Effect Of Recombinant Human Brain Natriuretic Peptide On Cardiac Function In Patients With Heart Failure With Preserved Ejection Fraction

Objective: The purpose of this study is to assess the effect of recombinant human brain natriuretic peptide on cardiac function in patients suffered from heart failure with preserved ejection fraction.Methods: From June 2014 to December 2015,a total of 61 patients(34 males and 27 females,aging from 58 to 83,average 70.32 ± 6.76 years old)with heart failure with preserved ejection fraction of the cardiology department in the second hospital of Hebei medical university were enrolled into this study.Eligible patients were randomly assigned to receive recombinant human brain natriuretic peptide(rhBNP group)or nitroglycerin(NIT group)by means of random number table.Inclusion criteria: 1)Compliance with the diagnosis of heart failure with preserved ejection fraction;2)Compliance with cardiac functional grading of NYHA Ⅲ-Ⅳ or Killip Ⅱ~Ⅲ.3)Patients or family members of patients had signed surgical informed consent.Exclusion criteria: 1)Shock(systolic pressure was lower than 80mmHg;pulse pressure difference was lower than 20mmHg;slender pulse or couldn’t be touched;clammy limbs,positive reaction to compression on sternal skin,pale mucosa or cyanosis,urine volume was less than 30ml/h or anuresis;drop of systolic pressure from the original level was more than 30% in patients with original hypertension;abnormal consciousness.2)Heart failure with reduced ejection fraction.3)Pericardial disease,valvular heart disease,restricted or hypertrophic obstructive cardiomyopathy,acute myocarditis and non-cardiac conditions caused symptoms of heart failure.4)Severe hepatic and renal insufficiency.5)Allergic to rhBNP or nitroglycerin.6)Need mechanical ventilation.7)Existence of autoimmune disease,severe injury,hemorrhagic diseases,or tumor.8)Patients or family members refused to participate in this study.Exit criteria: 1)Death within 24 hours after admission,the clinical data was not completed.2)Urine volume was less than 100 ml per day,need bedside hemodialysis.Interventions: Patients in rhBNP group were given rhBNP slowly with the loading dose of 1.5μg/kg by intravenous injection,and then rhBNP was pumped at a speed of 0.0075 μg/kg·min.The dose was increased from 0.0075 μg/kg·min to 0.030 μg/kg·min according to patient’s symptoms until reached the maximum tolerated dose within 6h with which rhBNP was continuously intravenous pumped for 72 hours,then reduced and stopped gradually within 24 hours.Patients in NIT group were given Nitroglycerin continuously,which was pumped with the dose of 10ug/min initially.The dose was increased according to patient’s symptoms until reached the maximum tolerated dose within 6h with which rhBNP was continuously intravenous pumped for 72 hours,then reduced and stopped gradually within 24 hours.During the treatment all patients’ systolic blood pressure were not less than 90 mmHg.Other medications such as vasodilator,β-blockers,aspirin,clopidogrel,statins,Calcium channel blockers,ACEI/ARB,platelet glycoprotein IIb/IIIa receptor antagonist,anticoagulant drugs and so on were all used according to the current guidelines.Observation of indexes and treatment of statistic: After admission we recorded the basic clinical data of patients,including sex,age,weight,height,history of smoking,disease of history(hypertension,diabetes and hyperlipidemia),NYHA cardiac functional grading,Killip classification,and incidence and clinical medication.Record and compared the degree of dyspnea relief,respiratory rate,arterial partial pressure of oxygen,difference of output and intake in 24 hours,blood pressure,heart rate,value of NTproBNP and echocardiography examinations.Echocardiography examinations include: LVEF,E/e,and LAVI.At the same time,adverse reactions were observed during treatment such as allergies,hypotension,acute kidney damage and ventricular arrhythmias.We followed up the level of NT-proBNP,echocardiographic parameters for one month and major adverse cardiac events(MACEs)for three month.All statistic data were analyzed by SPSS20.0,it was considered statistical significance when P was lower than 0.05.Results:1 There was no significant difference between rhBNP group and NIT group in sex,age,weight,height,history of smoking,disease of history(hypertension,diabetes and hyperlipidemia),NYHA cardiac functional grading,Killip classification,clinical medication and incidence of disease(P >0.05).2 Dyspnea was improved significantly after 24 hours treatment in both groups compared with baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group(P<0.05).Breathing rate slowed down significantly compared with baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group(P<0.05).Oxygen partial pressure of arterial blood increased significantly compared with the baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group(P<0.05).The difference between output and intake in 24 hours increased significantly compared with the baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group(P<0.05).Systolic pressure decreased significantly compared with baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group after 24 hours treatment(P<0.05).However,there was no significant difference in systolic pressure between rhBNP group and NIT group after 72 hours treatment.Diastolic pressure decreased significantly compared with the baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group after 24 hours and 72 hours treatment(P<0.05).Heart rate declined obviously compared with the baseline(P<0.05),which in rhBNP group was more significantly than that in NIT group(P<0.05).3 The level of plasma NT-proBNP of both groups decreased significantly after treatment(P<0.05)in 72 hours and 1 week compared with baseline,which in rhBNP group decreased more significantly than that in NIT group(1038.91±222.70pg/ml vs.1205.47±299.43pg/ml,P=0.016),(753.42±130.11pg/ml vs.26.00±162.38pg/ml,P<0.001).However after 1 months of treatment there was no significant difference in plasma NT-proBNP levels between rhBNP group and NIT group(496.23±36.40pg/ml vs.510.66±35.22pg/ml,P=0.121).4 The value of E/e,in two groups improved significantly compared with the baseline(P<0.05),which in rhBNP group was more significant than that in NIT group at 1 week and 1 month(14.18±2.33 vs.16.47±2.82,P=0.001),(10.21±2.76 vs.13.24±1.26,P<0.001).The value of LAVI in two groups improved significantly compared with the baseline(P<0.05),which in rhBNP group was more significant than that in NIT group at 1 week and 1 month(38.51±3.71ml/m2 vs.42.28±4.56ml/m2,P=0.001),(37.54±2.02ml/m2 vs.39.08±2.08ml/m2,P=0.001).There was no significant different in both groups in value of LVEF compared with baseline after 1 week and 1 month treatment(P>0.05),and there was no significant different in value of LVEF between rhBNP group and NIT group at 1 week and 1 month(53.12±3.29% vs.54.32±3.49%,P=0.170),(53.58±3.25% vs.54.66±3.42%,P=0.209).5 Adverse reactions of two groups: There was no allergic reaction in patients of both groups.There was no renal insufficiency occurred or the original renal insufficiency aggravated in the two groups.There was one case in rhBNP group,while two cases in NIT group suffered from hypotension which did not occur again after adjusting the dose.There were six cases in NIT group occurred headache,compared with zero case in rhBNP group.The NIT group had higher incidence of headache than the rhBNP group(P <0.05).There were two cases in NIT group with ventricular arrhythmia(one with requent ventricular premature beat and another with paroxysmal ventricular tachycardia),compared with zero case in rhBNP group which did not occur after the addition of anti arrhythmia drugs.There was no significant different incidence of ventricular arrhythmia.There was no acute renal injury occurred in both groups.6 MACEs: In rhBNP group,there was one case of severe ventricular arrhythmia,compared with two cases in NIT group.There was no significant different incidence of severe ventricular arrhythmia.There was zero case in rhBNP group with heart failure deterioration compared with two cases in NIT group.NIT group had higher incidence of heart failure deterioration than the rhBNP group(P <0.05).There was no sudden cardiac death in both groups.Conclusions: Compared with nitroglycerin,rhBNP can more effectively improve clinical symptoms,cardiac function and left ventricular diastolic function of the patients who suffer from heart failure with preserved ejection fraction.