Determinants of infarct size after thrombolytic treatment in acute myocardial infarction.

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.

Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction. Results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188-treated patients demonstrated a 38% reduction in median myocardial infarct size (25th and 75th percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P = .031), greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P = .033), and a 13% relative improvement in median ejection fraction (52% [43, 60] versus 46% [35, 60]; P = .020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1% versus 13%; P = .016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. CONCLUSIONS: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

Myocardial infarct artery patency and reocclusion rates after treatment with duteplase at the dose used in the International Study of Infarct Survival-3. Burroughs Wellcome Study Group.

Duteplase, 98% double-chain recombinant tissue-type plasminogen activator, was administered intravenously in 488 patients with acute myocardial infarction in a multicenter, open, safety and patency study. Duteplase dosing was based on body weight. Duteplase was administered as a bolus of 0.04 MIU/kg of thrombolytic activity followed by 0.36 MIU/kg over 1 hour and 0.067 MIU/kg/hour for 3 additional hours. The patency rate of the infarct-related artery at 90 minutes was 69% (330 of 478). The reocclusion rate at 3 to 48 hours was 6% (18 of 301). Reinfarction occurred in 7.6% of patients (37 of 488), but 12 reinfarctions occurred after coronary angioplasty. Serious bleeding occurred in 7.6% of patients (37 of 488), predominantly at the catheterization entry site. There were 3 instances of central nervous system bleeding, 1 fatal. Fibrinogen levels declined to 83% of baseline at 24 hours. Weight-based dosing may explain the low incidence of serious bleeding in this study. The in-hospital mortality was 6.6% (32 of 488). This study documents that the dose of duteplase used in the International Study of Infarct Survival-3 results in a 90-minute coronary artery patency rate and safety profile comparable to those reported in published studies on the approved dose of alteplase.

Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease.

Adenosine is an endogenously produced compound that has significant effects as a coronary and systemic vasodilator. Previous studies suggest that intravenous infusion of adenosine, coupled with thallium-201 scintigraphy, may have specific value as a noninvasive means of evaluating coronary artery disease. The purpose of this study was to compare the diagnostic value of adenosine thallium testing with that of standard exercise thallium testing. One hundred subjects were studied with exercise thallium imaging and thallium imaging after adenosine infusion, including 47 with angiographically proved coronary artery disease and 53 control subjects. The overall sensitivity of the thallium procedures was 81% for the exercise study and 83% for the adenosine study (p = NS); the specificity was 74% for the exercise study and 75% for the adenosine study (p = NS). The diagnostic accuracy of the exercise study was 77% and that of the adenosine study was 79%. Ninety-four percent of subjects had an adverse effect due to the adenosine infusion; however, most of these effects were mild and well tolerated. All adverse effects abated within 30 to 45 s of the termination of the study, consistent with the very brief half-life of the agent. Thus, thallium-201 scintigraphy after intravenous infusion of adenosine has a diagnostic value similar to that of exercise thallium testing for evaluation of coronary artery disease. Adenosine thallium testing may be particularly useful in evaluating patients unable to perform treadmill exercise testing.

Use of femoral artery guiding catheters via the left brachial artery for transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty using the right brachial artery has been described using either a cutdown and arteriotomy or a percutaneous entry. Each method requires the use of a brachial artery guiding catheter (Stertzer guiding catheter; (USCI). This communication reports the use of percutaneous entry of the left brachial artery and coronary angioplasty performed with femoral guiding catheters. In this manner coronary angioplasty has been successfully performed in 42 of 47 patients (90%) without major complications.

Effect of ischemia on ventricular contractility in patients with coronary artery disease.

The constant of elastance (E-MAX) is determined by measuring continuous left ventricular pressure and volume changes during the cardiac cycle. To evaluate the effect of myocardial ischemia on contractility, E-MAX was measured from serial pressure volume loops at baseline, with atrial pacing-induced ischemia, and after the administration of intravenous nitroglycerin with repeat pacing. Ten patients undergoing cardiac catheterization for presumed coronary artery disease were evaluated by this method. The severity of the coronary artery disease was graded angiographically by using the Gensini coronary score. In 8 of the 10 patients there was a significant decrease in E-MAX during atrial pacing (P less than .05). With the administration of nitroglycerin there was an attenuation of the ischemic effect previously noted with pacing. In 3 of the 10 patients administration of nitroglycerin produced a further decrease in E-MAX with ischemia. All 3 patients had a significantly lower Gensini coronary score with a well-developed, visible coronary collateral network. The authors' results indicate that continuous pressure volume loop analysis is possible using the nuclear stethoscope. Significant ischemic changes are seen with atrial pacing, which are relieved by the administration of nitroglycerin, except in the presence of coronary collaterals.

Hugging balloon coronary angioplasty of a large left circumflex coronary artery.

A case is described in which hugging balloons were used to perform coronary angioplasty through a single catheter. A discussion concerning selection of balloon combinations and technique is included.

Stress thallium-201 imaging after coronary angioplasty predicts restenosis and recurrent symptoms.

The predictive accuracy of thallium imaging for the diagnosis of restenosis after angioplasty was evaluated in 121 patients who had undergone a successful procedure. Patients were evaluated three times over a 1 year follow-up period for symptoms, electrocardiographic (ECG) changes during exercise and the presence of reversible ischemia on exercise thallium imaging. At initial evaluation (4 to 6 weeks after angioplasty), 104 patients (86%) were asymptomatic. Of the 17 patients with chest pain symptoms, 9 had reversible ischemia on thallium imaging and all had restenosis. Of the 104 asymptomatic patients, 26 (25%) had a positive thallium scan (reversible ischemia) and this sign identified a high risk group. Evidence of restenosis was present by 6 months in 22 (85%) and by 1 year in 25 (96%) of these 26 patients. The largest group of patients manifested symptoms by the second evaluation (between 3 and 6 months after angioplasty). Of 28 patients with symptoms and a positive thallium scan at this evaluation, 26 had restenosis; on initial evaluation, 22 of these 26 patients had no symptoms but had had a positive thallium study. Ten of the 65 patients in the asymptomatic group had a positive thallium scan, but the scans of this group were not as predictive for recurrent symptoms as were those of the same group at initial evaluation. The 74 patients who had a negative thallium scan at 3 to 6 months with or without associated symptoms had a low likelihood of developing restenosis or symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of ambulatory radionuclide monitoring of left ventricular function early after acute myocardial infarction for predicting residual myocardial ischemia.

Ambulatory radionuclide monitoring of left ventricular function was performed with the nuclear Vest device in 35 patients early after acute myocardial infarction. Patients were evaluated during post-infarction treadmill, other activities that included mental stress and cold pressor challenge, and with stress thallium imaging and cardiac catheterization. Of the 35 patients evaluated, 14 had ischemic responses on treadmill testing and 21 had negative responses. By contrast, 20 had redistribution by thallium imaging suggesting ischemia. Vest studies demonstrated 56 responses suggestive of ischemia in 23 patients. Twenty-two occurred during exercise and 13 with mental stress. Seventy-five percent were silent and only 39% had associated electrocardiographic changes. Vest responses were compared in patients whose thallium scan was indicative of ischemia (thallium-positive) and those without ischemia (thallium-negative). Ejection fraction was higher in the thallium-positive group (0.52 +/- 0.11), as compared with thallium-negative patients (0.44 +/- 0.1). With exercise, ejection fraction decreased for the thallium-positive patients from 0.52 +/- 0.11 to 0.40 +/- 0.09 at peak exercise. For thallium-negative patients, ejection fraction changes were not significant. During mental stress, ejection fraction decreased from 0.51 +/- 0.11 to 0.45 +/- 0.12 for thallium-positive patients while thallium-negative patients were unchanged. Vest-measured decreases in ejection fraction of greater than or equal to 5 units during exercise were highly sensitive (90%), specific (73%) and predictive (82%) of a positive thallium scan. The same response for mental stress was specific (87%) and predictive (85%) of a positive scan result.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparable effects of intravenous nitroglycerin and intravenous nitroprusside in acute ischemia.

Forty patients with unstable angina were randomized to therapy with intravenous nitroglycerin (NTG) or nitroprusside (NTP). Invasive hemodynamic measurements were compared in both treatment groups and were used in concert with serial radionuclide monitoring of left ventricular function as patients were titrated to a therapeutic dose. Of the 22 patients randomized to intravenous NTG, there were 18 responders. Cardiac output significantly increased 28%, from 5.0 to 6.5 L/min at maximum effect. Mean pulmonary capillary wedge pressure (PCWP) decreased from 19 to 12 mm Hg. Mean arterial pressure decreased 10% and heart rate was unchanged (82 beats/min pre-treatment, 81 beats/min post-treatment). Radionuclide determined ejection fraction (EF) increased an average of 0.13, from 0.45 to 0.58. Peak filling rate paralleled increases in EF, increasing from 2.2 to 3.4 EDV/sec at peak level. Hemodynamic and radionuclide responses in the intravenous NTP group were compared to those with NTG. Of 18 patients randomized to NTP, 15 responders increased cardiac output from 5.1 to 6.8 L/min, a 35% increase. PCWP was 18 mm Hg at baseline and 10 mm Hg at peak effect. Mean arterial pressure decreased 13%, which was not significantly different from the NTG group. Heart rate response was identical to that in the NTG group. Ejection fraction increased an average of 0.17, from 0.43 to 0.60. Similar improvements were seen in peak filling rate (2.09 to 3.3 EDV/sec). There were no baseline differences between the NTG and NTP groups. In these patients NTG and NTP demonstrated equal efficacy, with the majority of patients showing substantial improvement in acute hemodynamics and left ventricular function with either agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of intravenous metoprolol in acute myocardial infarction: the role of anatomic subsets in predicting patient response.

The acute effects of intravenous metoprolol were evaluated in 30 patients with myocardial infarction by means of serial hemodynamic and radionuclide measurements of left ventricular function. Within 1 hour of completion of the metoprolol dosing, 90% of the patients underwent cardiac catheterization to define anatomy and to assess patients for interventional therapy; the remainder had catheterization by 72 hours. All patients tolerated intravenous metoprolol without significant side effects. Patient responses to therapy were divided into two groups based on the angiographic findings. At catheterization, all group 1 patients had visible collaterals to or a patent vessel supplying the vascular distribution of the infarction. All group 2 patients had occluded coronary arteries without evidence of collaterals to the infarct zone. Group 1 (n = 13) improved both systolic and diastolic left ventricular function (mean ejection fraction [EF] = 46% to 55%, peak filling rate [PFR] = 2.1 to 3.2 Edv/sec), while group 2 (n = 17) patients were unchanged (EF = 43% to 42%, PFR = 2.0 to 1.9). Patient characteristics and time to treatment were similar in both groups, as were the hemodynamic effects of metoprolol. Heart rate decreased 20% in group 1 and 22% in group 2 and cardiac output fell 22% in group 1 and 32% in group 2. Acute improvement in ventricular function in these patients appears to be closely related to the coronary anatomy, and in those with flow to the infarct zone, intravenous metoprolol may be effective in preserving left ventricular function.

Incomplete revascularization in multivessel percutaneous transluminal coronary angioplasty: the role for stress thallium-201 imaging.

Evaluation of patients with multivessel coronary disease for percutaneous transluminal coronary angioplasty raises the question: Is incomplete revascularization an acceptable procedure in these patients, or does complete revascularization need to be performed, as in coronary artery bypass grafting? To provide an answer the present study utilized exercise thallium imaging as a guide to the performance of angioplasty in 85 patients with multivessel coronary disease. Preangioplasty exercise thallium imaging helped to identify the primary stenosis ("culprit lesion") in 93% of patients. Two weeks to 1 month after dilation of this lesion, repeat thallium imaging identified two patient groups: Group 1, 47 patients with no evidence of ischemia in a second vascular distribution and Group 2, 38 patients with evidence of further angioplasty. In Group 2 47% of patients had angioplasty of a second vessel and 79% required multivessel angioplasty at 1 year follow-up. In contrast, only six Group 1 patients (13%) required angioplasty of a second vessel at 1 year. Thus, incomplete revascularization may be an acceptable approach in many patients with multivessel coronary disease. Stress thallium-201 imaging may be a useful technique in the evaluation and management of these patients.

Verapamil prophylaxis of migraine. A double-blind, placebo-controlled study.

We undertook a double-blind, placebo-controlled study to determine the effectiveness of verapamil hydrochloride for the prophylaxis of migraine. Twelve patients were given either verapamil hydrochloride, 80 mg four times daily, or placebo in random order during two consecutive three-month periods. Migraine frequency, severity, and duration were quantified by daily logs and monthly questionnaires. Ten of the 12 patients had fewer migraines during verapamil therapy. Migraine frequency decreased from 6.7 to 3.8 migraines per patient per month, for a mean decrease of 49%. Headache unit index fell from an average of 0.61 to 0.44. We conclude that verapamil is effective in the prophylaxis of migraine and that verapamil might be considered one alternative in the development of a regimen for the prophylaxis of migraine.