Sacubitril/valsartan improves heart failure functional class, left ventricular systolic and diastolic function and neurohumoral status in patients with anthracycline-induced cardiomyopathy

Abstract

Abstract Anthracycline-induced cardiomyopathy (AC-CMP) is more resistant or even refractory to conventional heart failure (HF) treatments and has a higher mortality rate as compared to HF associated with other diseases. Sacubitril/valsartan (S/V) significantly reduces cardiovascular mortality and hospitalization rate in HF patients with reduced left ventricular ejection fraction (HFrEF). There is lack of evidence of S/V efficacy and safety in patients with AC-CMP. We aimed to assess the efficacy and tolerability of S/V in patients with AC-CMP. Methods We enrolled 20 patients with anthracycline-induced HFrEF who met the indication criteria for S/V. Median age was 61 [51.5; 67], 100% women, 8 (40%) hypertensive, 1 (5%) diabetic. Seventeen (85%) patients had breast and 3 (15%) hematological cancers. Median time from anthracycline therapy was 3 [1; 11] years. Surgery due to cancer and radiation therapy were performed in 15 (75%) cases. All patients had been receiving ACE inhibitors or angiotensin II receptor blockers and were switched to S/V. 85% of patients were treated with beta-blockers, 60% – mineralocorticoid antagonists, 50% – loop diuretics. The exam (at admission and after 6 months) included 6-MWT, echo/speckle tracking, creatinine, potassium and NTproBNP level. Results Eleven (55%) patients achieved the target dose of S/V. The mean S/V dose was 289±149.1 mg. Symptomatic hypotension, hyperpotassemia or creatinine level elevation were the reasons for S/V dose reduction in 8, 1 and 2 patients, respectively. S/V wasn't withdrawn in any patient. No hospitalization due to HF or need for loop diuretics increase occurred during the follow-up. After 6 months 6-MWD increased from 416 [347.5; 477.5] to 465 [395; 513.5] m, p=0.0004. NYHA functional class improved in 50% of patients. We revealed LVEDVI decrease (61.7 [55.9; 71.6] to 57.1 [53.4; 60.1] ml/m2 p=0.002), LVEF and GLS increase (39 [34.7; 41] to 45 [39; 47]%, p=0.001 and 11 [8.7; 13.9] to 13.4 [11.9; 15.5]%, p=0.002, respectively), LAVI decrease (40.7 [32; 43.9] to 31.3 [28.6; 37.4] ml/m2, p=0.003), E/A and E/e ratios decrease (1.37 [0.7; 2.23] to 0.69 [0.64; 0.83], p=0.04, and 13 [11.3; 17.8] to 10.7 [6.9; 13.6], p=0.01, respectively). NTproBNP blood level declined from 1659 [1090; 2316] to 377 [206.8; 920] pg/ml, p<0.001. There was change in serum creatinine level but in normal ranges (from 70.3 [66.8; 80; 6] to 77 [68.6; 96.3] micromol/l, p=0.02). No significant changes in potassium level were observed. Conclusions In this pilot study S/V was well tolerated in patients with AC-CMP, but cardiologic assessment was needed for accurate dose adjustment. Therapy with S/V was associated with improvement in HF functional class and LV systolic and diastolic function as well as neurohumoral status in patients with AC-CMP. Funding Acknowledgement Type of funding source: None