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Biomedical subjects

R S Stack

Publications and source records attributed to R S Stack.

At least 37 records · Page 2Linked to original sources

Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group.

Recent trials of myocardial reperfusion using single-agent thrombolytic therapy and sequential cardiac catheterization have supported a conservative approach to the patient with acute myocardial infarction. To evaluate combination thrombolytic therapy and the role of a previously untested strategy for the aggressive use of cardiac catheterization, we performed a multicenter clinical trial with a 3 x 2 factorial design in which 575 patients were randomly allocated to one of three drug regimens--tissue-type plasminogen activator (t-PA) (n = 191), urokinase (n = 190), or both (n = 194) - and one of two catheterization strategies--immediate catheterization with angioplasty for failed thrombolysis (n = 287) or deferred predischarge catheterization on days 5-10 (n = 288). Patients with contraindications to thrombolytic therapy, cardiogenic shock, or age of more than 75 years were excluded. Global left ventricular ejection fraction was well preserved and almost identical at predischarge catheterization (54%), regardless of the catheterization or thrombolytic strategy used (p = 0.98). Combination thrombolytic therapy was associated with a less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04) and a lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%). When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04) and with a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens. No difference in bleeding complication rates was observed with any thrombolytic regimen. The aggressive catheterization strategy led to an overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065). The aggressive strategy improved regional wall motion in the infarct region (-2.16 SDs/chord) compared with deferred catheterization (-2.49 SDs/chord) (p = 0.004). More patients treated with the aggressive strategy were free from adverse outcomes (67% versus 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016). No significant increase in use of blood products resulted from the aggressive strategy.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary

Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog.

Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.

Animals

Rapid and accurate diagnosis of pulmonary emboli in a canine model using intravascular ultrasound imaging.

We utilized intravascular ultrasound (IVUS) imaging in a canine pulmonary embolism model to visualize experimental emboli. The images obtained were compared with those obtained by single-plane pulmonary arteriography in each of six animals. The vessel lumen appeared patent by both methods prior to injection of autologous clot. After thrombi were injected, the vessels were again imaged using both techniques. Intravascular ultrasound was 100 percent sensitive in detecting emboli, and visualization was always rapid. There were no complications. It appears that IVUS imaging is a sensitive method for documenting the presence of clot in a canine pulmonary embolism model.

Animals

Results of high dose intravenous urokinase for acute myocardial infarction.

To determine the outcome of patients after treatment with high-dose intravenous urokinase (3 million U) 102 patients were prospectively evaluated in the setting of acute myocardial infarction. The first 61 patients received intravenous urokinase as a continuous infusion and the last 41 patients were treated with an initial 1.5 million U intravenous bolus. Sixty-two percent of all patients had patent infarct-related arteries by the time of immediate angiography (median time 2.2 hours), which was performed in all patients. There was no significant difference in patency rates between patients treated with or without an initial intravenous bolus. Twenty-eight (28%) patients developed clinical evidence of recurrent ischemia (death, reocclusion, emergency angioplasty, urgent bypass surgery) during hospitalization, whereas only 7 (7%) developed angiographically documented reocclusion. Of 28 patients who failed to achieve successful reperfusion at the time of immediate catheterization, rescue angioplasty was technically successful in establishing reperfusion in all but 1 patient. No significant improvement in median global left ventricular function was seen between immediate (48%) and follow-up catheterization (48%). Significant bleeding complications were unusual except in 1 patient who experienced an intracranial hemorrhage. Eight (8%) patients died during hospitalization. Therefore, the use of high-dose intravenous urokinase in patients with acute myocardial infarction is associated with a 62% patency rate, a low incidence of reocclusion and bleeding complications and a high technical success rate with rescue angioplasty at the time of immediate catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Detection of restenosis after elective percutaneous transluminal coronary angioplasty using the exercise treadmill test.

To determine the value of a 6-month exercise treadmill test for detecting restenosis after elective percutaneous transluminal coronary angioplasty (PTCA), 303 consecutive patients with successful PTCA and without a recent myocardial infarction were studied. Among the 228 patients without interval cardiac events, early repeat revascularization or contraindications to treadmill testing, 209 (92%) underwent follow-up angiography, and 200 also had a follow-up treadmill test and formed the study population. Restenosis (greater than or equal to 75% luminal diameter stenosis) occurred in 50 patients (25%). Five variables were individually associated with a higher risk of restenosis: recurrent angina (p = 0.0002), exercise-induced angina (p = 0.0001), a positive treadmill test (p = 0.008), more exercise ST deviation (p = 0.04) and a lower maximum exercise heart rate (p = 0.05). However, only exercise-induced angina (p = 0.002), recurrent angina (p = 0.01) and a positive treadmill test (p = 0.04) were independent predictors of restenosis. Using these 3 variables, patient subsets could be identified with restenosis rates ranging from 11 to 83%. The exercise treadmill test added independent information to symptom status about the risk of restenosis after elective PTCA. Nevertheless, 20% of patients with restenosis had neither recurrent angina nor exercise-induced ischemia at follow-up. For more accurate detection of restenosis, the exercise treadmill test must be supplemented by a more definitive test.

Angiography

Brachial approach to emergency cardiac catheterization during thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

The use of the brachial approach to acute coronary intervention has not been previously studied. In the course of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials, we used the transbrachial approach to cardiac catheterization with or without angioplasty in 202 of 704 (28.6%) patients. The baseline characteristics of age, sex, risk factors, medical history, time from symptom onset to therapy, and left ventricular function were similar for the 2 different approaches. Time from therapy to coronary angiography was not delayed by the brachial approach compared with the femoral approach: 97.1 +/- 26 min vs. 99.9 +/- 133.8 min, respectively. Chemical patency was established in 78 vs. 73% of patients and technical success with acute PTCA with the brachial approach was 89% vs. 78% with the femoral approach. Clinical outcomes were quite similar with respect to death (6 vs. 6%), reocclusion (10 vs. 14%), and emergency coronary bypass surgery (5 vs. 6%). Baseline hematocrit was 43.9 +/- 4.4 and 43.5 +/- 4.8, respectively with a nadir of 32.9 +/- 5.6 vs. 33.0 +/- 5.4. The need for vascular repair occurred in 1% vs. 3% of patients and retroperitoneal hemorrhage was documented in 1% vs. 1% of patients. This study indicates that in the hands of experienced operators the transbrachial approach to acute coronary intervention in the acute phase of treatment with thrombolytic therapy can be used with equal risks and efficacy as the femoral approach.

Aged

Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and long-term prognosis.

Thirteen (1.8%) of 708 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I, II and III trials developed a stroke. Four strokes were hemorrhagic and nine were nonhemorrhagic. Of five prespecified risk factors for intracranial hemorrhage (age greater than 65 years, history of hypertension, history of prior cerebrovascular disease, aspirin use and acute hypertension), two patients had two risk factors and one patient had one risk factor. However, 80% of patients without intracranial hemorrhage had at least one risk factor and 31% had two risk factors. No patient with a prior stroke or transient ischemic attack (all greater than 6 months previously) had an intracranial hemorrhage. Of three prespecified risk factors for nonhemorrhagic stroke (atrial fibrillation, prior cerebrovascular disease and large anterior wall infarction), only the occurrence of a large anterior myocardial infarction (with ejection fraction less than 45%) was a predictor (p = 0.0015). The in-hospital death rate was 25% for patients with hemorrhagic stroke versus 11% for patients with a non-hemorrhagic stroke and 6% for those patients without a stroke. Furthermore, the hospital stay was greater than 50% longer in patients who had a stroke than in those who did not. Thus, intracranial hemorrhage remains an unpredictable risk in patients treated with thrombolytic therapy and cerebral infarction is related to anterior myocardial infarction and poor left ventricular function. Both types of stroke are associated with substantial morbidity and mortality.

Aged

Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty.

Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy.

Angioplasty, Balloon, Coronary

Repeat percutaneous transluminal coronary angioplasty and predictors of recurrent restenosis.

One hundred seventeen consecutive patients undergoing repeat percutaneous transluminal coronary angioplasty (PTCA) were studied to assess procedural success and recurrent restenosis rates. Clinical, anatomic and procedural variables were examined as predictors of recurrent restenosis using stepwise logistic regression analysis. Primary success was achieved in 114 patients (97.5%). One patient (0.8%) died after acute occlusion. No other in-hospital complications were encountered. After a mean follow-up interval of 218 +/- 160 days, 72 of 114 successfully dilated patients (63%) remained angina free. There were no late deaths. Three patients (2.6%) experienced a late myocardial infarction. Follow-up arteriography was performed in 100 patients (88%), of whom 32% had recurrent restenosis (greater than 50% luminal diameter narrowing). On univariate analysis, the presence of 3 clinical variables at repeat PTCA was associated with significantly higher recurrent restenosis rates compared with their absence, that is, unstable angina (48 vs 20%, p = 0.003), diabetes (61 vs 26%, p = 0.003) and hypertension (46 vs 18%, p = 0.003). Patients with recurrent restenosis had a shorter interval between first and second PTCA compared with those who remained patent (136 +/- 116 vs 214 +/- 163 days, p = 0.018). Multivariate analysis confirmed unstable angina, diabetes and hypertension as independent predictors of recurrent restenosis. Repeat PTCA may be performed for restenosis with a high likelihood of success and low incidence of complications. The rate of recurrent restenosis is similar to that reported for initial angioplasty. Patients with unstable angina, diabetes and hypertension appear to be at higher risk for recurrent restenosis.

Aged

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: results of a multicenter trial. TAMI Study Group.

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon

Correlation of clinical history with quantitative histology of lower extremity atheroma biopsies obtained with the Simpson atherectomy catheter.

The purpose of this study was to compare the histologic variability of atheromas resected from patients with various risk factors for vascular disease. Twenty-seven plaques obtained using the Simpson atherectomy catheter were studied. The results of this light and electron microscopic study indicate that patients with diabetes mellitus had increased numbers of smooth muscle cells in their plaques (P less than 0.05) and a trend toward denser, less fatty connective tissue matrix (P less than 0.07) when compared with non-diabetics, and that female diabetics had more smooth muscle cells in their plaques than male diabetics (P less than 0.05). The female patients, regardless of risk factors, had more smooth muscle cells in their plaques than male patients (P less than 0.004). Patients with poor distal runoff had more neovascularization of plaque (P less than 0.001). Tobacco use and age did not have statistically significant correlations with histologic patterns.

Arteriosclerosis

Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-1) trial: influence of infarct location on arterial patency, left ventricular function and mortality.

The influence of infarct location on arterial patency, left ventricular function and mortality after 150 mg of intravenous recombinant tissue-type plasminogen activator (rt-PA) and selective coronary angioplasty was studied in 386 patients with acute myocardial infarction. In 329 patients with acute and 1 week angiograms, the 90 min infarct-related artery patency rate after rt-PA in the left anterior descending, the left circumflex and the right coronary artery was 77, 68 and 68%, respectively. Angioplasty, performed in half the patients, resulted in a final acute patency rate of 93%, which was not related to arterial distribution. Repeat catheterization and revascularization were required in 12% of patients before day 7 and were independent of arterial distribution. The reocclusion rate for the right coronary artery (21%) was higher than that for the left anterior descending (12%) or left circumflex (5%) artery (p = 0.01). Acute and 1 week contrast ventriculograms suitable for analysis were available in 266 patients. Whereas serial left ventricular ejection fraction did not improve during the course of this study, serial regional wall motion (centerline chord method) improved in each arterial distribution. The in-hospital mortality rate of 6% was not related to arterial distribution, although death was twice as likely with proximal compared with distal lesions. Ten of 11 patients who died in the group with the left anterior descending artery as the infarct-related artery had a lesion proximal to the first septal perforator branch.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

New interventional technologies in cardiology.

If atherectomy procedures are found to be safe and effective for removal of plaque in human coronary arteries, they can be expected to provide an important alternative to balloon angioplasty for the treatment of many types of coronary lesions. In addition, many patients who are candidates for coronary artery bypass procedures could likely benefit from these less invasive procedures. Although atherectomy has a theoretic potential for reducing the rate of restenosis by removing the plaque rather than pushing it to the side, it is unlikely to eliminate the restenosis problem completely. A more important advantage of atherectomy may be the potential for successful treatment of lesions that are anatomically unsuitable for PTCA. Even though balloon catheter technology has evolved to the point that almost all lesions in the coronary anatomy can be successfully negotiated, approximately half the coronary patients who require invasive therapy in the United States are still undergoing open-heart bypass procedures. Thus, if atherectomy can expand the indications for interventional therapy to the types of lesions that are currently considered unsuitable for PTCA, the large number of patients who are currently unable to benefit from interventional catheterization techniques could be treated. With all the new devices under investigation, carefully controlled prospective randomized trials must be conducted once the developmental phases have been completed. Each new technology must be compared with the current state-of-the-art techniques of balloon angioplasty and coronary artery bypass operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon

Prognostic implications and predictors of enhanced regional wall motion of the noninfarct zone after thrombolysis and angioplasty therapy of acute myocardial infarction. The TAMI Study Groups.

Although impairment of left ventricular function in acute myocardial infarction is closely related to extent of necrosis, function in the noninfarct zone also contributes to global performance and thus may be of prognostic importance. We evaluated left ventricular regional wall motion by the centerline chord method in 332 patients treated with intravenous tissue-type plasminogen activator (t-PA) in the multicenter Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. All patients had acute contrast ventriculograms of suitable quality for analysis, and 266 patients had paired acute and day 7 ventriculograms. Enhanced function of the noninfarct zone was present during acute catheterization (+0.3 SD/chord) and was associated with preservation of the acute ejection fraction (p = 0.0001). Multiple linear regression analysis revealed the most powerful clinical factor associated with enhanced function of the noninfarct zone was the absence of multivessel disease (p = 0.0001). Clinical factors that were related weakly to noninfarct zone function included female gender (p = 0.08) and higher flow in the infarct artery (p = 0.03). Neither the degree of infarct zone dysfunction nor infarct location was associated with hyperkinesis of the noninfarct zone. In hospital, mortality was closely related to function in the noninfarct zone (p = 0.006), ejection fraction (p = 0.025), and the number of diseased vessels (p = 0.009) but was not related to infarct zone function (p = 0.128).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon

Exercise treadmill testing is a poor predictor of anatomic restenosis after angioplasty for acute myocardial infarction.

This study evaluated whether an exercise treadmill test could predict restenosis in 289 patients 6 months after a successful emergency angioplasty of the infarct-related artery for acute myocardial infarction. After excluding those with interim interventions (64), medical events (36), or medical contraindications to follow-up testing (25), both a treadmill test and a cardiac catheterization were completed in 144 patients, 88% of those eligible for this assessment. Four patients with left bundle branch block or pacemaker rhythm at the time of treadmill testing were also excluded from analysis. Of six follow-up clinical and treadmill variables examined by multivariable logistic regression analysis, only exercise ST deviation was independently correlated with restenosis at follow-up (chi 2 = 5, p = 0.02). The clinical diagnosis of angina at follow-up, although marginally related to restenosis when considered by itself (p = 0.04), did not add significant information once ST deviation was known. The sensitivity of ST deviation of 0.10 mV or greater for detecting restenosis was only 24% (13 of 55 patients), and the specificity was 88% (75 of 85 patients). The sensitivity of exercise-induced ST deviation for detection of restenosis was not affected by extent or severity of wall motion abnormalities at follow-up, by the timing of thrombolytic therapy or of angioplasty, or by the presence of collateral blood flow at the time of acute angiography. A second multivariable analysis evaluating the association of the same variables with number of vessels with significant coronary disease at the 6-month catheterization found an association with both exercise ST deviation (p = 0.003) and exercise duration (p = 0.04). Angina symptoms and exercise treadmill test results in this population had limited value for predicting anatomic restenosis 6 months after emergency angioplasty for acute myocardial infarction.

Angina Pectoris