Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of atrial natriuretic peptide (ANP) on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodeling in patients with first anterior acute myocardial infarction (AMI) after primary coronary angioplasty. BACKGROUND: The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide, a circulating hormone of cardiac origin, has vasodilatory and diuretic properties, and can inhibit the RAAS. METHODS: We studied 50 patients with first anterior AMI who were randomly assigned to receive ANP (group A) or isosorbide dinitrate (group B) before and after primary coronary angioplasty. The ANP or ISDN was continuously infused >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. The LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine scintigraphy after 3 weeks. RESULTS: After primary angioplasty, age, gender, risk factors, peak serum creatine phosphokinase concentration, recanalization time, and ES were similar in the 2 groups. However, in group A (n = 25), the TDS was significantly lower (34 +/- 8 vs. 41 +/- 8; p < 0.05), the H/M ratio was significantly higher (1.96 +/- 0.18 vs. 1.74 +/- 0.23; p < 0.05), and the WR was significantly lower (35 +/- 8% vs. 44 +/- 12%; p < 0.005) than in group B (n = 25). Moreover, the LVEDV and LVEF in group A were better than in group B (LVEDV: 85.5 +/- 28.5 ml vs. 106.3 +/- 39.4 ml [p < 0.05]; LVEF: 47.9 +/- 10.2% vs. 41.5 +/- 11.8% [p < 0.05]). CONCLUSIONS: Intravenous ANP improves CSNA and prevents LV remodeling in patients with first anterior AMI.     

螺内酯抑制急性前壁心肌梗死患者的左室重构

目的探讨急性前壁心肌梗死患者口服螺内酯对于左室重构的影响。方法将急性前壁心肌梗死患者随机分为两组。对照组30例,接受血管紧张素转换酶抑制剂、β-受体阻滞剂、抗血小板、调脂药物等常规处理。螺内酯组30例,在常规治疗基础上加用螺内酯（40mg,每日1次）。随访1年,并检测脑钠尿肽（BNP）及超声心动图以评价左室功能和左室容积。结果6和12月时螺内酯组血清BNP水平明显低于对照组[（355±74）ng/Lvs（418±77）ng/L,P<0.05和（316±72）ng/Lvs（389±67）ng/L,P<0.05],且12月时螺内酯组较对照组左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）明显缩小[LVEDD:（49±6）mmvs（53±5）mm,P<0.05;LVESD:（37±5）mmvs（40±4）mm,P<0.05]。结论螺内酯可抑制急性前壁心肌梗死患者左室重构。     

同型半胱氨酸、N-末端脑钠肽前体与急性心肌梗死后左心室重构的关系

目的 探讨急性心肌梗死（acute myocardical infarction,AMI）患者同型半胱氨酸（homocysteine,Hcy）、N-末端脑钠肽前体（N-terminal pro-brain natriuretic peptide,NT-proBNP）浓度对心肌梗死后左心室重构的预测价值及对AMI患者临床预后的影响.方法 选择2009年6月至2011年6月在广州市第一人民医院心内科住院并诊断为急性ST段抬高型心肌梗死（STEMI）的患者266例,根据入院后空腹Hcy浓度的三分位数间距将患者分为A组（Hcy＜15.6μmol/L）83例,B组（15.6～24.6 μmol/L）组93例和C组（Hcy＞24.6μmol/L）90例.测定患者入院时即刻NT-proBNP浓度,并于入院48 h内及半年后行超声心动图测定患者左心室舒张末期内径（LVEDd）、左心室舒张末期容积（LVEDV）,左心室收缩末期容积（LVESV）,左心室射血分数（LVEF）.动态追踪观察3组患者随访期间内（6个月）的主要心血管事件（MACE）的发生情况.结果 三组患者随Hcy浓度升高,NT-proBNP浓度升高,左心室舒张末期容积和左心室收缩末期容积显著增加,左心室射血分数降低（P＜0.05 or P＜0.01）.ST段抬高型心肌梗死患者Hcy与NT-proBNP浓度呈正相关（r=0.380,P＜0.05）.直接经皮冠状动脉介入治疗随访6个月,Kaplan-Meier生存分析发现三组患者累积无主要心血管事件生存率比较,差异有统计学意义（91.6％ vs.86.0％ vs.77.8％,Log rank=6.630,P=0.036）.多因素Logistic回归分析显示Hcy、NT-proBNP均是ST段抬高型心肌梗死患者近期主要心血管事件发生的独立预测因子.结论 AMI患者Hcy、NT-proBNP浓度与梗死后心室重构密切相关,Hcy、NT-proBNP对患者的近期预后具有预测意义.     

急性心肌梗死患者早期血浆脑钠素与左室重塑的关系

目的　探讨急性心肌梗死 (AMI)早期血浆脑钠素与左室重塑的关系。方法　 44例AMI患者分为依那普利组及常规治疗组 ,采用放射免疫法测定入院后 14d内血浆脑钠素水平 ;超声心动图测定同期及 3个月左室舒张末容积指数 (LVEDVI)、左室收缩末容积指数 (LVESVI)及左室射血分数 (LVEF)。结果　常规治疗组入院后即刻血浆脑钠素水平较健康对照组明显升高 (P <0 .0 1) ,5、14d较入院即刻进一步升高 (P <0 .0 5 )。AMI患者 5、14d血浆脑钠素水平与同期及 3个月LVEDVI、LVESVI正相关 (P <0 .0 5 ,0 .0 1)。与常规治疗组相比 ,依那普利组脑钠素与心室容积指数一致性下降。结论　AMI后早期血浆脑钠素升高与左室重塑密切相关。     

Dynamics of left ventricular remodeling in patients with acute myocardial infarction

Dynamics of structural and functional left ventricular parameters was investigated in 51 patients with acute anterior myocardial infarction by means of serial (on days 1, 2, 3, 5, 7, 10 and 21 of infarction) echocardiographical study. Increase of end-diastolic volume index relative to initial values became significant on 5th-7th days and continued to progress until 3rd week of infarction. Left ventricular cavity became dilated and attained more occurred shape predominantly at the account of increased transverse diameters. Abnormalities of left ventricular contractile and pump functions were most pronounced during first 3 days of the disease. Between 5th and 10th days improvement and stabilization of myocardial functional state took place accompanied by progression of left ventricular dilation and increase of its sphericity with lessening of degree of myocardial asynergy.     

Plasma C-reactive protein predicts left ventricular remodeling and function after a first acute anterior wall myocardial infarction treated with coronary angioplasty: comparison with brain natriuretic peptide

BACKGROUND: C-reactive protein (CRP) directly participates in the myocardial injury of acute myocardial infarction (MI). Although high plasma CRP levels in the acute phase strongly indicate a poor early clinical outcome of patients with MI, the impact of CRP levels on late left ventricular (LV) function and remodeling, which are closely associated with long-term prognosis, remains unknown. HYPOTHESIS: Acute plasma CRP levels may predict late LV function and remodeling after MI. METHODS: We prospectively studied 12 consecutive patients with a first acute anterior MI recanalized by angioplasty. We measured plasma CRP levels on Days 0, 1, 2, 3, 4, and 7, and calculated the area under the curve (AUC). We also measured plasma brain natriuretic peptide (BNP) levels on Day 3 as the referential indicator of LV dysfunction and late LV remodeling. Late LV indices were independently assessed on a left ventriculogram obtained at 5.3 months to estimate the extent of LV remodeling. RESULTS: Plasma CRP reached its peak at Day 2.8 (8.68+/-4.57 mg/dl). On linear regression analysis, the AUC of CRP (35.21+/-19.33 mg/dl x day) correlated positively with BNP (316.5+/-418.6 pg/ml) (r = 0.646, p = 0.023). The AUC of CRP, peak CRP, and BNP correlated significantly with late LV indices. Among these, the AUC of CRP showed the best correlation with end-diastolic volume index (r = 0.765, p = 0.004), end-systolic volume index (r = 0.907, p < 0.001), and ejection fraction (r = -0.862, p < 0.001). CONCLUSIONS: Patients with high plasma CRP levels may be at risk for late LV dysfunction and remodeling; theoretically, their long-term prognosis may be poor. Measuring plasma CRP levels may provide valuable information for long-term risk stratification after MI.     

中期因子对大鼠心肌梗死后心室重塑的保护作用

目的观察中期因子（MK）对大鼠急性心肌梗死（AMI）后心室重塑的影响。方法成年雄性Wistar大鼠48只,随机分为4组：空白对照组（Control组）、伪手术组（sham组）、梗死模型组（AMI组）和MK干预组（MK组）。结扎大鼠左冠状动脉前降支（LAD）,建立AMI动物模型。模型制备成功后,在环绕LAD周围注射MK为MK干预组。4周后,对大鼠行血流动力学指标检测,称重,计算全心体重指数;取组织制备标本,Masson染色鉴定胶原生成情况;免疫组化检测心肌微血管;TUNEL检测细胞凋亡数;Westernblot分析左心室内Bel-2蛋白、P—ERK1蛋白含量的表达。结果MK组大鼠心功能较AMI组得到明显的改善（P〈0．05）;全心体重指数较AMI组明显降低（3．788±0．630比4．725±0．610,P〈0．05）。sham组与Control组几乎无胶原形成,而AMI组与MK组有明显的胶原组织。在梗死及梗死周边区微血管数目MK组多于AMI组（30．662±1．794比15．275±0．389,P〈0．05）,心肌细胞凋亡率明显低于AMI组（27．2±3．2比47．8±4．5,P〈0．05）。MK组Bcl-2蛋白表达较AMI组增多（1．8748±1．0406比1．3637±0．2528,P〈0．05）,P—ERK1蛋白表达较AMI组增多（1．2751±0．6353比0．7862±0．5470,P〈0．05）。结论MK对大鼠心梗后心室重塑产生保护作用,其机制可能与MK上调了P—ERK1蛋白表达有关。     

Left atrial remodeling in acute anterior myocardial infarction

BACKGROUND: Our goal in this study was to examine the changes in the left atrial functions over a period of 3 months by using left atrial volume measurements in patients with anterior myocardial infarction (MI). METHODS AND RESULTS: Seventy-three patients with anterior MI who consulted our hospital in the first 12 hours starting from the onset of the chest pain and who exhibited ST elevation were enrolled in the study. The left atrial functions of the patients were evaluated by transthoracic echocardiography for a total number of four times; first at the time of the visit to the hospital, then in the first week, and then in the first and third months. Eight (10.95%) of the 73 patients included in the study died during the follow-up. The remaining 65 patients completed the 3-month study period. Of these 65 patients, primary percutaneous transluminal coronary angioplasty (PTCA) was performed for 24 (36.9%) patients and thrombolytic therapy was given to 13 (20%), whereas 28 (43.1%) patients were given only medical treatment. Left atrium (LA) maximum transverse diameter, LA maximum, minimum, and presystolic volume, LA active emptying volume and fraction were found to increase significantly in comparison to baseline detected for this parameter in the first and third months (P < 0.001). However, LA passive emptying volume and fraction was found to decrease significantly in comparison to baseline detected for this parameter in the first and third months (P < 0.001). CONCLUSIONS: An increase in the diameter, volume, and dimensions of LA during atrial remodeling was detected. LA passive emptying fraction was found to decrease, whereas atrial active emptying function was found to increase to compensate for this change.     

Clinicopathological study of left ventricular remodeling after first acute myocardial infarction

The morphological characteristics of post-infarction ventricular remodeling were determined by comparison of infarct location and histological changes of noninfarcted myocardium at autopsy. A total of 94 cases of first acute myocardial infarction with clinical courses of 0 to 37 days were studied. Hearts were sliced on the short axis at the level of 1/3 of the distance from the atrioventricular ring to the apex. Wall thicknesses of the infarcted and noninfarcted areas, and the endocardial and epicardial perimeter lengths of the left ventricle were measured. Myocyte diameter and number of myocytes in the noninfarcted area were measured. Infarcts were classified into 3 groups based on infarct location (51 anterior, 22 posterior, and 21 nontransmural circumferential) and each group was further divided according to the clinical course of less than 72 hours or longer. Fifty two patients died within 72 hours. Cardiac rupture was the most common cause of death in the anterior group. Patients in the posterior group chiefly died due to cardiogenic shock and in the circumferential group chiefly died to pump failure. According to the number of stenosed coronary arteries, cardiac rupture was the most common cause of death in single-vessel disease in both anterior and posterior groups (62.1% and 55.6%, respectively). In double-vessel disease, the most common cause of death in the anterior group was still cardiac rupture (50.0%). On the other hand, 50.0% of the posterior group died of cardiogenic shock in double-vessel disease. Patients with triple-vessel disease mainly died due to heart failure in all groups. Wall thickness of the infarcted myocardium was decreased in the anterior group after 72 hours (11.8 +/- 3.5 vs 7.8 +/- 2.5 mm). Endocardial perimeter length was increased in the anterior and circumferential groups (83.6 +/- 25.6 vs 116.3 +/- 29.5 mm, 75.2 +/- 12.0 vs 117.6 +/- 3.1 mm, respectively). Endocardial/epicardial perimeter length ratio increased with longer clinical course in the anterior group. No specific change in wall thickness or perimeter length was found in the posterior group. Noninfarcted wall thickness was preserved in both the anterior and posterior groups. Myocyte diameter and number of myocytes in the noninfarcted area showed no significant difference after 72 hours. The nature of ventricular remodeling differs with infarct location. Ventricular dilation occurred during the clinical course in the anterior group. The transmural and adjacent areas are more important than the remote noninfarcted area in post-infarction remodeling within this period.     

Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction

Background

The effects of physical training on ventricular remodeling after extensive anterior acute myocardial infarction (AMI) have not yet been defined. This randomized controlled study examines whether exercise aggravates left ventricular (LV) remodeling in patients with extensive anterior AMI.

Methods

Forty-eight consecutive patients with a first extensive anterior AMI and an LV ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3 days of onset were randomly allocated to a training group (n = 24) or a control group (n = 24). Exercise intensity was determined by the heart rate of each patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was performed, followed by a supervised exercise program at VT for 12 weeks. The LVG was reassessed after the exercise program. We then calculated the global LV volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and systolic expansion volume index (SEVI), a new parameter for measuring the infarction site expansion at the end-systolic phase.

Results

Both EDVI and ESVI significantly decreased in the control group from 1 to 4 months after onset (91.2 ± 26.1 to 83.3 ± 24.0 mL/m², P <.05; 52.4 ± 22.5 to 45.7 ± 18.8mL/m², P <.01, respectively), but not in the exercise group. The SEVI also significantly decreased in the control group from 1 to 4 months (33.1 ± 16.9 to 25.7 ± 13.9 mL/m², P <.05), but not in the training group (34.2 ± 12.9 to 36.5 ± 15.5 mL/m², P = not significant).

Conclusion

Exercise while healing in patients with extensive anterior AMI, even at the VT level, induces LV enlargement and thus might aggravate LV remodeling. Therefore, in these patients, clinicians should consider withholding exercise training for at least 8 weeks, versus the 3-week period used in this trial.     

Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction

Background

Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function.

Methods

Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26 weeks. The primary end point was changes in LVEF from baseline to 6 months as assessed by MRI.

Results

Our main findings were: (i) LVEF increased significantly from 38 ± 10 (mean ± SD) to 45 ± 13% after IVIg and from 42 ± 9 to 49 ± 12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo.

Conclusions

IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling.     

Preinfarction angina prevents left ventricular remodeling in patients treated with thrombolysis for myocardial infarction

BACKGROUND: It has been shown that preinfarction angina may have beneficial effects on infarct size and mortality. However, there are no studies that have serially assessed the impact of preinfarction angina on left ventricular (LV) function in a large series of patients. HYPOTHESIS: The study was undertaken to determine whether preinfarction angina (within 7 days before infarction) influences LV remodeling. METHODS: In all, 119 consecutive patients with acute myocardial infarction were serially evaluated by 2-dimensional echocardiography (on Days 1, 2, 3, and 7; at 3 and 6 weeks; and at 3, 6, and 12 months following infarction). Left ventricular volumes were determined using Simpson's biplane formula and normalized for body surface area. Wall motion score index and sphericity index were calculated for each study. Coronary angiography was performed before discharge. RESULTS: Preinfarction angina was detected in 39 of 119 patients. Initial echocardiographic and clinical data as well as the incidence of patent infarct-related artery and collaterals were similar for patients with and without preinfarction angina. In the subset of thrombolysed patients, patients with preinfarction angina showed decrease of LV end-diastolic and end-systolic volumes during the follow-up period (p = 0.033 and p = 0.001, respectively), and improvement of wall motion score index (p < 0.001) and ejection fraction occurred (p = 0.001), without changing of LV shape (p > 0.05); in addition, patients with preinfarction angina had smaller LV volumes and higher ejection fraction than did those without angina, from 3 weeks onward. These favorable effects were not detected in patients not treated with thrombolysis. CONCLUSIONS: These data indicate that preinfarction angina has an inhibiting effect on long-term LV remodeling in patients who underwent thrombolysis for first acute myocardial infarction. It appears that preinfarction angina has no impact on infarct size and early postinfarction LV function.     

小剂量螺内酯抑制急性前壁心肌梗死患者的左室重构

目的 探讨小剂量螺内酯对急性前壁心肌梗死患者血清脑利钠肽（BNP）水平和左室重构的影响.方法 选择急性前壁心肌梗死患者90例,在常规治疗基础上,随机分为3组：常规治疗组30例,接受转换酶抑制剂、β受体阻滞剂、抗血小板、调脂药物等常规处理;小剂量螺内酯组30例,在上述治疗基础上每日给予螺内酯20 mg;中剂量螺内酯组30例,在上述治疗基础上每日给予螺内酯40 mg.结果 6个月时小剂量螺内酯组、中剂量螺内酯组和常规治疗组左室射血分数显著升高（P＜0.05）.治疗后常规治疗组BNP水平显著下降（P＜0.05）,小剂量螺内酯组和中剂量螺内酯组BNP水平下降更显著（P＜0.01）;小剂量螺内酯组与中剂量螺内酯组比较差异无统计学意义.结论 小剂量螺内酯抑制急性前壁心肌梗死患者的左室重构,血清BNP水平下降.     

N-terminal pro-B-type natriuretic peptide and matrix metalloproteinases in early and late left ventricular remodeling after acute myocardial infarction

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a predictor of left ventricular remodeling. Matrix metalloproteinases (MMPs) contribute to collagen breakdown that is associated with ventricular remodeling after acute myocardial infarction (AMI). We assessed the association between circulating levels of NT-pro-BNP, MMP-2, and MMP-9 and their inhibitor (tissue inhibitor of metalloproteinase-1) early (24 and 72 hours) and late (7 and 30 days) after AMI in 108 patients who had ST-elevation AMI (90 men; mean age 60 years). Serum MMP-2 levels measured 24 and 72 hours after AMI were inversely associated with NT-pro-BNP levels, whereas MMP-9 serum levels were positively related. During late-stage remodeling after AMI, circulating concentrations of tissue inhibitor of metalloproteinase-1 were independently associated with NT-pro-BNP levels 7 and 30 days after AMI. This study shows that, in patients who have ST-elevation AMI, circulating levels of NT-pro-BNP are associated with MMPs in a species-specific and time-dependent manner.     

Usefulness of plasma brain natriuretic peptide concentration for predicting subsequent left ventricular remodeling after coronary angioplasty in patients with acute myocardial infarction

To determine the relation between plasma brain natriuretic peptide (BNP) and remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a first anterior wall acute myocardial infarction with a patent IRA at 1 month were studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was patent in 89 patients (patent IRA). The 2 groups did not differ with respect to clinical characteristics, hemodynamic variables, and left ventricular function at 1 month, except for left ventricular end-diastolic and systolic volumes, which were significantly greater in the reoccluded IRA group. Plasma BNP concentration in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA 152 +/- 162 vs 44 +/- 58 pg/ml, p <0.05). The increase in left ventricular volume from 1 to 6 months was significantly correlated with plasma BNP concentration at 1 month in the patent IRA group (r = 0.314, p < 0.01) and the reoccluded group (r = 0.634, p < 0.01). Linear regression analysis showed that the correlation between the 2 parameters in the 2 groups was similar. Based on stepwise multivariate linear regression analysis, only plasma BNP concentration was significantly correlated with the increase in left ventricular volume from 1 to 6 months in the 2 groups. In conclusion, these results suggest that plasma BNP concentration predicts left ventricular dilation independently of IRA patency.