Effects Of TMZ(trimetazidine) Heart Failure With Preserved Ejection Fraction

Heart is the power center of human’s blood circulation as well as the organ that consumes most energy in human’s body. The systolic and diastolic of heart need energy. In order to get the necessary energy, the heart has to transform the chemical energy restored in glucose and fatty acid into chemical energy of interaction of actin and myosin in myofibril. Generally, 60%- 90% of the required energy for action of cardiac muscles comes from free fatty acids, the rest comes from carbohydrate. There is a mutual-feedback relation between the oxidative metabolism of fatty acids and that of glucose, the enhancement of oxidative metabolism of glucose will repress the oxidative metabolism of fatty acids, and vice versa. When the cardiac suffers ischemia, the cardiac muscle organizations will make a change on energy metabolism: when the ischemia is slight, there will be no obvious changes in oxidative metabolism of cardiac muscle; when the ischemia is mediate, the sugar yeast decomposition accelerates, the oxidative metabolism of fatty acids enhances and the oxidation of glucose will be repressed; when the ischemia is severe, the ATP produced by sugar yeast decomposition will become the only energy source of cardiac muscle cells. It can be seen that when cardiac muscle suffer mediate or severe ischemia, the oxidative of fatty acids enhance which leads to the accumulation of free fatty acids and the poisoning of cells, both of which will cause the injury or death of cardiac muscle cells. The main pathological changes of heart-failure is the reconstruction of ventricle and fibrosis of cardiac muscle. On the other hand, experiments show that the vitality of ATP enzyme will decrease 20%-30% in heart-failure. The decreasing of vitality of ATP enzyme will make hindrance of the utility of cardiac energy and further lead to weakening of cardiac muscle systolic. Another feature of cardiac muscle reconstruction is death of cardiac muscle cells, including necrosis andapoptosis. The death of cardiac muscle cells will cause fibrillation and hinder the cardiac systolic. Researches show that to optimize the metabolism of cardiac muscle is an effective approach to relieve the inchemia of cardiac muscle and improve the cardiac function. At present, many medicines are able to optimize the metabolism of cardiac muscle, and TMZ(trimetazidine) is one of them. When the cardiac muscle suffers inchemia, the trimetazidine can increase the synthesis efficiency of ATP and improve the symptoms of inchemia by stopping the oxidation of fatty acids of cardiac muscle cells and enhancing the oxidation of glucose. However, there are some controversies existing in the cure of heart-failure with inchemia. This thesis tries to explore the impact of TMZ on cardiac systolic by researching the clinic curative effect of TMZ on HFPEF.Objective: By observing the clinical curative effect of TMZ on heart-failure victim, to explore its impact on the cardiac functions of heart-failure victim with and without inchemia.Methods: Observing 100 cases of HFHEF victim who received hospitalization since August 2012 to November, 2013. Among them, 90 cases are with hypertension, 68 cases are with coronary heart disease and 18 cases are with diabetesⅡ. All victims conform to the diagnostic criteria of HFPEF set by ESC(European Society of Cardiology) in 2007 and the Consensus for HEPEF by Chinese specialties set in 2010. The criteria include:(1) age>60 years old;(2) performance of symptoms and signs of heart failure;(3) presence of normal or only mildly abnormal left ventricular systolic function( LVEF≥45%),LVEDVI<97 ml/m2;(4) echocardiographic evidence of diastolic dysfunction,E/E’≥8(5) with a history of NYHA class Ⅱ--Ⅳ.(6) NT-pro BNP > 220 pg/ml. The victims are classified into observation group with 50 cases and control group with the other 50 cases in random. Both the two groups receive normal basic treatment after entering hospital. Later the control group receive only normal basic treatment while the observation group take the TMZ three times a day, 20 mg per time for two weeks on the basis of normal basic treatment. Both the two groups will accept the measurement ofNT-pro BNP and ultrasonic cardiogram on the first day and two weeks later respectively. All the data adopt the SPSS 12.0 zip to make processing, with P less than 0.05 as obvious statistical difference.Results: 1 There was no significant difference between the treatment(TMZ group) and the control group in baseline data,such as age,sex,hypertension,diabetes,diabetes disease,smoking,drinking histories,atrial fibrillation and the blood pressure,heart rate,NYHA class,liver function,kidney function, the level of NT-pro BNP, echocardiographic parameters and the 6-minute walk test(6-MWT)( P >0.05)( table 1). 2 The impact of TMZ on NT-pro BNP The NT-pro BNP of observation group before treatment(TMZ group) and control group were(1366±316)pg/ml and(1407±321)pg/ml respectively, there was no significant difference between them(P >0.05). The NT-pro BNP of observation group after treatment and control group were(790±231)pg/ml and(842±261)pg/ml respectively,and there was no significant difference between them(P <0.05). 3 The impact of TMZ on echocardiographic parameters 3.1 The LVEDD of observation group before treatment(TMZ group) and control group were(46.96±3.35)mm and(45.96±3.25)mm, there was no significant difference between them(P >0.05); The LVEDD of observation group after treatment and control group were(41.89±2.78)mm and(42.98±2.56)mm, and there was no significant difference between them(P <0.05). 3.2 The LVEF of observation group before treatment(TMZ group) and control group were(63.01±3.69)mm and(62.71±2.51)mm, there was no significant difference between them(P >0.05); The LVEF of observation group after treatment and control group were(68.22±2.87)mm and(63.03±2.51)mm, and there was no significant difference between them(P <0.05). 3.3 The LVESD of observation group before treatment(TMZ group) and control group were(33.01±2.20)mm and(32.56±2.21)mm,and there was nosignificant difference between them(P >0.05); The LVESD of observation group after treatment had decreased comparing with that before treatment(P<0.05),but there was no significant difference between the two groups after treatment(30.22±2.01 mm vs.30.71±2.01 mm, P >0.05). 3.4 The LVM of observation group before treatment(TMZ group) and control group were(196.54±17.86)mm and(198.01±18.02)mm, and there was no significant difference between them(P >0.05); The LVM of observation group after treatment had decreased comparing with that before treatment(P <0.05),but there was no significant difference between the two groups after treatment(193.79±16.65 g vs.195.01±17.22 g, P >0.05). 4 The impact of TMZ on victim’s activity endurance After treatment the results of 6-MWT showed significantly improvement than before in the observation group(TMZ group)(345.8±12.7 m vs. 445.5±18.6 m,P<0.05),and there was significant difference between the two groups after treatment(445.5±18.6 m vs.399.2±17.8m,P <0.05). 5 The impact of TMZ on victim’s cardiac functions The number of victims with NYHA Ⅱin observation group(TMZ group) increased significantly after treatment, and there was significant difference between the before and after treatment(17 vs. 4, P <0.05). The number of victims with NYHA Ⅲand Ⅳdecreased significantly after treatment, and there was significant difference between the before and after treatment(33 vs. 46,P<0.05). In the comparison between observation group and control group, the number of victims with NYHA Ⅱincreased, and there was significant difference between the two groups(17 vs. 8,P <0.05), the number of victims with NYHA Ⅲand Ⅳdecreased, and there was significant difference between the two groups(33 vs. 42, P <0.05).Conclusion: TMZ Can improve the cardiac function、clinical symptoms and the exercise endurance in heart failure patients with preserved ejection fraction effectively.