Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flecainide versus quinidine: results of a multicenter trial

In this multicenter trial, the efficacy and safety of flecainide, a new antiarrhythmic agent, were compared with those of quinidine, a standard antiarrhythmic agent in the United States. A randomized, parallel, placebo-controlled design was used. Flecainide was more effective than quinidine (p less than 0.0001) in reducing ventricular premature complexes, couplets and ventricular tachycardia. Flecainide continued to be effective in reducing ventricular arrhythmias during a 12-month follow-up period. The incidence of side effects was similar for the 2 drugs in both short- and long-term studies. Therefore, flecainide should be an excellent drug to use in treating patients with ventricular arrhythmias classified as either benign or potentially malignant.     

French multicenter trial of anistreplase versus heparin in acute myocardial infarction

Summary Eighty-four patients aged less than 71 years with less than 4-hour duration acute myocardial infarction (AMI) were randomized in a multicenter study to 30 U anistreplase or heparin (single injection of 6500 IU followed by 1000 IU/hr). Early reperfusion was assessed from ECG changes (50% of sum ST decrease 2 hours postdosing) and the CK release profile (CK peak <16 hours after onset of symptoms, CK slope >10%hr). Reperfusion rates in patients meeting at least two criteria of reperfusion were 62.5% on anistreplase versus 27.5% on heparin. On delayed angiogram (13.7±3.4 days), patency rates were 66% with anistreplase versus 47% (NS) with heparin in 76 patients. Global LVF was similar in both groups. With anistreplase, the mean lowest fibrinogen level was 0.43±0.55 g/l, plasminogen was 20±9%, and the highest F.D.P. was 1447±548 g/ml. All values recovered by hour 48. In-hospital and 1-year follow-up mortality was 7.2% (three patients) with anistreplase versus 10.2% (four patients) with heparin. Bleeding occurred in 9.7% and 5.1% of the patients (NS), respectively. No intracranial hemorrhage occurred. Thus, with combined clinical criteria or reperfusion, anistreplase is twice as efficient as heparin, has a good tolerance, and is easy to use as a single injection. Anistreplase is the generic name ofEminase, a registered trademark of Beecham Pharmaceuticals.This paper was presented, in part, at the 3rd Cardiovascular Pharmacotherapy International Symposium, October 15–19, 1989, Kyoto, Japan.     

Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized,double-blind multicenter trial

OBJECTIVES: This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation (AF). BACKGROUND: Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation, but data regarding biphasic shocks for conversion of AF are still emerging. METHODS: In an international, multicenter, randomized, double-blind clinical trial, we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF. Patients received up to five shocks, as necessary for conversion: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform. RESULTS: Analysis included 107 monophasic and 96 biphasic patients. The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels (100 J: 60% vs. 22%, p < 0.0001; 150 J: 77% vs. 44%, p < 0.0001; 200 J: 90% vs. 53%, p < 0.0001). Through four shocks, at a maximum of 200 J, biphasic performance was similar to monophasic performance at 360 J (91% vs. 85%, p = 0.29). Biphasic patients required fewer shocks (1.7 +/- 1.0 vs. 2.8 +/- 1.2, p < 0.0001) and lower total energy delivered (217 +/- 176 J vs. 548 +/- 331 J, p < 0.0001). The biphasic shock waveform was also associated with a lower frequency of dermal injury (17% vs. 41%, p < 0.0001). CONCLUSIONS: For the cardioversion of AF, a biphasic shock waveform has greater efficacy, requires fewer shocks and lower delivered energy, and results in less dermal injury than a monophasic shock waveform.     

Cardiovascular events in Japan. Lessons from the J-ACCESS multicenter prognostic study using myocardial perfusion imaging

The multicenter Japanese-Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), which involved 117 institutions and 4,629 patients, was the first attempt to quantify cardiac events and survival using stress-rest-gated single-photon emission computed tomography myocardial perfusion images (MPI) and QGS software in Japan. A 3-year follow-up study showed a relatively lower incidence of hard events than in the USA and some European countries, but a similar role of perfusion and left ventricular (LV) function. A low event risk with normal MPI and a higher incidence of major cardiac events in patients with large perfusion defects and LV dysfunction were defined. MPI was useful even among patients with proven coronary artery stenosis. The association between diabetes and chronic kidney disease (CKD) was an important predictor of cardiac events and the risk was evaluated using new software and risk charts. Additional studies were extended to include asymptomatic diabetes (J-ACCESS 2) and CKD (J-ACCESS 3). Because risk estimation is linked to the national healthcare system and clinical practice, optimal risk stratification and guidance for therapeutic strategies are recommended.     

Two-year results of a randomized,phase III comparative trial of telbivudine versus lamivudine in Chinese patients

Purpose

The burden of chronic hepatitis B infection is high in China, where prevalence exceeds 7 %. This was a randomized, double-blinded, phase III study of the efficacy and safety of telbivudine and lamivudine treatment at 104 weeks in Chinese patients with chronic hepatitis B.

Methods

Hepatitis B e antigen-positive (n = 290) and -negative (n = 42) adults with nucleoside analog–naïve compensated chronic hepatitis B were randomized to receive telbivudine 600 mg/day or lamivudine 100 mg/day for 104 weeks. The primary endpoint was reduction from baseline in serum hepatitis B virus (HBV) DNA at week 52. Week 104 analyses included HBV DNA reductions, undetectable HBV DNA (<300 copies/mL), ALT normalization, and e-antigen loss/seroconversion. Efficacy at week 104 was also assessed as a function of week 24 HBV DNA.

Results

In the intention-to-treat population (n = 332) at week 104, telbivudine was superior to lamivudine for reduction of HBV DNA [?5.48 vs. ?4.00 log₁₀ copies/mL; difference ?1.49 log₁₀ (95 % confidence interval ?2.2, ?0.8); p < 0.0001], for the proportion with undetectable HBV DNA (61.9 vs. 38.5 %; p < 0.0001), for ALT normalization (75.8 vs. 61.3 %; p = 0.0049), and for e-antigen loss (39.9 vs. 28.2 %; p = 0.0373). The cumulative probability of genotypic drug resistance was 15.4 % on telbivudine versus 23.6 % on lamivudine through week 104. Early virologic response at week 24 was associated with improved outcomes at week 104. Adverse events were similar to those seen in the GLOBE study.

Conclusions

Telbivudine is superior to lamivudine over 2 years of chronic hepatitis B treatment in Chinese patients.     

Cartography of absolute myocardial perfusion with magnetic resonance imaging. Methods and results

Ultra-rapid dynamic MRI (one image per heart beat) can follow the progression of the intra-myocardial signal during the first passage of diffusable gadolinium chelates injected as a bolus through a peripheral vein. A quantitative evaluation of myocardial perfusion is possible using a compartmental model of analysis. Absolute myocardial flow can be measured at rest and during hyperaemia induced by dipyridamole. It is possible to associate functional mapping, corresponding to parametric images of the flow indices, to the global evaluation. The ratio between the values obtained during hyperaemia and under basal conditions correspond to the myocardial reserve. The principles, results and limitations of this method are discussed in the light of published results, underlining the advantages of absolute flow measurement and of the differences between the results of MRI and myocardial scintigraphy.     

腺苷负荷心肌灌注显像在老年冠心病患者诊断中的价值

目的评价腺苷负荷心肌灌注显像试验对老年人冠心病的诊断价值以及对病变血管部位、血管支数、狭窄程度所作的评估。方法选择116例可疑冠心病的老年患者,行腺苷负荷心肌灌注显像。腺苷注射液按140μg/(kg.min)在6min内匀速静脉泵入。当腺苷泵入3min时经三通管快速静推99m锝-2-甲氧基异丁基异腈(99mTc-MIBI);1.5h后进行心肌灌注断层显像。若显像异常,次日行静息心肌显像。所有患者腺苷负荷心肌灌注显像后行冠状动脉造影。结果在116例患者中,73例冠状动脉造影显示明显的冠状动脉狭窄病变,其中单支病变22例,两支病变32例,三支病变19例。腺苷负荷心肌灌注显像试验诊断冠心病的敏感度、特异度和准确度分别为87.7%、72.1%和65.5%。诊断单支、两支和三支冠状动脉病变患者的敏感度分别为59.1%、84.4%和89.5%(P0.05)。对管径狭窄为50%～75%组的敏感度为57.1%,管径狭窄≥75%组的敏感度为89.4%,两组间比较有统计学意义(P0.05)。无论是单支病变、两支病变还是三支病变,累及前降支血管病变的心肌核素的阳性率均高(P0.05)。行血管内超声检查的17例患者中,有7例病变斑块面积狭窄率50%或管腔面积4mm2,有偏心或不稳定性斑块,给予冠脉介入治疗,而此7例腺苷负荷心肌核素均为阳性。结论腺苷负荷心肌灌注断层显像诊断老年患者冠心病的敏感度与冠脉狭窄程度和病变支数相关。对重度狭窄和两支、三支病变的患者有较高的敏感度,但对轻中度狭窄和单支病变的患者敏感度较低。腺苷负荷心肌灌注断层显像预测左前降支病变的阳性符合率高于左回旋支和右冠状动脉,且对临界病变的预测有一定价值。     

Real-time perfusion imaging: a new echocardiographic technique for simultaneous evaluation of myocardial perfusion and contraction

Myocardial contrast echocardiography (MCE) with high acoustic energy and triggered harmonic imaging is the best established ultrasound technique to date for the assessment of myocardial perfusion. With this technique, however, the ultimate goal of MCE (noninvasive real-time simultaneous assessment of myocardial perfusion and function after an intravenous injection of microbubbles) is not met. Recently, technologic advances have enabled myocardial opacification to be visualized during low-energy real-time imaging. During real-time perfusion imaging, wall motion and myocardial perfusion may be assessed simultaneously, obviating the need of the presently time-consuming combination of different imaging modalities. When high-energy ultrasound bursts are periodically transmitted to produce bubble destruction during low-power imaging, the consecutive frames after destruction delineate the restoration of contrast intensity. Microbubble replenishment rate and peak intensity may be determined subsequently, and provide reliable quantitative parameters of regional microcirculatory flow. This review will introduce the modalities used for real-time perfusion imaging with focus on power pulse inversion imaging and quantitative analysis. Furthermore, we will describe the clinical role the technique may have in the identification of coronary artery disease, quantification of coronary stenosis severity, assessment of myocardial viability, determination of infarction size, and evaluation of reflow and no- or low-reflow after acute myocardial infarction.     

Technetium Tc 99m sestamibi myocardial perfusion imaging: current role for evaluation of prognosis.

Like 201Tl imaging, technetium Tc 99m sestamibi (MIBI) myocardial imaging can be used with exercise and pharmacologic testing to assess the presence of coronary artery disease. An increasing body of literature indicates that MIBI can also be used to assess risk of future cardiac events such as myocardial infarction or death. This article summarizes the current status of MIBI imaging for evaluating prognosis in patients with known or suspected coronary artery disease.     

High dose intravenous streptokinase for acute myocardial infarction: preliminary results of a multicenter trial

To assess the efficacy of intravenous streptokinase in patients with acute myocardial infarction, 40 patients (30 men and 10 women, mean age 54 years) with acute myocardial infarction were given 1.5 million U of streptokinase intravenously in 1 hour, and coronary arteriography was performed repeatedly to assess reperfusion. Streptokinase treatment was begun 270 +/- 86 (mean +/- SD) minutes after the onset of chest pain. Of the 40 patients, 34 had total or near total coronary occlusion before streptokinase administration. In 14 (41%) of these 34 patients, some reperfusion occurred during the 90 minutes after the administration of streptokinase, but in only 11 of the 14 was reperfusion present at 90 minutes. After streptokinase administration, all patients received heparin for 8 to 10 days; they were subsequently administered aspirin and dipyridamole. Clinical evidence of reocclusion during the first 24 hours of heparin therapy occurred in one patient. Thus, when given to patients with acute myocardial infarction and total coronary occlusion an average of 4 1/2 hours after the onset of chest pain, high dose intravenous streptokinase achieves reperfusion in only about 40% and results in sustained reperfusion in only about 30%.     

Effectiveness of geriatric evaluation and care. One-year results of a multicenter randomized clinical trial

The aim of this study was to demonstrate the effectiveness of outpatient elderly care based on Comprehensive Geriatric Assessment (CGA). Eleven hospital Geriatric Evaluation and Management units (GEMs) systematically screened 1386 inpatients over a 10-month period, using the same uniform selection plan which included 15 programmed exclusion-inclusion criteria and a standard CGA. At the end of this screening, 152 eligible frail elderly patients were randomized to either a comprehensive outpatient GEMs program (intervention group: N=79) or to usual care by their family doctors (control group: N=73). We did not find any statistically significant difference between the two groups at entry. During the one-year follow-up period, 6 GEMs patients (7.6%) and 12 controls (17.1%) died, without significant differences between the two survival curves. Only three patients (all controls) ultimately dropped out, and eight (3 unit patients and 5 controls) entered a nursing home. GEMs patients were significantly more likely to have individual improvement in mental status (p=0.006), morale (p=0.024) and functional level (p=0.023), compared to controls. Even though intervention participants spent fewer days in hospital and nursing home (p<0.05), they received much more home care and day-hospital assistance (p<0.001), which explains why total expenditure on health care was the same in the two groups. We conclude that: 1) a standardized selection plan may contribute to identify the older inpatients in need of CGA; and 2) CGA-based outpatient care may be clinical- and cost-effective if directly managed by GEMs, and may provide targeted older patients with more substantial benefits than standard care, without inflating health care expenses.     

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.     

Noninvasive evaluation of ischaemic heart disease: myocardial perfusion imaging or stress echocardiography?

5. Clinical implications and conclusions     

Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo-controlled double-blind international multicenter trial. Ritanserin in Alcoholism Work Group

Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising effects on alcohol intake behavior in both animal and preliminary human studies. To test its effectiveness in alcohol dependence this phase III clinical trial was initiated. In a placebo-controlled, randomized, double-blind international multicenter study 493 patients with moderate or severe alcohol dependence (DSM-III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months. Ritanserin was well tolerated. The most frequent adverse experiences were headache and insomnia. A small increase in weight in the ritanserin-treated patients was observed. There were no significant differences between any dose of ritanserin and placebo in the relapse-rate, the time to relapse, craving for alcohol, or quantity and frequency of drinking after relapse. So far, neither ritanserin nor any other serotonergic medication has shown its specific effectiveness in relapse prevention in alcohol dependence.     

Single nocturnal dose of ranitidine in the treatment of duodenal ulcer: results of an open multicenter, comparative trial

This prospective multicentric randomized open trial was designed to evaluate the efficacy of ranitidine 150 mg bid vs 300 mg nocte in the short-term (4 weeks) treatment of duodenal ulcer in 15 Brazilian centers. On the basis of a randomization table 190 patients with endoscopically confirmed duodenal ulcer were allocated to receive either ranitidine 150 mg bid (94 pts) or 300 mg nocte (96 pts). The 2 treatment groups were well matched for age, sex, duration of ulcer disease, number and size of ulcers, duration of current episode, intensity of ulcer pain, alcohol and coffee intake and smoking habits. They were endoscopically controlled at the end of the 4 weeks. At 4 weeks 78 of 94 patients (83.0%) had their ulcers healed with the 150 mg bid regimen as opposed to 79 of 96 patients (82.3%) allocated to the 300 mg nocte dosage. This difference was not statistically significant. Ulcer symptoms diminished with treatment in both groups. The tolerability and compliance was excellent in both groups. The results show that ranitidine 300 mg nocte is as effective in the short-term treatment of duodenal ulcer as ranitidine 150 mg bid. Considering the greater simplicity of administration enhancing patient compliance, the treatment with 300 mg nocte is preferable.