Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), a left ventricular ejection fraction (LVEF) less than 35% has been identified as a significant risk factor for increased mortality. As a result, all studies assessing the indications and outcomes of implantable cardioverter-defibrillators and cardiac resynchronization therapy in HFrEF used this cut-off, measured by 2-dimensional echocardiography (2DE). However, many patients with HFrEF and a LVEF >35% by 2DE, who do not qualify for device therapy, still experience significant mortality. Purpose To investigate whether, in patients hospitalized with both ischemic and non-ischemic HFrEF, the LVEF measured by 3-dimensional echocardiography (3DE) could identify better patients at high risk of death, thereby indicating the need for device therapy. Methods 322 consecutive patients (60±11 years, 72% men), hospitalized for HFrEF or HFmrEF, were assessed using both 2DE and 3DE, including full-volume acquisitions of the LV. From 2D datasets, LV end-systolic (LVESV) and LV end-diastolic (LVEDV) volumes, and LVEF were estimated. From the 3D volumes, the same parameters were measured. Patients were discharged on optimal HF treatment, according to current ESC guidelines, and were followed for 24±8 months after the initial event. The primary outcome was cardiovascular death (CD). Results At admission, 43% patients were in NYHA class II, 25% in NYHA class III, and 33% in NYHA class IV. There was a similar burden of ischemic and non-ischemic etiology (52% vs 48%). Mean 2D LVEF was 31±11%, while mean 3D LVEF was 30±10% (p=NS). There were 62 CD (19%) during follow-up. Binary logistic regression for the 2D and 3DE parameters showed that only 3D LVEF was a significant predictor of death (β=-0.04, OR 0.96, 95%CI 0.93-0.98, p=0.003). By 2DE, 206 patients (64%) had LVEF <35%, of whom 47 patients died (23%) and 159 patients survived (77%), whereas by 3DE, 215 patients (67%) had LVEF <35%, of whom 60 patients died (28%) and 155 patients survived (72%). Consequently, 2D LVEF <35% identified 47 out of 62 deaths (76%), whereas 3D LVEF <35% identified 60 out of 62 deaths (97%). By ROC Analysis, 3DE was superior to 2DE for prediction of survival: AUC 0.62, p=0.03 for 3D LVEF vs. AUC 0.56, p=0.09 for 2D LVEF. Kaplan-Meier analysis (Figure) showed that 2D LVEF <35% discriminated between survivors and non-survivors with a Chi-square of 6.8, p=0.01, whereas 3D LVEF <35% discriminated between survivors and non-survivors with a Chi-square of 30.3, p<0.001. Conclusion 3DE assessment of LVEF and its cut-off of 35% enhances the identification of patients with HFrEF at high risk of death. This suggests that 3DE should be utilized for risk stratification in HFrEF, potentially leading to more accurate indications for device therapy. Survival according to 2D vs 3D LVEF
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