Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction.

The left ventricle progressively dilates in some patients after acute myocardial infarction (AMI). Both systolic and diastolic left ventricular (LV) dysfunction can be of significance in the development of heart failure. Captopril has been shown to prevent dilatation, but the effect on LV diastolic function is unknown. In a placebo-controlled double-blind parallel study, 58 AMI patients with heart failure or low ejection fraction, or both, were consecutively randomized at day 7 to either placebo or captopril (25 mg twice daily). No differences were present between the groups at baseline. Fifty-three patients completed the 6-month study period. Both LV diastolic and systolic volume indexes increased significantly in the placebo group (17 and 14%, respectively); in the captopril group there was no change in LV diastolic volume index, but a 13% reduction in LV systolic volume index. Ejection fraction increased significantly in the captopril group. The peak flow velocities of the early and atrial filling phases were measured, and the ratio between the velocities was calculated. A significant reduction was observed during the study period in early peak flow velocity (65 to 52 cm/s) and in the ratio between early and atrial peak flow velocity (1.3 to 0.8) in the placebo group (p less than 0.05), but no significant changes occurred in the captopril group. No correlation was found between dilatation of the left ventricle and reduction in early peak flow velocity or the ratio between early and atrial peak flow velocity. In conclusion, captopril prevented LV dilatation, improved ejection fraction and prevented LV diastolic dysfunction in AMI patients with early signs of LV systolic dysfunction.     

不同剂量沙库巴曲缬沙坦对心肌梗死后心室重构的疗效及安全性评价

目的]观察急性心肌梗死(AMI)患者治疗前后心室重构相关指标的变化及药物不良反应情况,评价不同剂量沙库巴曲缬沙坦治疗AMI后心力衰竭患者的疗效及安全性。 [方法]选取2018年3月—2022年3月的174例急性ST段抬高型心肌梗死(STEMI)合并左心室射血分数(LVEF)＜50%的患者按随机分配接受最大耐受剂量的沙库巴曲缬沙坦(滴定至200 mg或最大耐受剂量,Bid,n＝80)或低剂量沙库巴曲缬沙坦(50 mg,Bid,n＝94)治疗,同时接受常规治疗。评价患者从基线检查(治疗前)至出院后12个月的血清氨基末端脑钠肽前体(NT-proBNP)、超声心动图各参数及药物不良反应(症状性低血压、高钾血症、肾功能下降、血管性水肿等)的变化。 [结果]经治疗后最大耐受剂量组与低剂量组左心房内径(LAD)对比治疗前差异均有统计学意义(P＜0.05),但两组间差异无统计学意义(P＞0.05);两组左心室舒张期末内径(LVEDD)与治疗前比较均显著下降(P＜0.05),但两组间差异无统计学意义(P＞0.05);两组左心室射血分数(LVEF)与治疗前比较均显著升高(P＜0.05),程度相似(P＞0.05);最大耐受剂量组血清NT-proBNP水平下降幅度高于低剂量组,差异有统计学意义(P＜0.05);最大耐受量组药物相关不良反应发生率更高(17.5%比2.1%,P＜0.05)。 [结论]与低剂量组相比,最大耐受剂量组在改善心肌梗死后心力衰竭患者心脏重构和左心室射血功能上并没有显示出显著优势,虽然可能通过进一步降低NT-proBNP水平减少心血管事件发生,但严格滴定最大耐受剂量与频繁发生药物不良反应密切相关。     

Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion

BACKGROUND: Both fosinopril and valsartan are effective in protecting endothelial function. We hypothesized that they may also reduce myocardial no-reflow. In addition, suppression of adenosine triphosphate-sensitive K (KATP) channel opening is an important mechanism for myocardial no-reflow. Therefore, this study sought to assess the effect of fosinopril and valsartan on myocardial no-reflow and explore the possible mechanism. METHODS: Coronary ligation area and the area of no-reflow were determined with both myocardial contrast echocardiography in vivo and pathological means in 56 mini-swine randomized into seven study groups: eight in control, eight in fosinopril-pretreated (1 mg/kg/day) for 3 days, eight in fosinopril and glibenclamide (KATP channel blocker)-pretreated, eight in valsartan-pretreated (2 mg/kg/day) for 3 days, eight in valsartan and glibenclamide-pretreated, eight in glibenclamide-treated and eight in sham-operated. An acute myocardial infarction and reperfusion model was created with a 3-h occlusion of the coronary artery followed by a 2-h reperfusion. The levels of KATP channel proteins (SUR2, Kir6.1, and Kir6.2) in the reflow and no-reflow myocardium were quantified by Western blotting. RESULTS: Compared with the control group, both fosinopril and valsartan significantly improved ventricular function, decreased area of no-reflow (myocardial contrast echocardiography: from 78.5+/-4.5 to 24.5+/-2.7 and 24.3+/-3.6%, pathological means: from 82.3+/-1.9 to 25.2+/-3.2 and 24.9+/-4.4% of ligation area, respectively; all P<0.01), reduced necrosis size from 98.5+/-1.3 to 88.9+/-3.6 and 89.1+/-3.1% of ligation area, respectively (both P<0.05). They also increased the levels of SUR2 and Kir6.2 (P<0.01), but had no effect on the level of Kir6.1 (P>0.05). A combination of fosinopril or valsartan with glibenclamide significantly increased area of no-reflow (P<0.05) and decreased the levels of SUR2 and Kir6.2 (P<0.01). CONCLUSIONS: Pretreatment with fosinopril or valsartan can reduce myocardial no-reflow. This beneficial effect is due to activation of the KATP channel.     

Mitral regurgitation in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: prognostic significance and relation to ventricular size and function.

AIMS: Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes. METHODS AND RESULTS: We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction (P trend < 0.001). Moderate-severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1-5.3)], CV mortality [adjusted HR 2.7 (1.2-6.1)], hospitalization for HF [adjusted HR 2.5 (1.1-5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4-4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8-4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF (P < 0.001). CONCLUSION: Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.     

Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction

IMS: Recurrent myocardial infarction (MI) is common after a first MI and is associated with increased morbidity and mortality. Predictors and prognosis of a recurrent MI with contemporary management are not well known. METHODS AND RESULTS: We assessed the predictors and prognostic impact of a first recurrent MI in 10,599 patients with left ventricular dysfunction, heart failure, or both following a first MI from the Valsartan in Acute Myocardial Infarction Trial (VALIANT) cohort. During a median follow-up of 27.4 months, 861 patients (9.6%) had a recurrent MI. The median time to recurrence was 136 days (quartiles 35-361 days), with a declining rate of recurrent MI within the first 3 months. The strongest predictors of recurrent MI were reduced estimated glomerular filtration rate, unstable angina, diabetes, and age. Mortality was markedly elevated (20.5%) within the first 7 days of a recurrent MI. Patients who survived 7 days after a recurrent MI continued to be at increased risk of death compared with patients without a recurrent MI and the risk of death remained elevated more than two-fold a year after the recurrent MI (adjusted hazards ratio 2.4, 95% confidence interval 1.7-3.2). One-year mortality for the entire VALIANT cohort was 10.3%, whereas 38.3% of the patients were dead 1 year after recurrent MI. Early reinfarctions (within 1 month) was associated with significantly higher 30-day mortality than later reinfarctions. CONCLUSION: Even in the context of contemporary treatment, a recurrent MI confers a significantly increased risk of death in patients following a high-risk first MI. Strategies aimed at reducing recurrent MI will thus likely prolong survival in post-MI survivors.     

Acute blood pressure response to trandolapril and captopril in patients with left ventricular dysfunction after acute myocardial infarction

Objective Our purpose was to compare the blood pressure response to short-term treatment with captopril or trandolapril in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). Methods A multicenter, randomized, double-blind, double-dummy, parallel group study was performed. Treatment was initiated 3 to 10 days after the onset of symptoms. On day 1, patients received a single dose of captopril 6.25 mg, trandolapril 0.5 mg, or placebo in the morning. Treatment was then titrated upward over the next 5 days. Blood pressure was monitored with an automated device for the first 12 hours after dosing on day 1. Conventional blood pressure measurements were performed throughout the study. Results Of 205 patients treated in the study, 193 patients were evaluated for first-dose effects. In the captopril group, the maximum decrease in blood pressure occurred after 2 hours, and the magnitude of this decrease was significantly greater than in the other 2 groups: 8.8 ± 12/6.3 ± 8 mm Hg (captopril) versus 5.4 ± 10/3.1 ± 8 mm Hg (trandolapril) versus 2.4 ± 9/1.4 ± 7 mm Hg (placebo) (P < .01). In the trandolapril group, the maximum decrease occurred after 7 hours and the magnitude of this effect was similar in all 3 groups: 5.9 ± 11/3.6 ± 8 mm Hg (trandolapril) versus 4.3 ± 10/3.5 ± 8 mm Hg (captopril) versus 3.1 ± 11/2.8 ± 8 mm Hg (placebo) (not significant). Although there was a higher incidence of hypotension on day 1 in the captopril group, the overall incidence of hypotension during the study period was similar in both active treatment groups. Conclusion Because of differences in initial blood pressure response profiles, short-term treatment with trandolapril tended to be better tolerated than captopril in post-AMI patients with LV dysfunction. (Am Heart J 2002;143:313-8.)     

Fever after acute myocardial infarction in patients treated with intravenous timolol or placebo

Body temperature was studied in 65 patients admitted to hospital within four hours of the onset of symptoms of acute myocardial infarction. Thirty three patients had been randomly assigned to intravenous timolol treatment and 32 to placebo treatment. Infarct evolution was assessed by continuous vectorcardiography and creatine kinase release. Maximum and mean temperatures during the first eight days were significantly lower in the timolol group, who were discharged from hospital one day earlier. Eight patients in the placebo group had temperatures of greater than 39 degrees compared with one in the timolol group. Both the mean temperature and the maximum temperature correlated significantly with indices of infarct size and ischaemic area as estimated by cumulative creatine kinase release, QRS vector difference, and ST vector magnitude. The results were consistent with the view that reduction of infarct size may partly explain the reduced pyrexial response after timolol treatment. Other mechanisms are probably also involved in larger infarcts. Because high fever has detrimental haemodynamic effects in acute myocardial infarction, reduction of this response may be beneficial. The results support the early use of beta adrenoceptor blockade in acute myocardial infarction.     

QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in G?teborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.     

QT time in patients treated with alprenolol or placebo after myocardial infarction.

Studies were made on the effects of long-term beta-blockade on the QT interval in patients discharged alive from hospital after myocardial infarction. The patients (n = 230) in this study constituted all those who participated in the alprenolol study on postmyocardial patients in Göteborg, Sweden. The study was double-blind (alprenolol 200 mg b.i.d. or placebo) and randomised. The patients were divided into 4 risk groups (1-4) with different predicted mortality. The electrocardiograms before and after 8 weeks of treatment were analysed with respect to heart rate and QT time. There was a decrease in heart rate of about 10% in the alprenolol treated patients. The QT time was not significantly influenced by alprenolol. The rate corrected QT time (QTc) decreased in the subgroup of the most severely diseased patients (subgroup 4) treated with alprenolol.     

卡托普利对急性心肌梗死后室壁瘤形成的影响

目的:观察口服卡托普利对急性心肌梗死(AMI)后室壁瘤(VA)形成的影响。方法:住院首发AMI患者151例,年龄≥60岁,按是否口服卡托普利随机分为观察组及对照组。于病后4周行心脏二维超声检查.其中7例经左室造影,观察VA形成情况。结果:观察组89例,有VA形成9例,占10％;对照组62例,有VA形成21例,占34％(P<0.05)。心功能(killip)Ⅱ～Ⅲ级者:观察组6.7％(6/89),对照组18％(11/62),(P<0.05)。结论:口服卡托普利能减轻、延缓心室重构程度,减少VA形成,降低病死率。     

缬沙坦对急性心肌梗死大鼠左室重构及心功能的影响

目的 研究缬沙坦对大鼠急性心肌梗死（AMI）后左室重构及心功能的影响。方法 将80只雌性SD大鼠AMI后6 h随机分为:梗死对照组（MI-C组,n=30）、缬沙坦治疗组（MI-V组,n=30）及假手术组（Sham组,n=20）。MI-C组及MI-V组结扎冠状动脉左室支建立AMI模型,Sham组只在相同部位穿线后不结扎。MI-V组:将缬沙坦20 mg/(kg·d)以生理盐水15 ml/kg溶解后灌胃,每日2次,共7 d;MI-V组和Sham组:均以等量生理盐水灌胃,每日2次,共7 d。分别于AMI后12 h、3 d 及7 d,测定血流动力学,进行超声和形态学检查。结果 与Sham组比较,MI-C组的左室收缩压（LVSP）、左室内压最大上升速率（+dp/dt）和左室内压最大下降速率（-dp/dt）显著降低（分别为P<0.05及P<0.01）;左室舒张末压（LVEDP）显著增加（P<0.01）;左室舒张末期容积(LVEDV)、短轴(D)、左室相对质量（LVWI）逐渐增加,至7 d时显著增加（P<0.05或P<0.01）;长轴(L)、球形指数、短轴缩短率（FS）逐渐降低,至7 d时显著降低（P<0.05或P<0.01）。与MI-C组比较,MI-V组的LVSP、+dp/dt、-dp/dt显著回升（P<0.05或P<0.01）,LVEDP显著下降（P<0.05或P<0.01）,LVWI逐渐下降,至7 d时降低显著（P<0.05）,梗死范围从3 d、7 d开始显著减小（P<0.05）。LVEDV、D、LVWI及梗死范围均下降,至7 d时显著降低（P<0.05或P<0.01）,L、球形指数、FS逐渐升高,至7 d时显著上升（P<0.05或P<0.01）。结论 缬沙坦能减轻心肌梗死后左室构型的改变,改善早期AMI后大鼠的心功能,抑制左室重构,改善左室的功能。     

Late variation in ventricular function after myocardial infarction

To assess the possible role of variables not related to early infarct artery reperfusion in predicting late changes in ventricular function after infarction, paired early (mean 6.6 +/- 3.5 days after admission) and late (12.7 +/- 7.0 months later) cross-sectional echocardiograms from 54 infarction survivors were retrospectively reviewed. Ejection fraction was calculated from digitized biapical echocardiographic views on a graphics tablet. Changes of 0.10 or more in LVEF were correlated with 23 clinical variables. By stepwise regression analysis, Q-wave infarction and low early LVEF independently predicted late improvement in function. Early high LVEF and interval infarction were the only independent predictors of late declines in function. Overall, when patients were indexed by early left ventricular systolic function, a pronounced late "regression to the mean" was noted with initially high values tending to fall and low values to rise (r = -0.44, p less than 0.001). This effect must be accounted for in any acute intervention trial in myocardial infarction. The occurrence of Q-wave infarction does not exclude late improvement in ventricular function.     

Changes in ventricular function associated with coronary reperfusion in acute myocardial infarction

Currently there is no accepted method for measurement of myocardial infarct size in humans. Analysis of both global and regional left ventricular function provides an indirect indication of extent of myocardial necrosis. Acute coronary occlusion results in cessation of function and in some cases dilatation of the involved myocardial segment. Often there is reciprocal hyperfunction of the non-ischemic segments resulting in little impairment of global ventricular function. Average global left ventricular function does not change from hospital admission through hospital discharge in patients with acute myocardial infarction, treated conventionally. With successful coronary reperfusion, however, both regional and global ventricular function have been reported to improve over several weeks after the initial ischemic insult. Improvement in ventricular function is most likely to occur in patients with collaterals or some preservation of antegrade flow to the involved myocardial segment who successfully undergo reperfusion. Return of function occurs in 82% of patients successfully treated within two hours after onset of chest pain. Approximately 50% of patients successfully treated two to 18 hours after onset of chest pain have demonstrated significant improvement in function. Patients admitted with normal ventricular function are less likely to demonstrate improved global ventricular function than those admitted with ejection fractions less than 45%. Acute PTCA with or without thrombolysis may result in a greater return in function than thrombolysis alone. Delayed revascularization more than 48 hours after successful reperfusion does not appear to affect ventricular function a late follow-up but may improve probability of survival. Patients discharged with ejection fractions greater than 45% clearly have an improved prognosis compared to those with depressed ejection fractions post-myocardial infarction.