Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background and Aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with sacubitril/valsartan (s/v) or enalapril (ena) might prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF Simpson’s Method). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (−19.8±2.8 vs −19.3±4.1%, p = 0.403 for s/v, −20.3±2.8 vs −20.0±3.6%, p = 0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (−20.9±2.1% vs −18.5±2.2, p = 0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p = 0.826 for s/v, 58.8±5.4 vs 60.7±7.1%, p = 0.419, for ena), while a borderline deterioration was noticed after treatment with placebo for six months (60.6±5.4 vs 57.7±6.7%, p = 0,045). We did not notice any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril. On the other hand, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p = 0.030) and GWW was diminished (111.5±75.7 vs 86.4±43.1 mmHg%, p = 0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p = 0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p = 0.045), GWE was diminished (95.9±2.1 vs 94.1±3.9 %, p = 0.039) and GCW did not change. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.