4.2 The electrifying performance of sacubitril/valsartan on CTRCD
A retrospective case study described two anthracycline-related cardiomyopathy survivors with HFrEF who were treated with sacubitril/valsartan with success after poor responses to conventional evidence-based drug treatment (37). Both subjects exhibited fair recovery of NYHA functional class and normalization of NT-proBNP concentration as well as no re-hospitalization for heart failure (37) (Table 1 ). Canale et al. reported a case series of four patients with CTRCD and severe HFrEF (38). All patients were managed with sacubitril/valsartan with success while being combatting malignant ventricular arrhythmias by wearing an automatic defibrillator until heart function recovery (38) (Table 1 ).
In a pilot study, twenty-one patients with HFrEF and a history of histologically confirmed cancer received sacubitril/valsartan (39). Sacubitril/valsartan was well tolerated and effective over a median duration of 12 months. Even patients with long-term cardiotoxicity-related HFrEF could be titrated with ANRI to the target dose, giving rise to significant improvement in NYHA cardiac function grading and LVEF as assessed by echocardiography, as well as in their NT-proBNP levels (39) (Table 1 ). A multicenter registry study in six Spanish hospitals with cardio-oncology clinics followed up sixty-seven cancer survivors managed with sacubitril/valsartan (40). After a median duration of 4.6 [1; 11] months, sacubitril/valsartan was well-tolerated and improved cardiac functional and structural characteristics assessed by echocardiography, NT-proBNP concentration, and NYHA functional class in patients with HFrEF regardless of the achieved agent dose (40) (Table 1 ).
Renato et al. (41) reported two clinical cases of cardiotoxicity-related HFrEF where therapeutic action of sacubitril/valsartan against anthracycline cardiomyopathy was proven by the improvement of symptoms and echocardiographic parameters (Table 1 ). Ana et al. (42) evaluated the therapeutic effect of sacubitril/valsartan on LVEF and LV remodelling assessed by comprehensive multiparametric cardiac magnetic resonance (CMR) in ten consecutive patients with cardiotoxicity-related HFrEF. LV volumes decreased markedly and LVEF improved significantly after administration of sacubitril/valsartan. A corresponding marked decrease in NT-proBNP concentration and improvement in NYHA functional class were also observed (42). LV dysfunction within CTRCD is partly restorable, but this strongly dependeds on timely treatment with sacubitril/valsartan (42) (Table 1 ). Twenty-eight patients with breast cancer and refractory cardiotoxicity-related HFrEF were initiated with sacubitril/valsartan after poor responses to conventional evidence-based drug treatment (43). Twenty months after captopril or valsartan was replaced with ARNI, there was a significant improvement in NYHA cardiac function grade, six-minute walking distance, LVEF, LV diastolic function, LV end-diastolic diameter and mitral regurgitation assessed by echocardiography, as well as NT-proBNP levels, without drug reactions (43) (Table 1 ). Although this research has some defects, such as a limited sample and an inadequate description of past cancer history, it provides new evidence for improving the clinical management of patients with CTRCD.