The Effect Of Sacubitril/Valsartan On Cardiac Remodeling In Maintenance Hemodialysis Patients With HFpEF

BackgroundMore than 50%of maintenance hemodialysis(MHD)patients have Cardiovascular Disease(CVD),which is the main cause of death in MHD patients.Chronic pressure overload and volume overload,and RAAS activation,oxidative stress,sympathetic nervous system activation,renal anemia,chronic inflammatory stimulation,bone and mineral metabolism axis,nitric oxide metabolism and the increase of endogenous cardiac glycoside concentration and other factors are all important causes of CVD in MHD patients.In addition,and hemodialysis(HD)itself will also cause myocardial injury.Left ventricular(LV)adapts to the increased pressure load,volume overload and myocardial injury by changing the mass(hypertrophy)or ventricular volume(dilation),which leading to the occurrence of cardiac remodeling.In MHD patients,changes in cardiac structure and function are often accompanied by HFpEF,which is a common CV complication.At present,in addition to the management of water load and the control of hypertension,there are relatively few effective treatments for MHD combined with HFpEF.Sacubitril/valsartan,an angiotensin receptor-neprilysin inhibitor(ARNI),including angiotensin Ⅱ type 1 receptor antagonist and Neprilysin inhibitor.It has the effects of relaxing blood vessels,increasing urinary sodium excretion,reducing blood pressure,reversing cardiac remodeling and supporting cardiomyocyte survival.Recommended for HFrEF patients in clinical practice guidelines can significantly improve HF symptoms and reduce the risk of HF hospitalization and cardiovascular death.ARNI can provide greater protection of target organs,including heart,blood vessels and kidney.The preliminary data of PROVE-HF and EVALUATE-HF showed that ARNI had some improvement in biomarkers and echocardiographic parameters of cardiac remodeling in patients with HFrEF.Animal studies have also shown that ARNI can effectively improve myocardial hypertrophy and fibrosis and reduce the markers of cardiac oxidative stress.At present,many studies use ARNI for various diseases,such as HFrEF,HFpEF,hypertension,CKD and pulmonary hypertension,these studies usually excluded patients with MHD.ARNI has great potential in reversing cardiac remodeling and the treatment of HF.At present,the research on the application of ARNI in MHD patients is limited,and the effect of ARNI on cardiac remodeling in MHD patients with HFpEF is unclear.ObjectiveOur study used the method of non-randomized controlled study to evaluate the effect of ARNI on cardiac remodeling in MHD patients with HFpEF by analyzing the changes of NT-proBNP and echocardiographic parameters at baseline and follow-up in ARNI group and routine treatment group,so as to provide reference for the treatment of cardiac remodeling in MHD patients with HFpEF.Materials and Method1.ParticipantsMaintenance hemodialysis patients were collected in the blood purification center of the First Affliated Hospital of Zhengzhou University from August 2020 to July 2021.Inclusion criteria:(1)age of hemodialysis≥3 months;(2)age≥18 years,≤80 years;(3)Signed informed consent;(4)Diastolic heart failure with preserved ejection fraction.(The patients had symptoms and signs of heart failure,LVEF≥50%and NT-proBNP>1200ng/L at baseline,and at least one of the following is met:(1.Abnormal cardiac structure:Left atrial volume index>34 ml/m2;left ventricular hypertrophy(LVMI≥115g/m2 in men and≥95g/m2 in women);2.Abnormal cardiac diastolic function:E/e’≥13;e ’mean value(ventricular septum and free wall)<9 cm/s).Exclusion criteria:(1)Complicated with severe infection,pulmonary embolism,Malignant tumor,etc;(2)Patients with severe valvular disease,congenital heart disease and cardiac resynchronization therapy;(3)Patients whose clinical data is incomplete.2.Baseline data of patients were collected:such as age,gender,history of hypertension,age of hemodialysis,primary disease,history of Diabetes,use of βreceptor blockers and calcium channel blockers,etc.3.The indexes of echocardiography,dry weight,blood pressure,the index of dialysis adequacy Kt/V and laboratory examination were collected at baseline and follow-up.(1)After hemodialysis,the same echocardiographist in our hospital collected LVEF,LVEDD,LVEDV,E peak,e’,LVPWD,IVSD,LAD and other cardiac indexes,LVM and LVMI were calculated by Devereux formula.(2)After hemodialysis,dry weight and excess water in the body are measured by bioelectrical impedance method,and calculate BMI and BSA.(3)The blood routine,blood biochemistry,NT-proBNP and other indexes of fasting venous blood in the morning were collected before hemodialysis.(4)Blood Pressure(BP)before hemodialysis(BP before HD),blood pressure during hemodialysis(BP during HD)and blood pressure after hemodialysis(BP after HD)were collected at baseline and follow-up.4.During the follow-up,the incidence of hypotension,hypoglycemia,nausea,vomiting and arrhythmia during HD were collected.5.Patients were divided into ARNI treatment group and other routine treatment groups by non-randomized controlled study.ARNI group took 100mg/twice a day on the basis of the original treatment,and stopped ACEI/ARB at the same time.The routine treatment group continued the original treatment(ACEI/ARB,β Receptor Blockers,etc.).6.The changes of NT-proBNP,echocardiographic parameters and blood pressure were analyzed by Statistical methods between the two groups at baseline and follow-up,so as to observe whether ARNI can effectively improve cardiac remodeling in MHD patients with HFpEF.Results(1)A total of 37 MHD patients were included in this study,24 males(64.9%)and 13 females(35.1%),with an average age of(49.89 ± 11.90)years.There were 16 patients in ARNI group,with a median follow-up time of 15(8-20)months,and 21 patients in routine treatment group,with a median follow-up time of 15(14-17)months.There was no statistical difference in age,height,dry weight,excess water in the body,Kt/V,gender,blood routine,history of hypertension,history of diabetes,age of hemodialysis,history of coronary heart disease,LVEF,the levels of NT-proBNP and so on between the two groups at the baseline(P>0.05).Compared with the routine treatment groups,LVEDD,LVESD,LVMI,LAD LVPWD,LVEDV,LVESV were higher in ARNI group(P<0.05).(2)Blood Pressure(BP):There was no significant difference groups in BP between the two before during and after HD at baseline(P>0.05).SBP before and SBP during HD in ARNI group was significantly lower than that in routine treatment group at follow-up(P<0.05).Compared with baseline,SBP before HD,DBP before HD,SBP in HD,SBP after HD and DBP after HD decreased significantly in ARNI group at follow-up(P<0.05).(3)Blood routine,blood biochemistry,venous blood potassium,dry weight,excess water in the body,Kt/V,and the level of NT-proBNP,E/e’,LVMI,LVEDD,LVEDV,LAD,IVSD,LVPWD and other indexes had no statistical significance compared with baseline in the routine treatment group.(P>0.05)(4)At follow-up,the level of NT-proBNP,LVEDD LVMI,LVEDV,LVESV and LVSV in ARNI group were significantly lower than those at baseline(P<0.05).E/e’,E/A,e ’,IVSD,LVPWD,right ventricular diameter,pulmonary artery ring diameter,ascending aorta ring diameter,pulmonary artery pressure,LAD and other echocardiographic parameters,dry weight,excess water in the body,Kt/V,blood routine,blood biochemistry,venous blood potassium and other electrolyte indexes also had no significant difference(P>0.05).(5)The analysis of the difference of cardiac indexes between the two groups at baseline and follow-up showed that the decrease of LVMI,LVEDV,LVEDD and NT-proBNP in the ARNI group were greater than those in the routine treatment group(P<0.05),and the improvement of cardiac indexes in ARNI group was significantly higher than that in routine treatment group.(6)In ARNI group,5(31.25%)patients appeared hypotension,1(6.25%)appeared arrhythmia and 1(6.25%)appeared muscle spasm during HD.In the routine treatment group,8 patients(38.10%)appeared hypotension,1 patient(4.76%)appeared muscle spasm,1 patient(4.76%)appeared hypoglycemia and 1 patient(4.76%)appeared nausea and vomiting during HD.There was no signi ficant difference in the incidence of hypotension,hypoglycemia,muscle spasm,arrhythmia,nausea and vomiting between the two groups.ConclusionIn MHD patients with HFpEF,ARNI can effectively reduce NT-proBNP level,blood pressure and echocardiographic parameters such as LVMI,LVEDD,LVEDV and LVESV.Therefore,ARNI can be recommended to reverse cardiac remodeling and improve heart failure in MHD patients with HFpEF.