Effects Of Sacubitril/valsartan On The Right Ventricular Function In Patients With Left Heart Failure Complicated With Pulmonary Hypertension

Objective:To observe the effects of sacubitril/valsartan on the right ventricular function in patients with heart failure complicated with pulmonary hypertension by echocardiography,so as to provide broad theoretical basis for the clinical treatment of decompensated heart failure.Methods:1.Fifty-one patients with heart failure complicated with pulmonary hypertension,who were admitted to the Department of Cardiovascular Medicine,Affiliated Hospital of Qingdao University from September 2020 to March 2021,were chosen as the objects of the research.Patients were randomly divided into two groups,which included the ARB group(patients with valsartan,n=25)and the ARNI group(patients with sacubitril/valsartan,n=26).On top of the prescribed therapy based on guidelines,such as diuretics,digitalis,and vasodilators,the ARB group was administered valsartan 80 mg once a day and the ARNI group with sacubitril/valsartan 50 mg twice a day.Doses of ARB/ARNI were titrated gradually to target levels whenever possible.Both groups were treated continuously for 6 months.2.Clinical baseline data,including age,sex,smoking history,comorbidities,underlying heart failure diseases,and medication for heart failure,were collected through the electronic medical records.Echocardiography was performed before and after 6 months of treatment.Right ventricular systolic function was assessed by tricuspid annular plane systolic excursion(TAPSE),right ventricular fractional area change(RVFAC),and peak systolic myocardial velocity of tricuspid valve annulus(S’TV).Right ventricle-pulmonary artery(RV-PA)coupling was assessed by pulmonary artery systolic pressure(PASP)and the TAPSE/PASP ratio.The following parameters were also evaluated: left atrium diameter,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,and left ventricular ejection fraction.After 6 months,the individual drug target dose,the time to reach the target dose,and the incidence of adverse drug reactions and cardiovascular adverse events in the two groups were recorded.Results:1.A total of 51 patients were enrolled in the study,including 25 patients in the valsartan group and 26 patients in the sacubitril/valsartan group.The average age of valsartan group was(63.40 ± 8.64)years,including 14 males and 11 females.The average age of the sacubitril/valsartan group was(63.27 ± 6.44)years,including 16 males and 10 females.There were no significant differences in the history of smoking,concomitant diseases(atrial fibrillation,hypertension,diabetes),basic diseases of heart failure(dilated cardiomyopathy,ischemic cardiomyopathy)and drug use of heart failure(diuretics,digoxin,β-receptor antagonists,dapagliflozin)between the two groups(P > 0.05).2.Comparison of right ventricular function indexes between the two groups before and after treatment: The TAPSE,FAC and S ’indexes were not statistically significant between the two groups before treatment(P > 0.05).After 6 months of treatment,TAPSE and S ’in both group were increased with statistical significance(P < 0.05).The increase in the ARNI group was greater than that in the ARB group,with a statistical difference(P <0.05).FAC in the ARNI group increased from(32.60±5.76)% to(42.96±9.04)%,the difference was statistically significant(P < 0.05).And compared with the ARB group,the degree of increase was statistically significant(P < 0.05).3.Comparison of right ventricle-pulmonary artery coupling indexes between the two groups before and after treatment: Before treatment,there was no significant difference between the two groups in comparison of PASP,T/P ratio and LAD indicators(P>0.05).After 6 months of treatment,the PASP of patients in the ARNI group and the ARB group decreased significantly from(54.23 ± 8.84)mm Hg to(35.54 ± 7.63)mm Hg and(52.44 ±6.77)mm Hg to(41.16 ± 8.20)mm Hg.The differences were statistically significant(P <0.05).The T/P ratio of the patients in the ARNI group and the ARB group increased significantly from(0.32 ± 0.10)to(0.51 ± 0.12)and(0.30 ± 0.08)to(0.41 ± 0.10)before treatment,respectively,with a statistically significant difference(P<0.05).There was no significant difference in the decrease of LAD in the ARB group compared with before treatment(P>0.05).The decrease of PASP,the increase of T/P ratio and the decrease of LAD in the ARNI group were significantly higher than those in the ARB group(P<0.05).4.Comparison of left ventricular remodeling indexes between the two groups before and after treatment: Before treatment,there was no significant difference in LVEDD,LVESD and LVEF indexes between the two groups(P>0.05).After 6 months of treatment,LVEF in the ARNI group and the ARB group increased significantly from(37.81 ±8.07)% to(47.46 ± 8.66)% and(35.92 ± 6.56)% to(42.34±9.47)% before treatment,respectively,with a statistically significant difference(P<0.05).And the ARNI group was significantly higher than the ARB group(P<0.05).The reduction of LVEDD and LVESD in both groups was improved compared with that before treatment(P<0.05).The LVEDD and LVESD in the ARNI group decreased from(58.00 ± 6.85)mm to(47.00 ± 9.42)mm and(48.27 ± 9.38)mm to(39.15 ± 7.55)mm respectively,which were significantly higher than those in the ARB group(P<0.05).5.Comparison of individual target dose and the average time to reach target dose between the two groups after treatment: According to blood pressure,heart rate and individual tolerance,the drug dose was adjusted once every two weeks in outpatient follow-up until the recommended target dose or individual tolerance dose was reached.After 6 months,the initial dose of 80 mg Qd was unchanged in 6 patients in ARB group,the target dose of 19 patients was between 160 mg and 320 mg,and the target dose compliance rate was 76.00%.The average time to reach the individual target dose was(47.11±10.22)days.In the ARNI group,the initial dose of 4 patients with 50 mg Bid remained unchanged,the target dose of 22 patients was between 200 mg and 400 mg.The target dose compliance rate was 84.62%,and the average time to reach the target dose was(48.54±10.49)days.There was no significant difference in the rate of reaching target dose and the average time of reaching target dose between the two groups(P > 0.05).6.Comparison of adverse drug reactions and cardiovascular adverse events between the two groups after treatment: The doses of ARB and ARNI were adjusted at outpatient follow-up according to blood pressure,heart rate and individual tolerance until the target dose or individual maximum tolerated dose was reached.During treatment,no patients in both group experienced severe hypotension,angioneurotic oedema,hyperkalemia,impaired hepatic and renal function,and no cardiovascular deaths.In the comparison of the occurrence of cardiovascular adverse events,three patients(12.00%)were rehospitalized for heart failure in the ARB group and two patients(7.69%)was rehospitalized in the ARNI group,and the comparison of the cardiovascular adverse events rate between the two groups(12.00% vs.7.69%,P=0.963)was not statistically significant.Conclusion:For patients with left heart failure complicated with pulmonary hypertension,compared with valsartan,after six months of treatment with sacubitril/valsartan,left ventricular remodeling was more significantly reversed,pulmonary artery systolic pressure was more significantly reduced,and right ventricular systolic function was more significantly improved.