The Phasic Change Of Left Ventricular Aneurysm Formation And The Effect Of PCI Combined With RhBNP On Left Ventricular Remodeling In AMI Patients

The expansion of ventricle after acute myocardial infarction (AMI) is one of the initial factors for the development of ventricular aneurysm . The early ventricular expansion mainly appeared in the region dominated by the infarction-related artery (IRA), if IRA is not opened in time, the infarction and non-infarction zones might have asynchronous motion, which might lead to the formation of acute Left ventricular aneurysm (ALVA). ALVA will aggravate stretch load to the myocardium at infarction margin, resulting in the progressive left ventricular remodeling, inducing or aggravating myocardial ischemia, deteriorating LVA and heart failure, and directly increasing the incidence of major adverse cardiac events (MACE). While AVA might occur at the early stage of AMI, the present researches were mainly focused on chronic LVA, which was clinically diagnosed for sustaining ST elevation lasting more than half a month, when granulation tissue grew into the infarction region to form scar tissue and anatomical LVA came into being, while the occurrence and evolution process of AVA within 72 hours after AMI has not been clear. Related researches indicated that mortality in AMI patients was the highest in those that occurred LVA within 48 hours after AMI. The mortality in patients with LVA was 6 times higher than that without LVA even if they had the similar LVEF. So it is most important to early diagnose LVA to intensify the reversing left ventricular remodeling treatment and decrease the mortality incidence.There was no detail report about the exact time when the earliest LVA occurred. Continuous ultrasound cardiogram detected that the left ventricle cavity begins to enlarge just 3 hours after AMI. Catheter left ventriculography(LVG)is a useful method for the morphological and hemodynamical diagnosis of LVA, which can be used to intuitively observe the changes of left ventricle's shape, structure, diastolic and systolic function. While brain or B-type natriuretic peptide (BNP ) is a member of the family of genetically distinct natriuretic peptides synthesized and released by cardiomyocytes in response to the overload of stress and volume, the level of BNP was positively related to volume and/or pressure load, which plays an important role in the protective compensate mechanism that adjusts the circulating dynamic volume and pressure. Brain natriuretic peptide (BNP) is synthesized and released by the stimulation of the ischemia of myocardium, overload of ventricular wall tension and pressure after AMI. The level of BNP was related to the intraventricular pressure, infarction area, the degree of heart failure. So BNP is a new biochemical marker to reflect progressive ventricular remodeling after AMI. But until now, the relationship between the plasma level of BNP and the process of left ventricular aneurysm formation was still unclear. In our study, the plasma BNP levels measured at different time after AMI and the location of infarction identified by LVG, were used to analyze the changes of LV function and remodeling characteristic after AMI and investigate the change of plasma BNP level after AMI, so that to find out the relationship between the plasma BNP level and the formation and progress of LVA in the term of neuroendocrine, as well to probe the significance of plasma peak level of BNP in the diagnosis of ventricular aneurysm. Furthermore, although percutaneous coronary intervention (PCI) is a common way to treat AMI, whether PCI can change or reverse the formation of LVA is still a question, and the report about the long term follow-up for this was rare. So the time sequence of the LVA formation in large scale of consecutive AMI patients and the influence of PCI at different time after AMI on the change of systolic synchrony were evaluated by LVG and phase analysis (PA) of ERNA respectively in our study.On other hand, in recent years, with the authorization of BNP in the way of diagnosis and assessment of ACS/AMI and the prognosis of heart failure, the clinical application of BNP has achieved great progress, the safety and effect of recombinant human brain natriuretic peptide (rhBNP) had also been proved in the treatment of acute decompensated heart failure (ADHF) by some clinical trails (include the ADHF resulted by acute anterior myocardial infarction). But its influence on the LV remodeling was still unclear. In our study, the influence of PCI combined with rhBNP on heart function and LV remodeling in AMI-LVA patients with HF were investigated through the LVG and equilibrium radionuclide angiography (ERNA).The contents and results of the study were as follows:PartⅠA study on the the phasic change of LVA formation in AMIObjective: This study was to evaluate the relationship between BNP peak level and the formation of LVA through the catheter method LVG in consecutive AMI patients, which can be used to analyse the phasic change of LVA formation , detect the risk factors that influence the formation of LVA and contrast the phasic process in changes of left ventricle's volume, pressure and configuration after AMI.Method: Total of 678 consecutive AMI patients (male,563cases, mean age 58±11yrs) admitted in our department from June 2004 to June 2008 were enrolled into this study. All patients were divided into four groups according to the duration of LVG to acute myocardial infarction attack: group A: (<3 hours), group B: (3-6hours), group C (6-24hours) and group D (24-72hours). All the AMI patients were performed coronary angiography (CAG) and PCI, the parameters of left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), left ventricular end diastolic pressure (LVEDP) and left ventricular wall motion score (LVWMS) were measured by LVG. The LVA was identified by LVG. And all the patients were divided into two groups (LVA group and non-LVA group) according to left ventricular wall motion. The clinical data and angiographical data of the patients were recorded. The two group patients'disease history, symptom and coronary CAG data were compared with univariate analysis and multivariate regression. Plasma BNP level was monitored at different time after AMI. The incidence of major adverse cardiac events (MACE) during in-hospital, including re-infarction, angina post AMI, congestive heart failure, malignent arrhythmia and death were recorded.Result:①There was no significant difference between the four groups in clinical characteristics such as age, sex and risk factors (including hypertension, diabetes mellitus, hyperlipidemia and smoking history). Coronary angiography showed that the occlusion site of infarction related artery (IRA), the multivessle lesion rate and the stenosis degree of the lesions were no significant difference among the four groups (P >0.05).②Cumulated incidence of LVA: 10% within 3 hours, 15.5% within 6 hours, 23.3% within 24 hours, 30.38% within 72 hours. The values of LVEDVI and WMS in group A, B and C were obvious lower, while the value of LVEF was obvious higher than that in group D. In group A, the value of LVESVI was also obvious lower than that in group D and the values of LVEDVI and WMS were lowered than those in group C. There was no significant difference of above parameters between group B and C.③Univariate significance analysis of 18 parameters in LVA group and non-LVA group: age, hypertension, angina history pre-AMI, first AMI history, anterior myocardial infarction, single vascular lesion (LAD or LCX), collateral circulation, occlusion site of IRA, time for occlusion of IRA were the risk factors for the formation of LVA after AMI. Logistic multivariate regression analysis indicated that anterior myocardial infarction, occlusion position of IRA, first AMI history, time from attack of AMI were the independent risk factors for the formation of LVA after AMI.④The value of LVEF in LVA group was significantly lowered (45.7±16.1 % vs 49.0±18.2%,P <0.05), while the values of LVEDVI, LVESVI and LVEDP were all obviously higher (113.2±25.1 ml/m~2 vs 104.1±26.3 ml/m~2, 63.2±35.1 ml/m~2 vs 54.6±27.2 ml/m~2, 18.8±3.2 mmHg vs 16.1±3.2 mmHg, P all<0.05), than those in non-LVA group. The disorder of left ventricular wall motion was obvious, and the LVWMS was obvious higher(7.7±2.9 vs 6.8±2.4,P <0.05), in LVA group than that in non-LVA group. ⑤The plasma concentrations of BNP in LVA group were obvious higher than that in non-LVA group 18 hours, the fifth day and 24th week after AMI (592.2±145.8 pg/ml vs 374.3±152.2 pg/ml, 378.2±139.7 pg/ml vs 178.3±31.7 pg/ml,106.4±28.4 pg/ml vs 64.2±22.9 pg/ml, P all<0.05).The peak value of plasma concentration of BNP was significantly higher (592.2±145.8 pg/ml vs 384.3±152.2 pg/ml,P<0.05), and the time for reaching peak value of plasma concentration of BNP was much shorter(17.2±2.9h vs 19.1±2.8h,P<0.01)in LVA group than that in non-LVA group. 6.The incidence of angina post AMI, re-infarction, mortality in hospital was obvious higher in LVA group than that in non-LVA group (43/206 vs 42/472,24/206 vs 14/472,16/206 vs 9/472,P all <0.05).Conclusion: The formation of LVA might occur in the early stage of AMI, the incidence of which was 10% within 3 hours after AMI, and the cumulated incidence of it was as high as 30% within 72 hours. The formation of LVA was influenced by a lot of factors. Anterior AMI, total or subtotal occlusion of the proximal and middle segment in LAD, occlusion time of IRA were its independent risk factors. The excess secretion of neuroendocrine hormone BNP played a role in the formation process of LVA. The heart function was obviously damaged and in-hospital mortality incidence was significantly increased in AMI patients with LVA.PartⅡEffect of percutaneous coronary intervention at different time on ventricular aneurysm formation and systolic synchrony in patients with acute myocardial infarctionObjective: This study was to evaluate the time sequence of the formation of LVA through left ventriculography(LVG) in large scale of consecutive AMI patients and assess the effect of PCI at different time after AMI on the LVA formation and its influence on systolic synchrony. The level of BNP was also measured to investigate its relation with LVA.Methods: From Jan 2004 to Dec 2006, a total of 326 consecutive patients of anterior AMI with LVA were enrolled into this study. LVA was diagnosed by LVG. All patients were divided into 4 groups according to the time of onset to balloon: group A (<3h), group B (3-6h), group C (6-12h) and group D (>1week). At baseline and 6 months after AMI, the parameters of left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), left ventricular end diastolic pressure (LVEDP) and left ventricular wall motion score (LVWMS) were measured by LVG. The paradox volume (PV) image of ventricle movement on the dynamic cine as well as the parameters of left ventricular systolic function (LVSF), left ventricular diastolic function (LVDF) and left ventricular systolic synchrony (LVSS) were measured by ERNA at 1 week and 6 months after AMI. Plasma BNP was measured 18 hours, 5 days and 24 weeks after AMI. The major adverse cardiac events (MACE) were recorded up to 3 years.Results:①The baseline LVG showed that the LVESVI, LVEDVI, WMS, LVEDP were lower, while LVEF was increased, in group A than that in other groups (P<0.05, respectively). At 6 months after AMI, the LVESVI, LVEDVI, LVEDP and LVWMS in the four groups were decreased, while LVEF was increased, than that at baseline. Those parameters in group A were changed most obviously (P<0.05, respectively).②At 6 months post AMI, LVEF, PER and PFR in group A were increased, while TPER, PS and FWHM were decreased than those in group D (P<0.05, respectively).③At 6th month post AMI, the cases with disappearance on the paradox volume in group A were obviously higher than that in group B, C, and D, and the PVI in group A was lower than that in group B, C, and D (P<0.05, respectively).④18 hours, 5 days and 24 weeks after AMI, the values of BNP in group D were higher than those in group A, B and C. There was no difference between group B and C (P<0.05, respectively).⑤Within the 3 years follow-up, the incidence of angina post-AMI and mortality in group A, B, and C was significantly lower than those in group D (P<0.05, respectively).Conclusions: The LVA can emerge shortly after AMI. The early, fully and permanently patency of infarction-related artery (IRA) can effectively inhibit the left ventricular remodeling process, prevent LVA formation, and improve LV function and prognosis.PartⅢClinical effects of percutaneous coronary intervention combined with intravenous recombinant human brain natriuretic peptide on acute myocardial infarction patients with left ventricular aneurysmObjective To evaluate the influence of PCI combined with rhBNP on ventricular remodeling and heart function in acute myocardial infarction patients with left ventricular aneurysm (AMI-LVA) through invasive hemodynamic monitoring, ultrasonic cardiogram and equilibrium radionuclide ventriculography (ERNA).Methods Total of 46 patients admitted in our hospital within 24 hours after AMI from June 2007 to June 2008 were randmized into two groups after PCI: group P-B (PCI combined with rhBNP, n=24) and group B (PCI and routine contrast treatment group, n=22). All the patients were underwent emergency PCI, and group A combined with rhBNP treatment: (1.5μg/kg bolus intravenous injection last for 90s with the same velocity followed by 0.0075-0.015μg/kg/min for the following 72 hours). Before, during and after the rhBNP infusion, the heart rate, systolic pressure, LVEDP and oxygen saturation were recorded. Two dimension echocardiography was used to measure the index of left ventricular end-diastolic volume (LVEDVI), the index of left ventricular end-systolic volume (LVESVI), the left ventricular ejection fraction (LVEF), the index of left ventricular mass (LVMI), the movement index of infarcted regional wall (RWMI) before. 1 week and 24 weeks after the administration of rhBNP. And 1 week and 24 weeks after the administration of rhBNP, the ventricular systolic synchrony parameters, that is phase shift (PS),full width at half maximum (FWHM) and peak phase standard deviation (PSD) were evaluated by ERNA. The changes of plasma BNP level were recorded before and 7 days after the administration of rhBNP The major adverse cardiac events (MACE) were followed up for 6 months.Results:①There was no significant difference between the two groups in clinical characteristics such as age, sex and risk factors. The peak level of CKMB was significantly lower in group P-B than that in group P-C (233.6±35.3 IU/L vs 288.5±34.6 IU/L,P<0.05).②After the administration of rhBNP, LVEDP was decreased and oxygen saturation was increased in both groups than in the baseline, and in group P-B, the extent was significantly higher than that in group B (4.6±1.1 mmHg vs 2.0±0.9 mmHg,5.5±1.2 % vs 2.3±1.2%, P all<0.05, respectively).③The value of LVEF in group P-B was higher than that in group P-C 1 week after treatment, while no signifcant difference between the two group 24 weeks. The values of LVESVI and LVEDVI in the two groups were both obviously decreased compared with those of baseline, which were more significant in group P-B than that in group P-C at each of the same time point. The values of LVWMI 1 week and 24 weeks after treatment were all obviously lowered compared with that of baseline of each group, and the value of LVWMI 24 weeks after treatment in group P-B was much lower than that in group P-C. The values of LVMI 24 weeks after treatment in group P-B were all significantly decreased in both of the two groups compared with that of baseline, which were decreased more in group P-B than that in group P-C, while there was no significant change 1 week after treatment in both of the two groups.④The values of PS, FWHM and PSD were no significant difference between the 2 groups 1 week after treatment, which were significantly lowered 24 weeks after treatment compared with that of 1week after treatment in both of the 2 groups. The values of PS, FWHM 24 weeks after treatment in group P-B were significantly decreased than that in group P-C.⑤The plasma levels BNP 7 days after PCI were both decreased significantly in both of the two groups (group P-B: 560.5±144.6 pg/ml vs 270.2±95.8 pg/ml, group P-C: 550.2±124.5 pg/ml vs 398.1±91.7 pg/ml, P all< 0.05), which were more significant in group P-B than that in group P-C.⑥The incidence of angina post-AMI, re-myocardial infarction, mortality and other major adverse complications(main organs bleeding) were no significant difference between group P-B and group P-C (20.8% vs 27.3%,8.3% vs 13.6%, 4.2 % vs 13.6%,12.5% vs 18.2%,P all >0.05).Conclusion: PCI combined with transvenous injection of rhBNP based on other routine treatments can further improve the left ventricular function, inhibit the remodeling of left ventricle, enhance the ventricular systolic synchrony and offer better prognosis of the patients.