Overview of patency as an end point of thrombolytic therapy.

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.     

Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials

In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment.     

Coronary permeability and left ventricular function following thrombolytic therapy

We study 40 patients, 55 +/- 7 years old with acute myocardial infarction treated early by thrombolytic therapy (20 STK and 20 rt-PA). All patients were angiographically studied in the following conditions: 1) baseline, before initiating therapy. 2) Three hours after treatment. 3) Twenty four hours later. 4) Before discharge. The infarct related artery was patent 24 hours after treatment in 31 patients (78%); five of them were patent before treatment, and we observed an early reperfusion in 20 patients (57%) and late reperfusion in 6 patients (17%). The number of patients with angiographic evidence of intraluminal thrombus decreased progressively through conditions while the grade TIMI of coronary perfusion increased in the absence of reocclusion. Final regional wall motion of infarct related myocardial zones and their degree of recovery were significantly higher in recanalized patients, as compared with non-reperfused patients. Similarly, left ventricular functional recovery was higher in patients with antegrade of collateral flow to the infarct area, as compared with totally occluded patients.     

Determinants of improved left ventricular function after thrombolytic therapy in acute myocardial infarction

Many studies have been performed to evaluate the efficacy of thrombolytic therapy in achieving reperfusion, salvaging myocardium and enhancing survival. This review discusses the concordance between the results of these clinical studies and the observations made in experimental animals of the effect of reperfusion on the recovery of left ventricular function. The evaluation of functional recovery is affected by the timing of the measurement and the sensitivity of the method for detecting regional abnormalities. In addition, the underlying coronary anatomy also determines outcome, so that infarct location, collateral circulation and the degree of coronary obstruction merit consideration. Two factors are of paramount importance in determining the amount of myocardium salvaged, the recovery of left ventricular function and the reduction in mortality. These factors are: the time delay until reperfusion is achieved and the adequacy of the coronary reflow. The close agreement between studies measuring the effect of reperfusion on left ventricular function and studies with mortality as the end point provides indirect evidence that enhancement of survival in patients treated with thrombolytic agents is mediated by recovery of ventricular function.     

Effects of thrombolytic therapy on evolution of left ventricular function in acute myocardial infarction

Use of thrombolytic therapy in the early hours of acute myocardial infarction (AMI) has gained widespread acceptance. One potential benefit of early reperfusion could be improved left ventricular (LV) function. Experimental animal studies have demonstrated that duration of coronary occlusion determines ultimate infarct size and have also raised the issue of reperfusion injury. The evolution of LV function after AMI in man where there is no attempt at early reperfusion is discussed. Studies of LV function following thrombolytic therapy in man have illustrated the following points. Time to successful reperfusion appears to be a critical determinant for potential for LV functional recovery. If reperfusion is achieved within 2.5 hours after onset of symptoms, consistent recovery of function within the infarct zone appears to be possible. With reperfusion from 2.5 to six hours after onset of symptoms, there is no predictable, substantial improvement in either global or regional LV function. Within the framework of this general conclusion, there are three potential exceptions: Successful reperfusion up to six hours after onset of symptoms may prevent infarct expansion. Patients with subtotal occlusion of the infarct vessel prior to therapy in this time period may have more potential for recovery of LV function than those with initial total occlusion. A tight residual stenosis following thrombolytic therapy may mask potential for functional recovery in the infarct zone. Earlier diagnosis and treatment of AMI is one obvious solution for the overall lack of beneficial results on evolution of LV function seen in most studies to date.(ABSTRACT TRUNCATED AT 250 WORDS)     

Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the Second Mount Sinai-New York University Reperfusion Trial

The change in left ventricular ejection fraction from preintervention to predischarge was prospectively assessed in 393 patients with acute myocardial infarction. Within 12 h of symptom onset (mean 6.3 +/- 2.7 h), patients were randomly assigned to a double-blind intracoronary infusion of streptokinase, nitroglycerin, both streptokinase and nitroglycerin or conventional therapy without acute cardiac catheterization. Treatment effects were also assessed in prospectively defined angiographic subsets. There was a significant interaction between streptokinase and nitroglycerin (p less than 0.01), resulting in an increase in ejection fraction of 3.9 percentage units in the combined treatment arm (p less than 0.001). Patients with collateral flow to a totally obstructed infarct-related artery showed a significant improvement over those without collateral flow in the streptokinase (5.4 +/- 2.5%) and streptokinase-nitroglycerin (10.6 +/- 2.7%) arms, but not in the nitroglycerin arm. Time to treatment did not influence the change in ejection fraction. In patients with initial subtotal occlusion, thrombolytic therapy was of no short-term benefit because ejection fraction increased by 6% in all three intervention arms. These findings indicate that relatively late thrombolytic therapy results in significant myocardial salvage in those patients with collateralized total coronary occlusion. This benefit is potentiated by concomitant nitroglycerin therapy.     

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.     

Improved left ventricular function in myocardial infarction following intravenous thrombolytic therapy with acylated plasminogen activator

Forty-six patients with acute myocardial infarction (MI) were treated within three hours of the onset of chest pain with an intravenous bolus (IV) of 30 units of anisolated plasminogen activator streptokinase complex (APSAC). Reperfusion was detected in 31 patients (67%) by clinical, electrocardiographic, and enzymatic criteria. The mean time elapsed between the onset of the chest pain to thrombolytic therapy was 114 +/- 53 minutes. Left ventricular ejection fraction (LVEF) was significantly better in patients with anterior and inferior myocardial infarction who had successful reperfusion, as compared with those who did not (48.8 +/- 13.0 vs 35.3 +/- 10.9, p less than 0.05 and 59.7 +/- 12.6 vs 47.9 +/- 15.3, p less than 0.05, respectively). The rate of reocclusion within three weeks was 22%. The overall one-year mortality was 4%. There were no serious adverse reactions following the thrombolytic treatment. Thus bolus IV injection of 30 units of APSAC is both safe and effective in preserving left ventricular function when given early in the course of acute myocardial infarction.     

The influence of thrombolytic therapy on selected parameters of left ventricular function in acute myocardial infarction

Our study aimed to evaluate the influence of thrombolytic therapy on some left ventricle (LV) function parameters in patients with acute myocardial infarction. The study was performed on 44 pts admitted to hospital due to acute myocardial infarction. The patients were divided into two groups: I group--30 pts (26 male, 4 female) at average age 57 +/- 10 who were treated with tissue plasminogen activator (t-PA) routinely and II group--14 pts (9 male, 5 female) at average age 62 +/- 10 in whom thrombolytic therapy was contraindicated for various reasons. Transthoracic echocardiography was performed just before treatment (0), 3.5 hours after the onset of drug administration (2 hours after the end of t-PA injection) (1) and on the 10th day of hospitalization (2). Control group consisted of 16 clinically healthy individuals (12 male, 4 female) at average age 54 +/- 9. The following parameters were evaluated: DT-E--wave of early diastolic transmitral flow deceleration time, IVRT--isovolumic relaxation time, E/A--early/atrial peak flow velocity ratio of transmitral flow, LATEF%--left atrial total emptying fraction, EF--left ventricle ejection fraction. In patients with acute myocardial infarction shortening of DT, prolongation of IVRT, lower E/A ratio and decrease of LATEF% compared to controls were observed. In group I EF was less than in clinically healthy individuals. E/A ratio was higher in pts from group I than from group II. In patients treated with t-PA 2 hours after treatment as well as on the 10th day significant prolongation of DT, shortening of IVRT and increase of LATEF% were observed. These changes were accompanied by the increase of EF. In patients with acute myocardial infarction not treated with t-PA significant increase in E/A ratio and EF on 10th day were observed. On the basis of the results were conclude: In patients with acute myocardial infarction LV diastolic function and with unproper relaxation as well as unproper compliance of LV myocardium is present. In patients with thrombolytic therapy LV filling pattern improves just two hours after t-PA administration (DT prolongation, IVRT shortening, LATEF% increase). Such tendency remains on the 10th day after treatment. In patients without thrombolytic therapy slight improvement occurs no sooner than on the 10th day of the MI.     

Cardiac resynchronization therapy: an updateimpaired left ventricular systolic function

Cardiac resynchronization therapy has been shown to reduce hospitalization and mortality, and to improve heart failure symptoms, in patients with systolic dysfunction and ventricular dyssynchrony. We review the current guidelines for cardiac resynchronization therapy, the underlying evidence, the latest developments in the field and directions of future research.     

Pulmonary vein isolation as an end point for left atrial circumferential ablation of atrial fibrillation.

OBJECTIVES: We sought to determine whether elimination of pulmonary vein (PV) arrhythmogenicity is necessary for the efficacy of left atrial circumferential ablation (LACA) for atrial fibrillation (AF). BACKGROUND: The PVs often provide triggers or drivers of AF. It has been shown that LACA is more effective than PV isolation in eliminating paroxysmal AF. However, it is not clear whether complete PV isolation is necessary for the efficacy of LACA. METHODS: In 60 consecutive patients with paroxysmal (n = 39) or chronic (n = 21) AF (mean age 53 +/- 12 years), LACA to encircle the left- and right-sided PVs, with additional lines in the posterior left atrium and along the mitral isthmus, was performed under the guidance of an electroanatomic navigation system. The PVs were mapped with a decapolar ring catheter before and after LACA. If PV isolation was incomplete, no attempts at complete isolation were made. RESULTS: After LACA, there was incomplete electrical isolation of one or more PVs in 48 (80%) of the 60 patients. The prevalence of PV tachycardias was 82% before and 8% after LACA (p < 0.001). At 11 +/- 1 months of follow-up, 10 (83%) of the 12 patients with complete and 39 (81%) of 48 patients with incomplete PV isolation were free from recurrent AF without antiarrhythmic drug therapy (p = 1.0). A successful outcome was not related to the number of completely isolated PVs per patient (p = 0.6). CONCLUSIONS: Left atrial circumferential ablation modifies the arrhythmogenic substrate within the PVs. Complete electrical isolation of the PVs is not a requirement for a successful outcome after LACA.     

急性心肌梗塞静脉溶栓治疗改善左心室功能的作用

为评价急性心肌梗塞（ＡＭＩ）静脉溶栓再灌注对左心室功能及重塑的影响，应用二维超声心动图（２ＤＥ）对６１例ＡＭＩ接受静脉溶栓治疗的患者，分别在急性期及６个月后随访时测量并计算左心室容积（ＥＳＶ和ＥＤＶ），射血分数（ＥＦ），左心室内膜弧长（ＡＳＬ和ＰＳＬ）以及室壁运动指数（ＧＷ－ＭＩ和ＲＷＭＩ）。结果显示，以上各项指标急性期时两组比较差异均无显著性，在６个月后的随访中，再通组ＥＦ值明显高于未通组，再通组左室容量减小、变形减轻。急性期两组的心功能无差异，随访时再通组心功能较未通组显著改善。提示溶栓再灌注能明显减轻左心室的扩张及抑制左心室重塑，改善患者的心功能和预后。     

Use of the electrocardiogram as an aid in screening for left ventricular aneurysm.

Attempting to cull from a population of patients with coronary artery disease or cardiomyopathy, a subgroup in whom left ventriculography might most reasonably be performed in search of a surgically resectable ventricular aneurysm, the electrocardiograms (ECGs) and ventriculograms of 96 patients were analyzed. This study was conceived to test the value of the ECG as an initial screening technique. Patients with normal ventricular contractile motion in the presence of coronary artery disease rarely showed ST segment elevation exceeding 2 mm in any lead, and even more rarely showed Q waves in corresponding leads. All patients with well defined left ventricular aneurysms had at least 1 mm ST segment elevation, and the majority (73%) had ST elevation of 2 mm or greater; in 80% of these, there were associated Q waves in the same lead. In patients with only local areas of hypocontractility, the frequency of ST segment elevation with concomitant Q waves was significantly less (approximately 50%) than that seen in patients with aneurysms. It is concluded that patients with suspected or proven coronary disease who fail to demonstrate ST segment elevation are unlikely to have ventricular aneurysms and, thus, would receive little diagnostic benefit from left ventriculography. The presence of ST segment elevation, with or without associated Q waves in the same leads, is a helpful screening sign, raising the possibility of a surgically remediable lesion such as a ventricular aneurysm, but similar electrocardiographic patterns are also seen in patients with non-operable localized or generalized disorders of contraction. Having discovered ST elevation, then, left ventriculography becomes a reasonable next step - when otherwise indicated - in delineating the type of contractile disorder as well as the amount of adequately functioning muscle.     

Brief overview of the end points of thrombolytic therapy.

In addition to mortality, several measurable end points of thrombolytic therapy have been studied. These include coronary arterial patency, left ventricular function, reocclusion, reinfarction, and bleeding complications. Current wisdom dictates that recanalization of occluded arteries in the early phases of acute myocardial infarction should be attempted to preserve viable cardiac muscle, with the ultimate goal of decreasing mortality. Unfortunately, the number of patients eligible for thrombolytic therapy far exceeds the number receiving it, despite the clear benefits that have been demonstrated.     

Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction. TAMI Study Group

Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction.     

链激酶溶栓治疗急性心肌梗死对左心室功能的改善作用

为评价链激酶溶栓治疗急性心肌梗死（ＡＭＩ）对左心室功能的影响，应用二维超声心动图对２６例接受链激酶溶栓治疗的ＡＭＩ患者和２７例未溶栓的ＡＭＩ患者，分别在急性期及６个月后随访时测量并计算左心室容积（ＥＤＶ和ＥＳＶ），射血分数（ＥＦ）以及室壁运动指数（ＧＷＭＩ和ＲＷＭＩ）。以上各项指标在急性期时比较各组无显著性差异；在随访期再通组ＥＦ值明显高于未通组和未溶栓组，再通组左室容量减小。急性期各组心功能无差异，随访时再通组心功能较未通组显著改善。提示:链激酶溶栓能明显减轻ＡＭＩ患者的左心室扩张，改善左心室功能和长期预后     

老年急性心肌梗塞溶栓治疗对左心室功能的改善作用

目的 :评价链激酶溶栓治疗老年急性心肌梗塞 (AMI)对左心室功能的影响。方法 :应用二维超声心动图对 2 9例 AMI接受链激酶溶栓治疗和 2 1例未溶栓的 AMI患者 ,分别在急性期及 6个月后随访时测量并计算左心室容积 (EDV和 ESV) ,射血分数 (EF)等参数。结果 :急性各组心功能无差异。随访期再通组 EF值明显增加 ,且明显高于未通组和未溶栓组。结论 :链激酶溶栓能明显减轻老 AMI患者的左心室扩张 ,改善左心室功能和长期预后