Use of Sacubitril/Valsartan in a Chronic Heart Failure Patient with Reduced Ejection Fraction Accompany Dilated Cardiomyopathy and Myocardial Indensication: A Case Report

Rationale: Dilated cardiomyopathy (DCM) is a progressive cardiac disease characterized by ventricular dilation and contractile dysfunction and is the third most common cause of heart failure and the most common cause of heart transplantation. Heart failure (HF) and atrial brillation (AF) often coexist and share a mutually benecial relationship. The presence of atrial brillation increases the tendency for heart failure, which can worsen its severity and increase the risk of stroke. DCM (cid:0) AF and HF are causal to each other in pathophysiological view. However, how these pathogens translates upon acute decompensation heart failure(ADHF) is unknown. Control acute attack of chronic heart failure is the rst step of treatment. Case summary: Herein, we described a 68-year-old man with acute decompensated heart failure (ADHF) with severe DCM and atrial brillation who was treated with Sacubitril/Valsartan and had a reduced ejection fraction. The patient’s echocardiography features had a signicant improvement under taking Sacubitril/Valsartan. Sacubitril/Valsartan may act as an intermediary that balancing of the good and the bad neuroendocrine response. represents new strategy for of echocardiographic and positive


Introduction
Dilated cardiomyopathy is characterised by left ventricular dilation that is associated with systolic dysfunction, with diastolic dysfunction and impaired right ventricular function can develop, and has being a major problem that lead to HF ultimately. Patients on long-term treatment sometimes have acute decompensated heart failure. Other life-threatening risks include ventricular arrhythmia, atrioventricular block, syncope, and sudden death. The extremely high hospitalization rate and potential heart transplant requirements result in a huge cost burden [1] . The focus of DCM treatment is to improve cardiac e ciency and reduce mechanical stress. The treatment of arrhythmia and the prevention of sudden death are still the main contents of treatment.
Sacubitril/Valsartan (formerly LCZ696) is a class of rst-class angiotensin receptor blocking-neprilysin inhibitors (ARNI). It also inhibits the activation of RAAS by blocking angiotensin II type 1 receptor, and by inhibiting neprilysin (enzyme responsible for degradation) to enhance vasoactive peptides including NPs [2] . Based on the PARADIGM-HF randomized controlled trial, Sacubitril/Valsartan was approved by the US Food and Drug Administration and the European Medicines Agency in 2015 [3] . Subsequently, Sacubitril/Valsartan is recommended for the treatment of chronic heart failure with reduced ejection fraction. Despite the best treatment in accordance with international guidelines(2016 ESC guidelines [4] ,2017 ACC/AHA/HFSA guidelines update [5] ,2017CCS guidelines update [6] ,all as I class of recommendation), there are still symptoms. Indeed, with the support of recent research results and a huge clinical development project, this type of new drugs for the management of heart failure may lead to a change in the concept of heart failure treatment, from inhibiting RAAS and SNS to a more comprehensive target. To balance the neurohormonal disorders of heart failure [7] . We reported a case of an II-III New York Heart Association (NYHA) Class, stage D HFrEF in DCM's patient with myocardial indensi cation occurred despite optimal medical therapy and successfully treated with sacubitril/valsartan once reached persistent hemodynamic stabilization. In this case, we focus on the patient 's treatment process, clinical index, therapeutic effect and prognosis in the course of using Sacubitril/Valsartan.

Discussion
DCM is characterized by left ventricular dilation, which is related to systolic dysfunction, diastolic dysfunction and impaired right ventricular function may also occur. The treatment of DCM is mainly aimed at the treatment of heart failure symptoms, preventing disease progression and related complications, such as end-organ dysfunction, stroke, etc. Myocardial densi cation failure is a rare cardiomyopathy caused by arrest of normal embryogenesis of the endocardium and myocardium. The prognosis of DCM and myocardial are very different, early diagnosis and treatment is helpful to prolong the patients' life.
HFrEF due to DCM and myocardial indensi cation frequently complicates HFrEF. Speci c therapies for DCM-related cardiomyopathy have not offered an advantage in patients with DCM-HFrEF. Here, we report how the use of Sacubitril/Valsartan in a patient with DCM-related HFrEF-NYHA II to III class, has resulted in a signi cantly improvement in clinical status and prognosis (laboratoristic, echocardiographic, and quality of life; and 14-months survival free from ADHFrEF). Before adding Sacubitril/Valsartan, the patient presented recurrent ADHFrEF despite optimal medical therapy, and more frequent of outpatient visits than after taking this medicine.
Sacubitril/Valsartan has been shown to improve mortality and reduce hospitalizations in patients with HFrEF [13] . The effect of Sacubitril/Valsartan on LVEF and reverse remodeling parameters have not been previously described by Strongly evidences. Sacubitril/Valsartan's effects were con rmed by improvement of echocardiographic features (LVEF increase, LVESD decrease, LVEDD decrease, left ventricular mass index decrease), survival free from HF (about 1 to 2 years), and quality of life [14,15] . Furthermore, compared with enalapril (ACEI), Sacubitril/valsartan had a higher effect on ADHF (HF), lower cardiovascular complications mortality and hospital stay, similar safety, and adverse reactions (such as deterioration in renal function), hyperkalemia, symptomatic hypotension, and angioedema) [16] . The echocardiographic features of this patient indicate Sacubitril/Valsartan can reverse cardiac remodeling by reducing LVEDD, LVESD, LA, RVEDD, at the same time increasing LVEF and FS.
Serological testing has been widely applied to preliminary diagnose and prognostic evaluate HF. In patients with HF, activation of the neuro-hormonal axis and in ammatory markers would take place as the disease progresses. The activation of NT-proBNP, ANP, cGMP, ALD, and ET-1can be measured and could aid in prognostic assessments. The most speci c, sensibility and widely used biomarker is NT-proBNP. A rise in NT-proBNP is associated with reduced left ventricular systolic function, hypertrophy, raised lling pressures, myocardial ischaemia [17] , and has become prediction of high risk of death, need for inhospitalisation, or need for cardiac transplantation. Temporal evolution of NT-proBNP activity from administration-before to administration-after had been recorded at every follow-up time. This curve of NT-proBNP-Time re ect that Sacubitril/Valsartan could be a vital medicine in reducing NT-proBNP to a certain extent. ANP and BNP act via natriuretic peptide G protein-coupled transmembrane receptors activating cGMP as second messenger which, in turn, exerts natriuretic, diuretic and vasodilating action [18] . Some of the peptides substrate for neprylisin are known to play a role in HF, such as natriuretic peptides, angiotensin, endothelin, bradykinin, substance P, aldosterone, and arginine vasopressin. All these peptides have effects theoretically important in HF such as limiting in ammation, reducing smooth muscle contraction, neutrophil adhesion and vascular permeability both in experimental models and in humans [9] . Overall, these neuroendocrine systems interact extensively. Sacubitril/Valsartan may act as an intermediary that balancing of the good and the bad neuroendocrine response.
To our knowledge, myocardial indensi cation-related DCM has a poorly clinical prognosis, and causes many complications (such as ADHFrEF, arrhythmias, and systemic thromboembolism), early diagnosis and treatment is helpful to prolong the patients' life. The emergence of Sacubitril/Valsartan represents the advent of a new strategy for treating HFrEF. Its bene cial effects are related in part, at least, to an improvement of echocardiographic features and positive modulation of the neuroendocrine response to HF.
In conclusion, this patient bene ted from Sacubitril/Valsartan in a low dose by a short-term follow-up date (14 months). Next, more studies would be need to con rm the long-term effect and projected bene t of Sacubitril/Valsartan on heart failure caused by dilated cardiomyopathy.

Declarations
Ethics approval and consent to participate Not applicable. Due to the treatment of a single patient with approved pharmacotherapy, no ethics approval was obtained. All authors thank the patient for informed consent to this publication and the related images.

Consent for publication
The authors thank the patient for informed consent to this publication and the related information.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable requests.

Competing interests
The authors declare that they have no competing interests.