic dysfunction?

Cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer is diagnosed on left ventricular ejection fraction (LVEF) and global linear strain (GLS) worsening. Diastolic dysfunction (DD) onset during cancer treatment, influenced by baseline factors like obesity, hypertension, and diabetes, is linked to a 2.1% absolute reduction (AR) in LVEF.

To enhance understanding of this topic, we analyzed data from the SAFE trial at the end of the 2-year follow-up (EOF), adhering to the 2022 CTRCD and 2016 DD ESC guidelines. The CONSORT diagram and clinical data are shown in Figures 1 and 2. Notably, patients with hypercholesterolemia, diabetes, or hypertension were excluded from the study.

Patients who received short-term cardioprotective therapy (St-Cpt) were grouped. The effect size was estimated using Cohen's D.

At the EOF CTRCD was observed in 42.9% in the placebo arm(P) and in 3.1% in St-Cpt (p<.001). DD was noted in 58.7% of P(97% mild) and in 10.1% of St-Cpt(63% mild) (p<.001). Notably, 14.7% of patients without subclinical CTRCD exhibited DD(75% mild).

In P without CTRCD, the mean 3DLVEF reduction was 6.1%(AR 4.0) in no DD and 11.0%(AR 6.9) in DD+ (p<.001, D=1.9). For GLS it was 7.0%(AR-1.6) in no DD, and 11.6%(AR -2.6) in DD+ (p< .001, D=1.6). In P with CTRCD, the 3DLVEF reduction was 14.1%(AR 8.9) in no DD and 13.8%(AR 9.1) in DD+ (p ns, D=0.04). For GLS it was 18.9%(AR -4.3) for no DD and 19.0%(AR -4.3) in DD+ (p ns, D=0.02). In St-Cpt without CTRCD, the 3DLVEF reduction was 2.6%(AR 1.8) in no DD and 4.8%(AR 3.3) in DD+ (ns, D=0.65). For GLS it was 2.8%(AR -0.7) for no DD and 6.9%(AR -1.7) in DD+ (p=.036, D=0.96). In St-Cpt with CTRCD, the 3DLVEF reduction was 7.7%(AR 4.7) in no DD and 11.2%(AR 7.8) in DD+ (p ns, D=1.81). For GLS it was 18.5%(AR -4.1) in no DD and 19.5%(AR -5.1) in DD+ (p ns, D=0.22).

Discussion: In patients without CTRCD, the mean AR in 3DLVEF at DD onset was 2.9 points, while GLS worsened by 1 point. The effect size estimation indicated these small reductions in DD+ were meaningful, as Cohen's D value suggested a strong effect. In St-Cpt, the mean AR in 3DLVEF and GLS were smaller in DD+ (1.5 and 1 point, respectively), with only a mild effect on GLS.

In P and St-Cpt with CTRCD, the AR in 3DLVEF and GLS attributable to DD were found to be insignificant.

DD may occur in some patients without CTRCD, with a greater worsening of 3DLVEF and GLS. This finding is reinforced by the absence of common risk factors such as hypertension, hypercholesterolemia, and diabetes in these patients. Furthermore, the baseline values of 3DLVEF and GLS were within the normal range (3DLVEF: 65±4 vs. 64±4 and GLS: -23±2 vs. 23±2, for no DD and DD+, respectively). The anthracycline dosage, trastuzumab, and left-side radiotherapy were identical across both groups.

Additionally, St-Cpt appears to have a beneficial effect in mitigating the worsening of both 3DLVEF and GLS related to DD.Figure 1  Figure 2